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Li J, Zhou J, Li P, Wang Y, Ridderhof N, Al-Tawfiq JA, Brouwer WP, Chen K, de Knegt RJ, Peppelenbosch MP, Hansen BE, Engel MF, Zheng MH, Memish ZA, Eslam M, Janssen HLA, Pan Q, Ayada I. The global prevalence and impact of steatotic liver disease and viral infections: A systematic review and meta-analysis. Hepatol Commun 2025; 9:e0689. [PMID: 40227096 PMCID: PMC11999411 DOI: 10.1097/hc9.0000000000000689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 01/22/2025] [Indexed: 04/15/2025] Open
Abstract
BACKGROUND Steatotic liver disease (SLD) affects ~30% of adults worldwide. The global population is continuously threatened by epidemic and endemic viral diseases. This study aims to thoroughly examine the interaction between SLD and major viral diseases. METHODS We systematically searched databases from inception to April 2, 2024, for observational studies recording viral-infected adult patients with eligible data on the presence of hepatic steatosis. RESULTS Six hundred thirty-six eligible studies were included in the analysis of SLD prevalence. Among patients with monoinfections, the highest SLD prevalence was observed in those infected with HCV at 49% (95% CI: 47%-51%), followed by SARS-CoV-2 (39%, 95% CI [34%-44%]), HIV (39%, 95% CI [33%-44%]), and HBV (36%, 95% CI [32%-40%]). Additionally, co-infections, such as HCV-HIV and HBV-HCV, exhibit even higher SLD prevalence. The prevalence of steatohepatitis is particularly high in HIV-infected (24%, 95% CI: 17%-30%) and HCV-infected (18%, 95% CI: 13%-24%) populations. The co-existence of SLD with viral infections was associated not only with the progression of liver disease but also with more severe outcomes of the infections and poorer responses to antiviral treatment. The combination of cardiometabolic risk factors and viral-associated and host factors contributes to the higher risk of SLD in viral-infected populations. CONCLUSIONS SLD is highly prevalent in viral-infected populations, and the reciprocal interactions between SLD and viral diseases exacerbate both conditions, leading to poorer patient outcomes in general.
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Affiliation(s)
- Jiajing Li
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jiahua Zhou
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Pengfei Li
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Yining Wang
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Nathalie Ridderhof
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jaffar A. Al-Tawfiq
- Infectious Disease Unit, Specialty Internal Medicine, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
- Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland, USA
| | - Willem Pieter Brouwer
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Kan Chen
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Robert J. de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Maikel P. Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bettina E. Hansen
- Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Maarten F.M. Engel
- Medical Library, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Ming-Hua Zheng
- Department of Hepatology, MAFLD Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
| | - Ziad A. Memish
- College of Medicine, Al Faisal University, Riyadh, Saudi Arabia
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, USA
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia
| | - Harry L. A. Janssen
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
- Toronto Center for Liver Disease, Toronto General Hospital, University of Toronto, Ontario, Canada
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Ibrahim Ayada
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
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McCary A, Sheu YS, Chesbrough K, Jonas MC. Improved Liver Fibrosis Regression After Direct-Acting Antiviral Therapy in Hepatitis C Patients: A Comparison of Patients With and Without MASLD. Clin Ther 2025:S0149-2918(25)00087-6. [PMID: 40287335 DOI: 10.1016/j.clinthera.2025.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 03/12/2025] [Accepted: 03/23/2025] [Indexed: 04/29/2025]
Abstract
PURPOSE Chronic Hepatitis C (CHC) often results in liver fibrosis. Therefore, an important benefit of CHC treatment with direct-acting antiviral (DAA) medication is liver fibrosis regression. However, it is unclear how concurrent liver steatosis affects fibrosis regression following DAA therapy. Recent guidelines have defined liver steatosis associated with metabolic syndrome as metabolic dysfunction-associated steatotic liver disease (MASLD). We sought to examine the association of MASLD with the fibrosis regression benefits of DAA treatment for CHC. METHODS We conducted an observational retrospective analysis using electronic health records of patients aged 18-65 who completed DAA therapy for CHC from 2016 through 2022. FIB-4 scores were calculated during three time periods: just prior to DAA initiation, within 6 months post-DAA completion, and within 6-12 months post-DAA completion. These scores categorized liver fibrosis as high risk (>3.25), intermediate risk (1.45-3.25), or low risk (<1.45). An ordinal logistic regression model assessed the degree of fibrosis regression across these periods in CHC patients with and without MASLD. FINDINGS We identified 845 patients with CHC who received DAA therapy, of whom 225 met MASLD criteria. Both CHC patients with and without MASLD exhibited a decrease in FIB-4 category (coefficient = -0.361, P < 0.001) within the year following DAA therapy. The reduction in FIB-4 category post-treatment was more pronounced in the MASLD group compared to the non-MASLD group, as evidenced by a significant interaction between group and time period (coefficient = -0.439, P = 0.004). IMPLICATIONS In our cohort, MASLD was associated with greater liver fibrosis regression in the year following DAA therapy for CHC. This suggests that the concurrent presence of MASLD is not associated with diminished fibrosis regression from DAA therapy. Additional research is needed to determine the exact mechanism responsible for DAA-associated fibrosis regression in patients with MASLD.
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Affiliation(s)
- Alexis McCary
- Department of Gastroenterology, Mid-Atlantic Permanente Medical Group, Upper Marlboro, Maryland; Mid-Atlantic Permanente Research Institute, Mid-Atlantic Permanente Medical Group, Washington, District of Columbia.
| | - Yi-Shin Sheu
- Mid-Atlantic Permanente Research Institute, Mid-Atlantic Permanente Medical Group, Washington, District of Columbia
| | - Karen Chesbrough
- Mid-Atlantic Permanente Research Institute, Mid-Atlantic Permanente Medical Group, Washington, District of Columbia
| | - M Cabell Jonas
- Mid-Atlantic Permanente Research Institute, Mid-Atlantic Permanente Medical Group, Washington, District of Columbia
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Tang Y, Deng Y, Zhang G, Wang Y, Wang J, Wu J, Gu M. Inflammatory markers as predictors of liver fibrosis in type 2 diabetes patients with metabolic dysfunction-associated fatty liver disease. Front Endocrinol (Lausanne) 2025; 16:1556646. [PMID: 40265164 PMCID: PMC12011603 DOI: 10.3389/fendo.2025.1556646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Accepted: 03/11/2025] [Indexed: 04/24/2025] Open
Abstract
Objective This study investigates the link between inflammatory markers and liver fibrosis in type 2 diabetes mellitus (T2DM) patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods From Oct 2020 to Oct 2024, 769 hospitalized T2DM patients were studied. They were split into Control (n=389) and Experimental groups (T2DM with MAFLD, n=380). The Experimental group was further divided based on FIB-4 scores into non-fibrosis (FIB-4< 1.3, n=267), suspected fibrosis (1.3 ≤ FIB-4 ≤ 2.67, n=99), and advanced fibrosis (FIB-4 > 2.67, n=14). Logistic regression identified factors affecting liver fibrosis, while ROC analysis assessed the predictive value of NLR, SIRI, PLR, and PHR for liver fibrosis in T2DM-MAFLD patients. Results The Experimental group showed higher BMI, FPG, TG, TC, LDL-C, ALT, AST, ALB, GGT, and SUA, but lower age, diabetes duration, MPV, and HDL-C (P< 0.05). Compared to non-fibrosis, suspected fibrosis had higher age, diabetes duration, MPV, AST, and NLR, and lower LY, PLR, PHR. Advanced fibrosis featured higher age, AST, NLR, FPG, HbA1c, SIRI, and lower LY, RBC, LDL-C, PLR, PHR, Hb, PLT, and ALB (P< 0.05). Logistic regression identified NLR, SIRI, PLR, and PHR as significant factors for liver fibrosis. ROC analysis showed AUCs of 0.712 (NLR), 0.757 (SIRI), 0.703 (PLR), and 0.806 (PHR) with sensitivities and specificities varying among markers. Optimal cut-offs were 1.573 (NLR), 1.465 (SIRI), 110.819 (PLR), and 185.379 (PHR). Conclusions NLR, SIRI, PLR, and PHR significantly influence liver fibrosis in T2DM patients with MAFLD, aiding in its diagnosis and management.
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Affiliation(s)
- Yange Tang
- Department of Endocrinology, Hebei Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Yulong Deng
- Department of Orthopaedics and Traumatology, Hebei Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Gengliang Zhang
- Department of Endocrinology, Hebei Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Yanjun Wang
- Department of Endocrinology, Hebei Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Jing Wang
- Department of Endocrinology, Hebei Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Jie Wu
- Department of Endocrinology, Hebei Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Mengjin Gu
- Department of Anesthesiology, Zhengding County People’s Hospital, Shijiazhuang, China
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Tada T, Kumada T, Gotoh T, Niwa F, Ogawa S, Yasuda S, Koshiyama Y, Akita T, Tanaka J, Kodama Y, Toyoda H. Validation of a B-mode ultrasonography scoring system for assessing liver steatosis: A comparison with MRI-Derived proton density fat fraction. Hepatol Res 2025. [PMID: 40318112 DOI: 10.1111/hepr.14190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/10/2025] [Accepted: 03/18/2025] [Indexed: 05/07/2025]
Abstract
AIM Noninvasive detection of liver steatosis and monitoring its progression are essential for effective therapeutic management. We validated the diagnostic performance of an ultrasonography (US)-based steatotic liver scoring system, derived from the B-mode method and the hepatic steatosis index (HSI) for the detection of liver steatosis, as identified by proton density fat fraction (PDFF) measurements on magnetic resonance imaging (MRI). METHODS A total of 916 patients with chronic liver disease were included in the analysis. RESULTS The median MRI-PDFF value was 4.0% (interquartile range: 2.0-9.7). The distribution of scores (0/1/2/3/4/5/6) according to the US-based steatotic liver scoring system was as follows: 475, 36, 99, 78, 141, 66, and 21, respectively. The median HSI was 32.8 (28.9-37.4). A significant positive association between advancing scores of the US-based steatotic liver scoring system and increasing MRI-PDFF values was observed (p < 0.001). The diagnostic performance of the US-based steatotic liver scoring system and HSI for detecting steatosis grades ≥1, ≥2, and 3, as determined by MRI-PDFF, showed areas under the receiver operating characteristic curve of 0.940 and 0.842 (p < 0.001), 0.949 and 0.847 (p < 0.001), and 0.945 and 0.864 (p < 0.001), respectively. When the cutoff values of the scoring system were set at 2, 3, and 4 for steatosis grades ≥1, ≥2, and 3, the sensitivity and specificity were 90.6% and 90.5%, 92.9% and 83.0%, and 93.3% and 84.0%, respectively. CONCLUSION The B-mode US-based steatotic liver scoring system demonstrated robust diagnostic capability in detecting liver steatosis.
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Affiliation(s)
- Toshifumi Tada
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takashi Kumada
- Gifu Kyoritsu University, Ogaki, Japan
- Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tatsuya Gotoh
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Japan
| | - Fumihiko Niwa
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Japan
| | - Sadanobu Ogawa
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yuichi Koshiyama
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Tomoyuki Akita
- Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Junko Tanaka
- Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
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Liao H, He YJ, Zhang S, Kang X, Yang X, Xu B, Magnuson JT, Wang S, Zheng C, Qiu W. Perfluorohexanesulfonic Acid (PFHxS) Induces Hepatotoxicity through the PPAR Signaling Pathway in Larval Zebrafish ( Danio rerio). ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58:22894-22906. [PMID: 39680074 DOI: 10.1021/acs.est.4c07056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2024]
Abstract
In recent years, the industrial substitution of long-chain per- and polyfluoroalkyl substances (PFAS) with short-chain alternatives has become increasingly prevalent, resulting in the widespread environmental detection of perfluorohexanesulfonic acid (PFHxS), a short-chain PFAS. However, there remains limited information about the potential adverse effects of PFHxS at environmental concentrations to wildlife. Here, early life stage zebrafish (Danio rerio) were exposed to environmentally relevant concentrations of PFHxS to better characterize the adverse effects of PFHxS on aquatic organisms. Nontargeted, transcriptomic analysis revealed potential hepatotoxic effects in exposed larvae, including macrovesicular and microvesicular hepatic steatosis, as well as focal liver necrosis. Morphological, histological, biochemical, and targeted transcript expression profiles further confirmed significant alterations in hepatocellular lesion numbers, liver pathological structures, relative liver size, liver biochemical parameters, and liver function genes. To validate the PPAR-mediated toxicological mechanism identified as an enriched pathway through in silico bioinformatics analysis, we tested the coexposure to an antagonist and PPAR morpholino knockdown. This intervention alleviated PFHxS-induced hepatic effects, including reductions in the levels of aspartate aminotransferase, alanine aminotransferase, total cholesterol, and total triglycerides. Our results demonstrate that environmentally relevant concentrations of PFHxS can impair liver development and function in fish, which could have potential risks to aquatic organisms.
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Affiliation(s)
- Haolin Liao
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China
- School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen 518055, China
| | - Ying-Jie He
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China
| | - Shuwen Zhang
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China
- Eastern Institute for Advanced Study, Eastern Institute of Technology, Ningbo 315200, China
| | - Xinyuan Kang
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China
| | - Xin Yang
- Shenzhen Key Laboratory of Precision Measurement and Early Warning Technology for Urban Environmental Health Risks, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China
| | - Bentuo Xu
- National and Local Joint Engineering Research Center of Ecological Treatment Technology for Urban Water Pollution, School of Life and Environmental Science, Wenzhou University, Chashan University Town, Wenzhou 325035, China
| | - Jason T Magnuson
- U.S. Geological Survey, Columbia Environmental Research Center, Columbia, Missouri 65201, United States
| | - Shuping Wang
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China
| | - Chunmiao Zheng
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China
- Eastern Institute for Advanced Study, Eastern Institute of Technology, Ningbo 315200, China
| | - Wenhui Qiu
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China
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Yuan C, Zhang C, Geng X, Feng C, Su Y, Wu Y, Wang Y, Chen L, Ding Q, Voortman T, Wang H, Zong G. Associations of an overall healthy lifestyle with the risk of metabolic dysfunction-associated fatty liver disease. BMC Public Health 2024; 24:3264. [PMID: 39587552 PMCID: PMC11587751 DOI: 10.1186/s12889-024-20663-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 11/07/2024] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) affects up to one-third of the global population. Since no approved pharmacotherapy for MAFLD is available, lifestyle modification remains the cornerstone of clinical care. Our study aims to evaluate the association of an overall healthy lifestyle with MAFLD risk. METHODS We conducted an analysis of 327,387 participants from UK biobank. An overall healthy lifestyle score including six evidence-based lifestyles (diet, alcohol consumption, physical activity, sedentary behavior, sleep, and smoking) was assessed by questionnaires. MAFLD and its subtypes were diagnosed by blood biochemistry, ICD codes, and medication information from touchscreen and verbal interview. The prevalence ratios (PRs) and risk ratios (RRs) were estimated by Poisson regression models with robust variance. RESULTS In the cross-sectional analysis, the PR (95% CI) was 0.83 (0.83 to 0.84) for MAFLD, and 0.83 (0.83 to 0.84) for MAFLD-overweight/obesity (MAFLD-O), 0.68 (0.66 to 0.70) for MAFLD-lean/normal weight and metabolic dysfunction (P-value for heterogeneity < 0.001), and 0.71 (0.71 to 0.72) for MAFLD-type 2 diabetes mellitus (MAFLD-T2D); and 0.68 (0.66 to 0.71) for dual (or more) etiology fatty liver disease (MAFLD-dual) and 0.83 (0.83 to 0.84) for single etiology MAFLD (MAFLD-single) (P-value for heterogeneity < 0.001) for one additional point in the overall healthy lifestyle score. During a median follow-up of 4.4 years, the RR (95% CI) was 0.83 (0.81 to 0.85) for MAFLD, and 0.83 (0.81 to 0.85) for MAFLD-O, 0.71 (0.62 to 0.81) for MAFLD-L, and 0.68 (0.64 to 0.72) for MAFLD-T2D (P-value for heterogeneity < 0.001); and 0.83 (0.81 to 0.85) for MAFLD-dual and 0.70 (0.58 to 0.85) for MAFLD-single (P-value for heterogeneity = 0.08) for one additional point in the overall healthy lifestyle score. These findings were validated in a prospective analysis among 15,721 participants with revisit data, and also supported by fatty liver index and proton density fat fraction data. CONCLUSIONS An overall healthy lifestyle that includes six evidence-based factors was strongly associated with lower MAFLD risk, especially the subtypes with multiple etiologies.
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Affiliation(s)
- Caimei Yuan
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, PR China
| | - Chengjing Zhang
- Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China
| | - Xin Geng
- Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China
- National Center for Liver Cancer, Naval Medical University, Shanghai, 200438, China
- Ministry of Education (MOE) Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Naval Medical University, Shanghai, 200438, China
| | - Chengwu Feng
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, PR China
| | - Yang Su
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, PR China
| | - Yinfan Wu
- Department of clinical nutrition, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200081, China
| | - Ying Wang
- Department of clinical nutrition, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200081, China
| | - Li Chen
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, PR China
| | - Qiurong Ding
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, PR China
| | - Trudy Voortman
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, 3000 CA, The Netherlands
| | - Hongyang Wang
- Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China.
- National Center for Liver Cancer, Naval Medical University, Shanghai, 200438, China.
- Ministry of Education (MOE) Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Naval Medical University, Shanghai, 200438, China.
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, 225 Changhai Road, Shanghai, 200438, PR China.
| | - Geng Zong
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, PR China.
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
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Gonzalez-Aldaco K, Torres-Reyes LA, Ojeda-Granados C, Leal-Mercado L, Roman S, Panduro A. Metabolic Dysfunction-Associated Steatotic Liver Disease in Chronic Hepatitis C Virus Infection: From Basics to Clinical and Nutritional Management. Clin Pract 2024; 14:2542-2558. [PMID: 39585028 PMCID: PMC11587073 DOI: 10.3390/clinpract14060200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 11/19/2024] [Accepted: 11/20/2024] [Indexed: 11/26/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity and other cardiometabolic risk factors. MASLD has rapidly become the most common cause of liver disease worldwide, currently affecting 38% of the global population. Excess weight causes chronic inflammation and the activation of different pathways involved in liver damage. MASLD can progress from simple steatosis to steatohepatitis, giving way to its inflammatory component, metabolic dysfunction-associated steatohepatitis (MASH), previously recognized as non-alcoholic steatosis hepatitis (NASH). Chronic hepatitis C virus (HCV) infection remains a significant challenge to liver health as it triggers hepatic inflammation, metabolic disruption, and hepatic steatosis. The convergence of MASLD and chronic HCV infection can significantly alter the course of liver disease and accelerate the progression to severe liver damage. Currently, HCV treatment has a high cure rate. However, in patients who achieve a sustained virological response after treatment with direct-acting antivirals, weight gain, and excessive calorie intake may contribute to increased liver steatosis and a higher risk of liver disease progression. Therefore, the effective clinical and nutritional management of HCV patients, both before and after viral eradication, is crucial to reducing the risk of death from hepatocellular carcinoma. Understanding the complex interactions between MASLD and HCV infection is crucial for managing these patients appropriately. Herein, host and viral mechanisms inducing liver damage during the coexistence of MASLD and HCV infection are described, and their therapeutic and dietary management are discussed.
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Affiliation(s)
- Karina Gonzalez-Aldaco
- Centro Universitario de los Valles, Universidad de Guadalajara, Carretera Guadalajara-Ameca Km. 45.5, Ameca 46600, Jalisco, Mexico;
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Hospital #278, Col. El Retiro, Guadalajara 44280, Jalisco, Mexico; (L.L.-M.); (S.R.); (A.P.)
| | - Luis A. Torres-Reyes
- Centro Universitario de los Valles, Universidad de Guadalajara, Carretera Guadalajara-Ameca Km. 45.5, Ameca 46600, Jalisco, Mexico;
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Hospital #278, Col. El Retiro, Guadalajara 44280, Jalisco, Mexico; (L.L.-M.); (S.R.); (A.P.)
| | - Claudia Ojeda-Granados
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, 95123 Catania, Italy;
| | - Leonardo Leal-Mercado
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Hospital #278, Col. El Retiro, Guadalajara 44280, Jalisco, Mexico; (L.L.-M.); (S.R.); (A.P.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Sonia Roman
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Hospital #278, Col. El Retiro, Guadalajara 44280, Jalisco, Mexico; (L.L.-M.); (S.R.); (A.P.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Arturo Panduro
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Hospital #278, Col. El Retiro, Guadalajara 44280, Jalisco, Mexico; (L.L.-M.); (S.R.); (A.P.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
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Selvamani SP, Khan A, Tay ESE, Garvey M, Ajoyan H, Diefenbach E, Gloss BS, Tu T, George J, Douglas MW. Hepatitis B Virus and Hepatitis C Virus Affect Mitochondrial Function Through Different Metabolic Pathways, Explaining Virus-Specific Clinical Features of Chronic Hepatitis. J Infect Dis 2024; 230:e1012-e1022. [PMID: 38655824 PMCID: PMC11566039 DOI: 10.1093/infdis/jiae210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 04/15/2024] [Accepted: 04/20/2024] [Indexed: 04/26/2024] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) and hepatitis B virus (HBV) cause chronic hepatitis with important clinical differences. HCV causes hepatic steatosis and insulin resistance, while HBV confers increased risk of liver cancer. We hypothesized these differences may be due to virus-specific effects on mitochondrial function. METHODS Seahorse technology was used to investigate effects of virus infection on mitochondrial function. Cell-based assays were used to measure mitochondrial membrane potential and quantify pyruvate and lactate. Mass spectrometry was performed on mitochondria isolated from HBV-expressing, HCV-infected, and control cells cultured with isotope-labelled amino acids, to identify proteins with different abundance. Altered expression of key mitochondrial proteins was confirmed by real-time polymerase chain reaction (PCR) and western blot. RESULTS Reduced mitochondrial function and ATP production were observed with HCV infection and HBV expression. HCV impaired glycolysis and fatty acid oxidation, promoting lipid accumulation whereas HBV caused lactate accumulation. In HBV-expressing cells enrichment of pyruvate dehydrogenase kinase inhibited pyruvate to acetyl-CoA conversion thereby reducing its availability for mitochondrial oxidative phosphorylation. CONCLUSIONS HBV and HCV impair mitochondrial function. HCV infection reduces lipid oxidation causing its accumulation and fatty liver disease. HBV infection affects pyruvate processing causing lactate accumulation, cellular stress, and increased risk of liver disease and cancer.
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Affiliation(s)
- Sakthi Priya Selvamani
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
| | - Anis Khan
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
| | - Enoch S E Tay
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
| | - Matthew Garvey
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
| | - Harout Ajoyan
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
| | - Eve Diefenbach
- Protein Core Facility, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia
| | - Brian S Gloss
- Westmead Research Hub, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia
| | - Thomas Tu
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
| | - Jacob George
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
| | - Mark W Douglas
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
- Centre for Infectious Diseases and Microbiology, Sydney Infectious Diseases Institute, The University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
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9
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Cheng Y, Song Z, Liu Y, Xu X, Zhang D, Zou Y, Liu L, Zeng Y, Li W, Bai D, Dai D. Common molecular basis for MASH and hepatitis C revealed via systems biology approach. Front Oncol 2024; 14:1442221. [PMID: 39605886 PMCID: PMC11599856 DOI: 10.3389/fonc.2024.1442221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Accepted: 10/16/2024] [Indexed: 11/29/2024] Open
Abstract
Background Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by liver inflammation and damage caused by a buildup of fat in the liver. Hepatitis C, caused by hepatitis C virus (HCV), is a disease that can lead to liver cirrhosis, liver cancer, and liver failure. MASH and hepatitis C are the common causes of liver cirrhosis and hepatocellular carcinoma. Several studies have shown that hepatic steatosis is also a common histological feature of liver in HCV infected patients. However, the common molecular basis for MASH and hepatitis C remains poorly understood. Methods Firstly, differentially expressed genes (DEGs) for MASH and hepatitis C were extracted from the GSE89632, GSE164760 and GSE14323 datasets. Subsequently, the common DEGs shared among these datasets were determined using the Venn diagram. Next, a protein-protein interaction (PPI) network was constructed based on the common DEGs and the hub genes were extracted. Then, gene ontology (GO) and pathway analysis of the common DEGs were performed. Furthermore, transcription factors (TFs) and miRNAs regulatory networks were constructed, and drug candidates were identified. After the MASH and hepatitis C cell model was treated with predicted drug, the expression levels of the signature genes were measured by qRT-PCR and ELISA. Results 866 common DEGs were identified in MASH and hepatitis C. The GO analysis showed that the most significantly enriched biological process of the DEGs was the positive regulation of cytokine production. 10 hub genes, including STAT1, CCL2, ITGAM, PTPRC, CXCL9, IL15, SELL, VCAM1, TLR4 and CCL5, were selected from the PPI network. By constructing the TF-gene and miRNA-gene network, most prominent TFs and miRNAs were screened out. Potential drugs screening shows that Budesonide and Dinoprostone may benefit patients, and cellular experiments showed that Budesonide effectively inhibited the expression of genes related to glycolipid metabolism, fibrosis, and inflammatory factors. Conclusion We extracted 10 hub genes between MASH and hepatitis C, and performed a series of analyses on the genes. Molecular docking and in vitro studies have revealed that Budesonide can effectively suppress the progression of MASH and hepatitis C. This study can provide novel insights into the potential drug targets and biomarkers for MASH and hepatitis C.
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Affiliation(s)
- Yongwei Cheng
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Zihao Song
- GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, Guangzhou, China
| | - Ye Liu
- School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Xichao Xu
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Dali Zhang
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Yigui Zou
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Liang Liu
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Yinzhen Zeng
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Wenwen Li
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Daming Bai
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
| | - Dongling Dai
- Key Laboratory for Precision Diagnosis and Treatment of Pediatric Digestive System Diseases, Endoscopy Center and Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen, China
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Xie S, Yan J, Fu X, Yu G, Yan X, Yang F, Li B. Hepatitis C virus subtype distribution and resistance-associated substitutions in high-risk population groups in Guangdong Province, China. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2024; 123:105653. [PMID: 39111345 DOI: 10.1016/j.meegid.2024.105653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 07/21/2024] [Accepted: 08/02/2024] [Indexed: 08/16/2024]
Abstract
OBJECTIVE In Guangdong Province, hepatitis C virus (HCV) had been found to confer resistance to direct-acting antivirals (DAAs). There were few studies of HCV subtypes and resistance-associated substitutions (RASs) of HCV in different high-risk populations. In this study, we aimed to determine the subtype distribution and the RASs in high-risk population groups, including drug users (DU), men who have sex with men (MSM), female sex workers (FSW), and male patients with sexually transmitted diseases (STD) in Guangdong Province (a highly developed province with a large population). METHODS Using a city-based sampling strategy,1356 samples were obtained from different population groups. Phylogenetic analyses determined subtypes based on Core, NS5B, or NS5A sequences. HCV subtype distribution and RASs in various risk groups and regions were analyzed. RESULTS Ten subtypes, of which 6 h and 6 k were novel in Guangdong, were identified. The primary subtype among all risk groups was 6a. RASs in 1b and 3a were different from those observed in other studies. Subtype 3b in western Guangdong was higher than the other three regions. No RASs were found in 6a or any other genotype 6. CONCLUSIONS The HCV subtypes are expanding in high-risk populations in Guangdong. Drug use by other risk groups and commercial sex by DU may bridge the dissemination of 6a from DU to other populations. The RAS profiles of 1b and 3a differed from those reported in studies conducted in southwestern China. Further research is required to determine the reason for this discrepancy. Moreover, the combination of RASs was high in subtype 3b. To guide HCV treatment of subtype 3b, pretreatment subtyping of HCV genotype 3 should be considered in western cities in the near future.
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Affiliation(s)
- Shilan Xie
- Institute of HIV/AIDS Prevention, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, Guangdong, China
| | - Jin Yan
- Institute of Pathogenic Microorganism, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, Guangdong, China.
| | - Xiaobing Fu
- Institute of HIV/AIDS Prevention, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, Guangdong, China
| | - Guolong Yu
- Institute of Pathogenic Microorganism, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, Guangdong, China
| | - Xinge Yan
- Institute of Pathogenic Microorganism, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, Guangdong, China
| | - Fang Yang
- Institute of HIV/AIDS Prevention, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, Guangdong, China
| | - Bosheng Li
- Institute of Pathogenic Microorganism, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, Guangdong, China
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11
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Koenig AB, Tan A, Abdelaal H, Monge F, Younossi ZM, Goodman ZD. Review article: Hepatic steatosis and its associations with acute and chronic liver diseases. Aliment Pharmacol Ther 2024; 60:167-200. [PMID: 38845486 DOI: 10.1111/apt.18059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 04/23/2024] [Accepted: 05/13/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND Hepatic steatosis is a common finding in liver histopathology and the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), whose global prevalence is rising. AIMS To review the histopathology of hepatic steatosis and its mechanisms of development and to identify common and rare disease associations. METHODS We reviewed literature on the basic science of lipid droplet (LD) biology and clinical research on acute and chronic liver diseases associated with hepatic steatosis using the PubMed database. RESULTS A variety of genetic and environmental factors contribute to the development of chronic hepatic steatosis or steatotic liver disease, which typically appears macrovesicular. Microvesicular steatosis is associated with acute mitochondrial dysfunction and liver failure. Fat metabolic processes in hepatocytes whose dysregulation leads to the development of steatosis include secretion of lipoprotein particles, uptake of remnant lipoprotein particles or free fatty acids from blood, de novo lipogenesis, oxidation of fatty acids, lipolysis and lipophagy. Hepatic insulin resistance is a key feature of MASLD. Seipin is a polyfunctional protein that facilitates LD biogenesis. Assembly of hepatitis C virus takes place on LD surfaces. LDs make important, functional contact with the endoplasmic reticulum and other organelles. CONCLUSIONS Diverse liver pathologies are associated with hepatic steatosis, with MASLD being the most important contributor. The biogenesis and dynamics of LDs in hepatocytes are complex and warrant further investigation. Organellar interfaces permit co-regulation of lipid metabolism to match generation of potentially toxic lipid species with their LD depot storage.
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Affiliation(s)
- Aaron B Koenig
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
| | - Albert Tan
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia, USA
| | - Hala Abdelaal
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia, USA
| | - Fanny Monge
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia, USA
| | - Zobair M Younossi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- The Global NASH Council, Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | - Zachary D Goodman
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia, USA
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12
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Seurre C, Roca Suarez AA, Testoni B, Zoulim F, Grigorov B. After the Storm: Persistent Molecular Alterations Following HCV Cure. Int J Mol Sci 2024; 25:7073. [PMID: 39000179 PMCID: PMC11241208 DOI: 10.3390/ijms25137073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 06/24/2024] [Accepted: 06/26/2024] [Indexed: 07/16/2024] Open
Abstract
The development of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has revolutionized the management of this pathology, as their use allows viral elimination in a large majority of patients. Nonetheless, HCV remains a major public health problem due to the multiple challenges associated with its diagnosis, treatment availability and development of a prophylactic vaccine. Moreover, HCV-cured patients still present an increased risk of developing hepatic complications such as hepatocellular carcinoma. In the present review, we aim to summarize the impact that HCV infection has on a wide variety of peripheral and intrahepatic cell populations, the alterations that remain following DAA treatment and the potential molecular mechanisms implicated in their long-term persistence. Finally, we consider how recent developments in single-cell multiomics could refine our understanding of this disease in each specific intrahepatic cell population and drive the field to explore new directions for the development of chemo-preventive strategies.
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Affiliation(s)
- Coline Seurre
- INSERM U1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, 69434 Lyon, France; (C.S.); (A.A.R.S.); (B.T.); (F.Z.)
- The Lyon Hepatology Institute EVEREST, 69003 Lyon, France
| | - Armando Andres Roca Suarez
- INSERM U1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, 69434 Lyon, France; (C.S.); (A.A.R.S.); (B.T.); (F.Z.)
- The Lyon Hepatology Institute EVEREST, 69003 Lyon, France
| | - Barbara Testoni
- INSERM U1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, 69434 Lyon, France; (C.S.); (A.A.R.S.); (B.T.); (F.Z.)
- The Lyon Hepatology Institute EVEREST, 69003 Lyon, France
| | - Fabien Zoulim
- INSERM U1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, 69434 Lyon, France; (C.S.); (A.A.R.S.); (B.T.); (F.Z.)
- The Lyon Hepatology Institute EVEREST, 69003 Lyon, France
- Hospices Civils de Lyon, 69002 Lyon, France
| | - Boyan Grigorov
- INSERM U1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, 69434 Lyon, France; (C.S.); (A.A.R.S.); (B.T.); (F.Z.)
- The Lyon Hepatology Institute EVEREST, 69003 Lyon, France
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13
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Cespiati A, Coelho Rodrigues I, Santos I, Policarpo S, Carvalhana S, Fracanzani AL, Cortez-Pinto H. Effect of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, and associated metabolic comorbidities: A systematic review. Liver Int 2024; 44:1075-1092. [PMID: 38385567 DOI: 10.1111/liv.15876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 12/11/2023] [Accepted: 02/08/2024] [Indexed: 02/23/2024]
Abstract
BACKGROUND AND AIMS The beneficial effect of Hepatitis C virus (HCV) eradication by direct antiviral agents (DAAs) on liver fibrosis is well defined. Despite this, the impact of viral eradication in both hepatic and extra-hepatic metabolic features is underreached. This systematic review aimed to synthesize the evidence on the impact of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, glucidic impairment, dyslipidaemia, and weight gain. METHODS A systematic search of the existing literature (up to December 2022) identified 97 original studies that fulfilled the inclusion criteria. RESULTS Whereas total cholesterol and low-density lipoprotein (LDL) seem to increase after viral eradication, the cardiovascular damage expressed as carotid plaques and intima-media thickness seems to improve. Otherwise, the effect on liver steatosis, glucidic homeostasis, and weight seems to be strictly dependent on the presence of baseline metabolic disorders. CONCLUSION Despite high heterogeneity and relatively short follow-up of included studies, we can conclude that the presence of metabolic risk factors should be strictly evaluated due to their impact on liver steatosis, glucidic and lipid homeostasis, and on weight gain to better identify patients at risk of liver disease progression despite the virus eradication.
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Affiliation(s)
- Annalisa Cespiati
- Unit of Medicine and Metabolic Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Inês Coelho Rodrigues
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
| | - Inês Santos
- Laboratório de Nutrição, Faculdade de Medicina, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal
- Faculdade de Medicina, Instituto de Saúde Ambiental (ISAMB), Universidade de Lisboa, Lisbon, Portugal
| | - Sara Policarpo
- Laboratório de Nutrição, Faculdade de Medicina, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal
- Serviço de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, E.P.E., Lisbon, Portugal
| | - Sofia Carvalhana
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Anna Ludovica Fracanzani
- Unit of Medicine and Metabolic Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Helena Cortez-Pinto
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
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Abstract
The steatotic diseases of metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and chronic hepatitis C (HCV) account for the majority of liver disease prevalence, morbidity, and mortality worldwide. While these diseases have distinct pathogenic and clinical features, dysregulated lipid droplet (LD) organelle biology represents a convergence of pathogenesis in all three. With increasing understanding of hepatocyte LD biology, we now understand the roles of LD proteins involved in these diseases but also how genetics modulate LD biology to either exacerbate or protect against the phenotypes associated with steatotic liver diseases. Here, we review the history of the LD organelle and its biogenesis and catabolism. We also review how this organelle is critical not only for the steatotic phenotype of liver diseases but also for their advanced phenotypes. Finally, we summarize the latest attempts and challenges of leveraging LD biology for therapeutic gain in steatotic diseases. In conclusion, the study of dysregulated LD biology may lead to novel therapeutics for the prevention of disease progression in the highly prevalent steatotic liver diseases of MASLD, ALD, and HCV.
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Affiliation(s)
- Joseph L Dempsey
- Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington
| | - George N Ioannou
- Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington
- Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System Seattle, Washington
| | - Rotonya M Carr
- Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington
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15
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Nasr P, Jönsson C, Ekstedt M, Kechagias S. Non-metabolic causes of steatotic liver disease. METABOLISM AND TARGET ORGAN DAMAGE 2023; 3. [DOI: 10.20517/mtod.2023.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Hepatic steatosis is caused by exaggerated hepatic lipid accumulation and is a common histological and radiological finding. Non-alcoholic fatty liver disease (NAFLD), or metabolic dysfunction associated steatotic liver disease (MASLD), is highly associated with metabolic syndrome and represents the most common cause of hepatic steatosis. However, since several comorbidities, lifestyle factors, and drugs can cause hepatic steatosis, MASLD is, to some extent, a diagnosis of exclusion. Nevertheless, initiatives have been taken to encompass positive (instead of negative) criteria for diagnosis - such as the presence of cardiometabolic risk factors together with hepatic steatosis. Nonetheless, before confirming a patient with MASLD, it is essential to map and evaluate other causes of fatty liver disease or steatotic liver disease. Several causes of hepatic steatosis have been identified in studies; however, the study cohorts are scarce and often anecdotal. Additionally, many studies have shown correlation without proving causation, and many are retrospective without reporting relevant patient characteristics and comorbidities - making it difficult to draw conclusions regarding the underlying etiology or present comorbidity of hepatic steatosis. In this narrative review, we aimed to identify and summarize present studies evaluating the impact of the most common and often suggested causes of hepatic steatosis.
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16
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Kuroda H, Oguri T, Kamiyama N, Toyoda H, Yasuda S, Imajo K, Suzuki Y, Sugimoto K, Akita T, Tanaka J, Yasui Y, Kurosaki M, Izumi N, Nakajima A, Fujiwara Y, Abe T, Kakisaka K, Matsumoto T, Kumada T. Multivariable Quantitative US Parameters for Assessing Hepatic Steatosis. Radiology 2023; 309:e230341. [PMID: 37787670 DOI: 10.1148/radiol.230341] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/04/2023]
Abstract
Background Because of the global increase in the incidence of nonalcoholic fatty liver disease, the development of noninvasive, widely available, and highly accurate methods for assessing hepatic steatosis is necessary. Purpose To evaluate the performance of models with different combinations of quantitative US parameters for their ability to predict at least 5% steatosis in patients with chronic liver disease (CLD) as defined using MRI proton density fat fraction (PDFF). Materials and Methods Patients with CLD were enrolled in this prospective multicenter study between February 2020 and April 2021. Integrated backscatter coefficient (IBSC), signal-to-noise ratio (SNR), and US-guided attenuation parameter (UGAP) were measured in all participants. Participant MRI PDFF value was used to define at least 5% steatosis. Four models based on different combinations of US parameters were created: model 1 (UGAP alone), model 2 (UGAP with IBSC), model 3 (UGAP with SNR), and model 4 (UGAP with IBSC and SNR). Diagnostic performance of all models was assessed using area under the receiver operating characteristic curve (AUC). The model was internally validated using 1000 bootstrap samples. Results A total of 582 participants were included in this study (median age, 64 years; IQR, 52-72 years; 274 female participants). There were 364 participants in the steatosis group and 218 in the nonsteatosis group. The AUC values for steatosis diagnosis in models 1-4 were 0.92, 0.93, 0.95, and 0.96, respectively. The C-indexes of models adjusted by the bootstrap method were 0.92, 0.93, 0.95, and 0.96, respectively. Compared with other models, models 3 and 4 demonstrated improved discrimination of at least 5% steatosis (P < .01). Conclusion A model built using the quantitative US parameters UGAP, IBSC, and SNR could accurately discriminate at least 5% steatosis in patients with CLD. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Han in this issue.
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Affiliation(s)
- Hidekatsu Kuroda
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Takuma Oguri
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Naohisa Kamiyama
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Hidenori Toyoda
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Satoshi Yasuda
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Kento Imajo
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Yasuaki Suzuki
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Katsutoshi Sugimoto
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Tomoyuki Akita
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Junko Tanaka
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Yutaka Yasui
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Masayuki Kurosaki
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Namiki Izumi
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Atsushi Nakajima
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Yudai Fujiwara
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Tamami Abe
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Keisuke Kakisaka
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Takayuki Matsumoto
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
| | - Takashi Kumada
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan (H.K., Y.F., T. Abe, K.K., T.M.); Ultrasound General Imaging, GE HealthCare, Hino, Japan (T.O., N.K.); Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan (H.T., S.Y.); Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan (K.I.); Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan (Y.S.); Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K.S.); Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan (T. Akita, J.T.); Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan (Y.Y., M.K., N.I.); Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.N.); and Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan (T.K.)
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Tsujita Y, Sofue K, Ueshima E, Ueno Y, Hori M, Murakami T. Clinical Application of Quantitative MR Imaging in Nonalcoholic Fatty Liver Disease. Magn Reson Med Sci 2023; 22:435-445. [PMID: 35584952 PMCID: PMC10552668 DOI: 10.2463/mrms.rev.2021-0152] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 03/23/2022] [Indexed: 11/09/2022] Open
Abstract
Viral hepatitis was previously the most common cause of chronic liver disease. However, in recent years, nonalcoholic fatty liver disease (NAFLD) cases have been increasing, especially in developed countries. NAFLD is histologically characterized by fat, fibrosis, and inflammation in the liver, eventually leading to cirrhosis and hepatocellular carcinoma. Although biopsy is the gold standard for the assessment of the liver parenchyma, quantitative evaluation methods, such as ultrasound, CT, and MRI, have been reported to have good diagnostic performances. The quantification of liver fat, fibrosis, and inflammation is expected to be clinically useful in terms of the prognosis, early intervention, and treatment response for the management of NAFLD. The aim of this review was to discuss the basics and prospects of MRI-based tissue quantifications of the liver, mainly focusing on proton density fat fraction for the quantification of fat deposition, MR elastography for the quantification of fibrosis, and multifrequency MR elastography for the evaluation of inflammation.
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Affiliation(s)
- Yushi Tsujita
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Keitaro Sofue
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Eisuke Ueshima
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Yoshiko Ueno
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Masatoshi Hori
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Takamichi Murakami
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
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Thi Thu PN, Hoang Van D, Ngo Thi Quynh M, Tran Thi N, Pham Minh K, Pham Van L. Metabolic, renal, and hematological changes in chronic hepatitis C patients achieving rapid virologic response after 12 weeks of direct-acting antiviral treatment: A prospective cohort study. PLoS One 2023; 18:e0290235. [PMID: 37656689 PMCID: PMC10473482 DOI: 10.1371/journal.pone.0290235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 08/05/2023] [Indexed: 09/03/2023] Open
Abstract
The impact of direct-acting antivirals (DAA) therapy on lipid and glucose metabolism and kidney function in patients with hepatitis C virus (HCV) infection, along with its side effects on blood cells, remains controversial. Therefore, we conducted a study that enrolled 280 patients with HCV infection who achieved sustained virologic response after treatment with DAA therapy without ribavirin to evaluate the metabolic changes, renal function, and anemia risk based on real-world data. This study was an observational prospective study with a follow-up period of 12 weeks after the initiation of DAA therapy. Data on biochemical tests, renal function, blood counts, viral load, and host genomics were recorded before treatment and after 12 weeks of treatment with DAAs. DAA therapy reduced fibrosis-4 scores and improved liver function, with significant reductions in aspartate transaminase, alanine aminotransferase, and total bilirubin levels. However, DAA therapy slightly increased uric acid, cholesterol, and low-density lipoprotein cholesterol levels. It significantly reduced fasting blood glucose levels and hemoglobin A1C index (HbA1C) in the study group, while hemoglobin (Hb) and hematocrit (HCT) concentrations decreased significantly (4.78 ± 21.79 g/L and 0.09% ± 0.11%, respectively). The estimated glomerular filtration rate (eGFR) decreased by 12.89 ± 39.04 mL/min/1.73m2. Most variations were not related to the genotype, except for Hb, HCT, and HbA1C. Anemia incidence increased from 23.58% before treatment to 30.72% after treatment. Patients with HCV-1 genotype had a higher rate of anemia than did patients with genotype 6 (36.23% vs. 24.62%). Multivariate analysis showed that the risk of anemia was related to female sex, cirrhosis status, fibrosis-4 score, pretreatment eGFR, and pretreatment Hb level. The results of our study can provide helpful information to clinicians for the prognosis and treatment of HCV infection.
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Affiliation(s)
- Phuong Nguyen Thi Thu
- Haiphong International Hospital, Haiphong, Vietnam
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | | | | | - Ngan Tran Thi
- Haiphong International Hospital, Haiphong, Vietnam
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | - Khue Pham Minh
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | - Linh Pham Van
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
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Yang XC, Hong ZP, Wang Y, Meng N, Hu Y, Xiong QY, Qin DW, Shen D, Yang XL. Growth history of hepatitis C virus among HIV/HCV co-infected patients in Guizhou Province. Front Genet 2023; 14:1171892. [PMID: 37347053 PMCID: PMC10280012 DOI: 10.3389/fgene.2023.1171892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 05/04/2023] [Indexed: 06/23/2023] Open
Abstract
Background: The evolutionary and epidemiological history and the regional differences of various hepatitis C virus (HCV) genotypes are complex. Our aim was to better understand the molecular epidemiology and evolutionary dynamics of HCV among HIV/HCV co-infected individuals in Guizhou Province. This information could contribute to improve HCV prevention and control strategies in Guizhou and surrounding provinces. Methods: The HCV RNA was extracted from the serum of HIV/HCV co-infected patients, and reverse transcription/nested PCR was performed to amplify nucleotide sequences of the C-E1 region. Then, the successfully amplified sequences were selected for phylogenetic analysis. The available C-E1 region reference sequences from the surrounding provinces of Guizhou (Guangxi, Yunnan, Hunan, and Sichuan) were retrieved in GenBank, and the evolutionary analysis by Bayesian Markov chain Monte Carlo (MCMC) algorithm was performed using BEAST software to reconstruct a phylogeographic tree in order to explore their migration patterns. Finally, the epidemiological history of HCV in the Guizhou region was retraced by reconstructing Bayesian skyline plots (BSPs) after excluding sequences from surrounding provinces. Results: Among 186 HIV/HCV co-infected patients, the C-E1 region sequence was successfully amplified in 177 cases. Phylogenetic analysis classified these sequences into six subtypes: 1a, 1b, 3a, 3b, 6a, and 6n. Among them, subtype 6a was the most dominant strain (n = 70), followed by 3b (n = 55), 1b (n = 31), 3a (n = 11), 1a (n = 8), and 6n (n = 2). By reconstructing the phylogeographic tree, we estimated that the 6a strain in Guizhou mainly originated from Yunnan and Guangxi, while the 3b strain emerged due to transmission from the IDU network in Yunnan. Subtypes 1b, 3a, 3b, and 6a, as the major subtypes of HCV in HIV/HCV co-infected individuals in Guizhou, emerged and later grew more rapidly than the national average. Notably, BSPs of the currently prevalent HCV predominant strain subtype 6a in Guizhou have shown a rapid population growth since 2004. Although the growth rate slowed down around 2010, this growth has continued to date. Conclusion: Overall, despite the improvement and implementation of a series of HCV prevention and control policies and measures, a delayed growth pattern may indicate a unique history of the spread of 6a in Guizhou. Its trend as the dominant strain in Guizhou in recent years may continue to increase slowly over subsequent years.
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Affiliation(s)
- Xiu-Cheng Yang
- Department of Infectious Disease Control, Aba Center for Disease Control and Prevention, Aba, Sichuan, China
| | - Zhang-Ping Hong
- Department of Laboratory, Guiyang Medical Center for Public Health, Guiyang, Guizhou, China
| | - Yi Wang
- Department of Laboratory, Guiyang Medical Center for Public Health, Guiyang, Guizhou, China
| | - Nan Meng
- Department of Laboratory, Guiyang Medical Center for Public Health, Guiyang, Guizhou, China
| | - Yong Hu
- School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, China
| | - Qian-Yu Xiong
- Department of Laboratory, Guiyang Medical Center for Public Health, Guiyang, Guizhou, China
| | - Da-Wen Qin
- School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, China
| | - Du Shen
- School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, China
| | - Xing-Lin Yang
- Department of Laboratory, Guiyang Medical Center for Public Health, Guiyang, Guizhou, China
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20
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Maunye TK, Gededzha MP, Blackard JT, Rakgole JN, Selabe SG. Hepatitis C Virus Genotype 5 Variability in Treatment-Naïve Patients in South Africa. Intervirology 2023; 66:77-87. [PMID: 37231989 PMCID: PMC10353306 DOI: 10.1159/000528178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 11/14/2022] [Indexed: 05/27/2023] Open
Abstract
INTRODUCTION Hepatitis C virus (HCV) genotype 5 was originally identified in South Africa, where it represents 35-60% of all HCV infections. There are limited data on resistance-associated variants (RAVs) in South Africa. Thus, we investigated variability within the NS3/NS4A, NS5A, and NS5B genes of treatment-naïve individuals with HCV genotype 5 infection at the Dr. George Mukhari Academic Hospital (DGMAH) in Pretoria, South Africa. METHODS Nested PCR was performed to amplify the NS3/4A, NS5A, and NS5B genes. RAVs were evaluated using the Geno2pheno tool. RESULTS In the NS3/4A gene, F56S and T122A were detected in one sample each. The D168E mutation was detected in 7 samples. Within the NS5A gene, the T62M mutation was detected in 2 individuals. In the NS5B gene, 8 of 12 individuals (67%) had the A421V mutation, while all 12 individuals (100%) had the S486A mutation. DISCUSSION RAVs were detected frequently among treatment-naïve individuals with HCV genotype 5 infection in South Africa. Thus, resistance testing may be prudent when initiating treatment of patients with genotype 5 infection. Additional population-based studies are needed to understand the prevalence of these RAVs during HCV genotype 5 infection.
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Affiliation(s)
- Tshegofatso K Maunye
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria, South Africa
- National Health Laboratory Service, Pretoria, South Africa
| | - Maemu P Gededzha
- Department of Immunology, Faculty of Health Sciences, University of Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa
| | - Jason T Blackard
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria, South Africa,
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA,
| | - Johnny N Rakgole
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria, South Africa
| | - Selokela G Selabe
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria, South Africa
- National Health Laboratory Service, Pretoria, South Africa
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21
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Ullah A, Rehman IU, Ommer K, Ahmed N, Odenthal M, Yu X, Ahmad J, Nadeem T, Ali Q, Ahmad B. Circulating miRNA-192 and miR-29a as Disease Progression Biomarkers in Hepatitis C Patients with a Prevalence of HCV Genotype 3. Genes (Basel) 2023; 14:genes14051056. [PMID: 37239415 DOI: 10.3390/genes14051056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 05/02/2023] [Accepted: 05/03/2023] [Indexed: 05/28/2023] Open
Abstract
MicroRNAs miR-29a and miR-192 are involved in inflammatory and fibrotic processes of chronic liver disease, and circulating miR-29a is suggested to diagnose fibrosis progression due to hepatitis C virus (HCV) infection. This study aimed to evaluate the expression profile of circulating miR-192 and 29a in a patient cohort with a high frequency of HCV genotype-3. A total of 222 HCV blood samples were collected and serum were separated. Patients were classified into mild, moderate, and severe liver injury based on their Child-Turcotte-Pugh CTP score. RNA was isolated from the serum and used for quantitative real-time PCR. The HCV genotype-3 (62%) was the predominant HCV genotype. In HCV patients, the serum miR-192 and miR-29a levels were significantly upregulated in comparison to healthy controls (p = 0.0017 and p = 0.0001, respectively). The progression rate of miR-192 and 29a in the patient group with mild was highly upregulated compared to patients with moderate and severe hepatitis infection. The ROC curve of miR-192 and miR-29a of moderate liver disease had a significant diagnostic performance compared to the other HCV-infected groups. The increase in miR-29a and miR-192 serum levels was even slightly higher in patients with HCV genotype-3 than in non-genotype-3 patients. In conclusion, serum miR-192 and miR-29a levels significantly increased during the progression of chronic HCV infection. The marked upregulation in patients with HCV genotype-3 suggests them as potential biomarkers for hepatic disease, independently of the HCV genotype.
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Affiliation(s)
- Amin Ullah
- Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan
- Institute for Pathology, University of Cologne, 50923 Cologne, Germany
| | - Irshad Ur Rehman
- Center of Biotechnology and Microbiology, University of Peshawar, Peshawar 25000, Pakistan
| | - Katharina Ommer
- Institute of Transfusion Medicine, University of Cologne, 50923 Cologne, Germany
| | - Nadeem Ahmed
- Center of Excellence in Molecular Biology, University of the Punjab, Lahore 54000, Pakistan
| | | | - Xiaojie Yu
- Institute for Pathology, University of Cologne, 50923 Cologne, Germany
| | - Jamshaid Ahmad
- Center of Biotechnology and Microbiology, University of Peshawar, Peshawar 25000, Pakistan
| | - Tariq Nadeem
- Center of Excellence in Molecular Biology, University of the Punjab, Lahore 54000, Pakistan
| | - Qurban Ali
- Department of Plant Breeding and Genetics, University of the Punjab, Lahore 54000, Pakistan
| | - Bashir Ahmad
- Center of Biotechnology and Microbiology, University of Peshawar, Peshawar 25000, Pakistan
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22
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Gavril OI, Gavril RS, Mitu F, Gavrilescu O, Popa IV, Tatarciuc D, Drugescu A, Oprescu AC, Gherasim A, Mihalache L, Esanu IM. The Influence of Metabolic Factors in Patients with Chronic Viral Hepatitis C Who Received Oral Antiviral Treatment. Metabolites 2023; 13:metabo13040571. [PMID: 37110229 PMCID: PMC10144226 DOI: 10.3390/metabo13040571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/12/2023] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
Hepatic diseases pose a significant public health concern. Regardless of the severity of hepatic fibrosis, treatment is recommended for all chronic hepatitis C virus (HCV) subjects. However, fibrosis and steatosis assessment remains crucial for evaluating the prognosis, progression, and hepatic disease monitoring, particularly following the treatment with direct-acting antivirals (DAAs). The aim of our study was to evaluate the impact of metabolic factors and the extent of hepatic fibrosis and fat accumulation in chronic HCV infection subjects. Additionally, another objective was to investigate modifications regarding fibrosis and steatosis three months after a successful sustained viral response (SVR). A total of 100 patients with compensated cirrhosis and chronic hepatitis C (CHC) were included in our study. These patients received treatment with DAA and underwent Fibromax assessment before and three months post SVR. After DAA treatment, a significant decrease was observed in the degree of hepatic fibrosis and hepatic steatosis. This regression was evident three months following the achievement of SVR. Chronic viral hepatitis C may trigger risk factors for metabolic syndromes, such as obesity and type 2 diabetes mellitus. Conclusions: It is crucial to monitor metabolic factors and take timely measures to prevent or treat metabolic syndrome in patients with chronic viral hepatitis C.
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Affiliation(s)
- Oana Irina Gavril
- Department of Medical Specialties (I), Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Radu Sebastian Gavril
- Department of Medical Specialties (I), Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Florin Mitu
- Department of Medical Specialties (I), Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
- Academy of Medical Sciences of Romania, Bucuresti 030171, Romania
| | - Otilia Gavrilescu
- Department of Medical Specialties (I), Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Iolanda Valentina Popa
- Department of Medical Specialties (I), Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Diana Tatarciuc
- Department of Medical Specialties (I), Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Andrei Drugescu
- Department of Medical Specialties (I), Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Andrei Catalin Oprescu
- Department of Medical Specialties (II), Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Andreea Gherasim
- Morpho-Functional Department, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Laura Mihalache
- Morpho-Functional Department, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Irina Mihaela Esanu
- Department of Medical Specialties (I), Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania
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23
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Han CL, Tian BW, Yang CC, Yang YF, Ma YL, Ding ZN, Yan LJ, Liu H, Dong ZR, Chen ZQ, Hong JG, Wang DX, Li T. The association of fatty liver and risk of hepatocellular carcinoma in HBV or HCV infected individuals: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol 2023; 17:189-198. [PMID: 36625022 DOI: 10.1080/17474124.2023.2166930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Fatty liver (FL) is reportedly a risk factor for hepatocellular carcinoma (HCC) in individuals affected with Hepatitis C (HCV) or B (HBV) virus. However, the results are contradictory, necessitating a meta-analysis. RESEARCH DESIGN AND METHODS Sixteen relevant studies involving 88,618 individuals were retrieved from the Cochrane Library, PubMed, MEDLINE, Embase, and Scopus databases from their inception to 10 December 2022. The hazard ratios (HR) and 95% confidence intervals (CI) were analyzed. RESULTS Liver biopsy-proven FL may be a significant risk factor for HCC in individuals affected with HBV (univariate analyses: HR = 3.13, 95% CI = 1.69-5.79; multivariate analyses: HR = 3.42, 95% CI = 0.83-14.09) as well as HCV (univariate analyses: HR = 1.64, 95% CI = 0.93-2.90; multivariate analyses: HR = 1.75, 95% CI = 1.02-3.00). However, the presence of FL confirmed using reasonable methods other than liver biopsy may not indicate a risk for HCC in HBV-infected individuals (univariate analyses: HR = 0.90, 95% CI = 0.44-1.81; multivariate analyses: HR = 0.69, 95% CI = 0.45-1.08). CONCLUSIONS Biopsy-proven FL may be a significant risk factor for HCC in HCV/HBV-infected individuals. Thus, such individuals should receive suitable interventions to prevent HCC formation or at least attenuate the risk of HCC.
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Affiliation(s)
- Cheng-Long Han
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Bao-Wen Tian
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Chun-Cheng Yang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Ya-Fei Yang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Yun-Long Ma
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Lun-Jie Yan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhi-Qiang Chen
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Jian-Guo Hong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Tao Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China.,Department of Hepatobiliary Surgery, the Second Hospital of Shandong University, Jinan, P.R. China
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24
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Hepatitis C Virus-Lipid Interplay: Pathogenesis and Clinical Impact. Biomedicines 2023; 11:biomedicines11020271. [PMID: 36830808 PMCID: PMC9953247 DOI: 10.3390/biomedicines11020271] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/13/2023] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
Hepatitis C virus (HCV) infection represents the major cause of chronic liver disease, leading to a wide range of hepatic diseases, including cirrhosis and hepatocellular carcinoma. It is the leading indication for liver transplantation worldwide. In addition, there is a growing body of evidence concerning the role of HCV in extrahepatic manifestations, including immune-related disorders and metabolic abnormalities, such as insulin resistance and steatosis. HCV depends on its host cells to propagate successfully, and every aspect of the HCV life cycle is closely related to human lipid metabolism. The virus circulates as a lipid-rich particle, entering the hepatocyte via lipoprotein cell receptors. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation (steatosis) and circulating hypocholesterolemia. Patients with chronic HCV are at increased risk for hepatic steatosis, dyslipidemia, and cardiovascular disease, including accelerated atherosclerosis. This review aims to describe different aspects of the HCV viral life cycle as it impacts host lipoproteins and lipid metabolism. It then discusses the mechanisms of HCV-related hepatic steatosis, hypocholesterolemia, and accelerated atherosclerosis.
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25
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Roy A, Roy M, Gacem A, Datta S, Zeyaullah M, Muzammil K, Farghaly TA, Abdellattif MH, Yadav KK, Simal-Gandara J. Role of bioactive compounds in the treatment of hepatitis: A review. Front Pharmacol 2022; 13:1051751. [PMID: 36618936 PMCID: PMC9810990 DOI: 10.3389/fphar.2022.1051751] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 11/24/2022] [Indexed: 12/24/2022] Open
Abstract
Hepatitis causes liver infection leading to inflammation that is swelling of the liver. They are of various types and detrimental to human beings. Natural products have recently been used to develop antiviral drugs against severe viral infections like viral hepatitis. They are usually extracted from herbs or plants and animals. The naturally derived compounds have demonstrated significant antiviral effects against the hepatitis virus and they interfere with different stages of the life cycle of the virus, viral release, replication, and its host-specific interactions. Antiviral activities have been demonstrated by natural products such as phenylpropanoids, flavonoids, xanthones, anthraquinones, terpenoids, alkaloids, aromatics, etc., against hepatitis B and hepatitis C viruses. The recent studies conducted to understand the viral hepatitis life cycle, more effective naturally derived drugs are being produced with a promising future for the treatment of the infection. This review emphasizes the current strategies for treating hepatitis, their shortcomings, the properties of natural products and their numerous types, clinical trials, and future prospects as potential drugs.
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Affiliation(s)
- Arpita Roy
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, India,*Correspondence: Arpita Roy, ; Jesus Simal-Gandara,
| | - Madhura Roy
- Centre for Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard University, New Delhi, India
| | - Amel Gacem
- Department of Physics, Faculty of Sciences, University 20 Août 1955, Skikda, Algeria
| | - Shreeja Datta
- Biotechnology Department, Delhi Technological University, Rohini, India
| | - Md. Zeyaullah
- Department of Basic Medical Science, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University, Abha, Saudi Arabia
| | - Khursheed Muzammil
- Department of Public Health, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University, Abha, Saudi Arabia
| | - Thoraya A. Farghaly
- Department of Chemistry, Faculty of Applied Science, Umm Al‐Qura University, Makkah, Saudi Arabia
| | - Magda H. Abdellattif
- Department of Chemistry, College of Science, Taif University, Taif, Saudi Arabia
| | - Krishna Kumar Yadav
- Faculty of Science and Technology, Madhyanchal Professional University, Bhopal, India
| | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Science, Universidade de Vigo, Ourense, Spain,*Correspondence: Arpita Roy, ; Jesus Simal-Gandara,
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26
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Liu P, Li M, Zhao L, Yu H, Zhao C, Chen J, Shi R, Zhou L, Zhou Q, Wu B, Li J. Impact of hepatic steatosis on treatment response of autoimmune hepatitis: A retrospective multicentre analysis. Front Immunol 2022; 13:1040029. [PMID: 36591223 PMCID: PMC9795183 DOI: 10.3389/fimmu.2022.1040029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 11/29/2022] [Indexed: 12/15/2022] Open
Abstract
Background There is a paucity of data on whether steatosis impacts autoimmune hepatitis (AIH) treatment response. We aimed to evaluate the influence of baseline steatosis on the biochemical response, fibrosis progression, and adverse longterm outcomes of AIH. Methods Steatosis was diagnosed by a controlled attenuation parameter (CAP) ≥ 248 dB / m. Only patients who underwent immunosuppressive therapy with available liver histological material at diagnosis and qualified CAP within seven days of the liver biopsy were included. Univariate and multivariate analyses were subsequently conducted. Results The multicentre and retrospective cohort enrolled 222 subjects (88.3% female, median age 54 years, median follow-up 48 months) in the final analysis, and 56 (25.2%) patients had hepatic steatosis. Diabetes, hypertension, and significant fibrosis at baseline were more common in the steatosis group than in the no steatosis group. After adjusting for confounding factors, hepatic steatosis was an independent predictor of insufficient biochemical response (OR: 8.07) and identified as an independent predictor of long-term adverse outcomes (HR: 4.07). By subgroup multivariate analysis (different degrees of steatosis, fibrosis, and prednisone dose), hepatic steatosis independently showed a relatively stable correlation with treatment response. Furthermore, in contrast to those without steatosis, a significant increase in liver stiffness (LS) was observed in patients with steatosis (4.1%/year vs. -16%/year, P < 0.001). Conclusions Concomitant hepatic steatosis was significantly associated with poor response to treatment in AIH patients. Routine CAP measurements are therefore essential to guide the management of AIH.
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Affiliation(s)
- Peiyan Liu
- Clinical School of the Second People’s Hospital, Tianjin Medical University, Tianjin, China,Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, China
| | - Mingkai Li
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China,Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Lili Zhao
- Clinical School of the Second People’s Hospital, Tianjin Medical University, Tianjin, China,Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, China
| | - Hongsheng Yu
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Chang Zhao
- Department of Pathology, The Lingnan Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jianning Chen
- Department of Pathology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ruifang Shi
- Department of Pathology, Tianjin Second People’s Hospital, Tianjin, China
| | - Li Zhou
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, China
| | - Qi Zhou
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China,Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Bin Wu
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China,Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China,*Correspondence: Bin Wu, ; Jia Li,
| | - Jia Li
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, China,*Correspondence: Bin Wu, ; Jia Li,
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27
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Yuri M, Nishimura T, Tada T, Yoshida M, Fujiwara A, Kawata S, Yoshihara K, Yoshioka R, Ota S, Nakano R, Yuri Y, Takashima T, Aizawa N, Ikeda N, Shiomi H, Ide YH, Enomoto H, Yasuhiro F, Yano H, Iijima H. Diagnosis of hepatic steatosis based on ultrasound attenuation imaging is not influenced by liver fibrosis. Hepatol Res 2022; 52:1009-1019. [PMID: 36018852 DOI: 10.1111/hepr.13831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 08/11/2022] [Accepted: 08/18/2022] [Indexed: 12/13/2022]
Abstract
AIM Recently, a new technique using attenuation imaging (ATI) was developed to diagnose hepatic steatosis. The aim of this study was to investigate whether ATI for the evaluation of hepatic steatosis is influenced by liver fibrosis. METHODS A total of 328 patients with chronic liver disease were enrolled to study the associations between histological hepatic steatosis or liver fibrosis and ATI findings. The interaction between liver fibrosis and ATI was also analyzed. RESULTS Median ATI values according to steatosis grade and fibrosis stage increased in line with the progression of liver steatosis (p < 0.001) and fibrosis (p < 0.05). However, in each steatosis grade, ATI values according to fibrosis stage were not significantly increased. In multiple regression analyses for assessment of the effect of their interaction, the p values for fibrosis stage, steatosis grade, and fibrosis stage × steatosis grade were 0.096, <0.001, and 0.077, respectively. Variance inflation factor values for fibrosis stage, steatosis grade, and fibrosis stage × steatosis grade were 1.079, 1.094, and 1.074, respectively. CONCLUSION Attenuation imaging values are not influenced by liver fibrosis.
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Affiliation(s)
- Minako Yuri
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | - Takashi Nishimura
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
- Ultrasound Imaging Center, Hyogo Medical University, Nishinomiya, Japan
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Masahiro Yoshida
- Ultrasound Imaging Center, Hyogo Medical University, Nishinomiya, Japan
| | - Aoi Fujiwara
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | - Shoki Kawata
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | - Kohei Yoshihara
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | - Ryota Yoshioka
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | - Shogo Ota
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | - Ryota Nakano
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | - Yukihisa Yuri
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | - Tomoyuki Takashima
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | - Nobuhiro Aizawa
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | - Naoto Ikeda
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | - Hideyuki Shiomi
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | - Yoshi-Hiro Ide
- Department of Pathology, Hyogo Medical University, Nishinomiya, Japan
| | - Hirayuki Enomoto
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
| | | | - Hirohisa Yano
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Hiroko Iijima
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
- Ultrasound Imaging Center, Hyogo Medical University, Nishinomiya, Japan
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Huang KH, Lee CH, Cheng YD, Gau SY, Tsai TH, Chung NJ, Lee CY. Correlation between long-term use of metformin and incidence of NAFLD among patients with type 2 diabetes mellitus: A real-world cohort study. Front Endocrinol (Lausanne) 2022; 13:1027484. [PMID: 36531446 PMCID: PMC9748475 DOI: 10.3389/fendo.2022.1027484] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 11/09/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND AND AIMS Studies have demonstrated that the short-term use of metformin benefits liver function among patients with type 2 diabetes mellitus (T2DM). However, few studies have reported on the effects of long-term metformin treatment on liver function or liver histology. This study investigated the correlation between metformin use and the incidence of nonalcoholic fatty liver disease (NAFLD) among patients with T2DM. METHODS This population-based study investigated the risk of NAFLD among patients with T2DM who received metformin treatment between 2001-2018. Metformin users and metformin nonusers were enrolled and matched to compare the risk of NAFLD. RESULTS After 3 years, the patients who received <300 cDDD of metformin and those with metformin use intensity of <10 and 10-25 DDD/month had odds ratios (ORs) of 1.11 (95% confidence interval [CI] = 1.06-1.16), 1.08 (95% CI = 1.02-1.13), and 1.18 (95% CI = 1.11-1.26) for NAFLD, respectively. Moreover, metformin users who scored high on the Diabetes Complications and Severity Index (DCSI) were at high risk of NAFLD. Patients with comorbid hyperlipidemia, hyperuricemia, obesity, and hepatitis C were also at high risk of NAFLD. CONCLUSION Patients with T2DM who received metformin of <300 cDDD or used metformin at an intensity of <10 and 10-25 DDD/month were at a high risk of developing NAFLD. The results of this study also indicated that patients with T2DM receiving metformin and with high scores on the DCSI were at a high risk of developing NAFLD.
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Affiliation(s)
- Kuang-Hua Huang
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
| | - Chiu-Hsiang Lee
- School of Nursing, Chung Shan Medical University, Taichung, Taiwan
- Department of Nursing, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yih-Dih Cheng
- School of Pharmacy, China Medical University, Taichung, Taiwan
- Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan
| | - Shuo-Yan Gau
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Tung-Han Tsai
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
| | - Ning-Jen Chung
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Chien-Ying Lee
- Department of Pharmacology, Chung Shan Medical University, Taichung, Taiwan
- Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan
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Imajo K, Toyoda H, Yasuda S, Suzuki Y, Sugimoto K, Kuroda H, Akita T, Tanaka J, Yasui Y, Tamaki N, Kurosaki M, Izumi N, Nakajima A, Kumada T. Utility of Ultrasound-Guided Attenuation Parameter for Grading Steatosis With Reference to MRI-PDFF in a Large Cohort. Clin Gastroenterol Hepatol 2022; 20:2533-2541.e7. [PMID: 34768008 DOI: 10.1016/j.cgh.2021.11.003] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/19/2021] [Accepted: 11/02/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Ultrasound-guided attenuation parameter (UGAP) is recently developed for noninvasive evaluation of steatosis. However, reports on its usefulness in clinical practice are limited. This prospective multicenter study analyzed the diagnostic accuracy of grading steatosis with reference to magnetic resonance imaging-based proton density fat fraction (MRI-PDFF), a noninvasive method with high accuracy, in a large cohort. METHODS Altogether, 1010 patients with chronic liver disease who underwent MRI-PDFF and UGAP were recruited and prospectively enrolled from 6 Japanese liver centers. Linearity was evaluated using intraclass correlation coefficients between MRI-PDFF and UGAP values. Bias, defined as the mean difference between MRI-PDFF and UGAP values, was assessed by Bland-Altman analysis. UGAP cutoffs for pairwise MRI-PDFF-based steatosis grade were determined using area under the receiver-operating characteristic curve (AUROC) analyses. RESULTS UGAP values were shown to be normally distributed. However, because PDFF values were not normally distributed, they were log-transformed (MRI-logPDFF). UGAP values significantly correlated with MRI-logPDFF (intraclass correlation coefficient = 0.768). Additionally, Bland-Altman analysis showed good agreement between MRI-logPDFF and UGAP with a mean bias of 0.0002% and a narrow range of agreement (95% confidence interval [CI], -0.015 to 0.015). The AUROCs for distinguishing steatosis grade ≥1 (MRI-PDFF ≥5.2%), ≥2 (MRI-PDFF ≥11.3%), and 3 (MRI-PDFF ≥17.1%) were 0.910 (95% CI, 0.891-0.928), 0.912 (95% CI, 0.894-0.929), and 0.894 (95% CI, 0.873-0.916), respectively. CONCLUSIONS UGAP has excellent diagnostic accuracy for grading steatosis with reference to MRI-PDFF. Additionally, UGAP has good linearity and negligible bias, suggesting that UGAP has excellent technical performance characteristics that can be widely used in clinical trials and patient care. (UMIN Clinical Trials Registry, Number: UMIN000041196).
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Affiliation(s)
- Kento Imajo
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan.
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yasuaki Suzuki
- Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan
| | - Katsutoshi Sugimoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Hidekatsu Kuroda
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Yahaba, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
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El Ray A, Paradis V, Montasser A, Elghannam M, Shemis M, Nessim I, Abu-Taleb H, Asselah T, Mohamed A, Poté N, Akl M, Marcellin P. Usefulness of the SAF score to characterize NAFLD/NASH in non-cirrhotic HCV patients. EGYPTIAN LIVER JOURNAL 2022. [DOI: 10.1186/s43066-022-00209-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
The SAF score (steatosis, activity, and fibrosis) has been developed for the assessment of the histological severity of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). The aim of this study was to assess the usefulness of the SAF score in a homogenous cohort of Egyptian patients with chronic HCV infection (CHC) without any alcohol consumption and without cirrhosis. We performed a prospective cross-sectional study including 70 consecutive Egyptian patients with chronic HCV infection to assess the usefulness of the SAF score to characterize NAFLD/NASH in non-cirrhotic HCV patients. The inclusion criteria included positive serum anti-HCV IgG antibody and positive HCVRNA, absence of treatment, and absence of cirrhosis (fibrosis score < F4). Patients were divided into two groups: with metabolic syndrome (MS) and without metabolic syndrome (non-MS). All patients were exposed to thorough history taking, full clinical examination, and laboratory and ultrasound assessment. Histopathologic evaluation of the liver biopsy for the assessment of steatosis, activity, grade, and fibrosis stage was assessed by 2 pathologists with experience in liver diseases.
Results
We found that the degree of fibrosis increases with aging. Liver biopsies from CHC patients with metabolic syndrome (MS) exhibited a significantly higher stage of fibrosis than biopsies from those without MS; however, the grade of inflammation did not differ significantly between the two groups. No significant correlation was found between the SAF score and the body mass index (BMI) or serum HCV RNA. No significant relation between SAF score, fibrosis, and MS. No significant relation was found between the MS and the level of HCV viremia.
Conclusion
We concluded that steatosis was associated with the fibrosis stage, independently of MS. This suggests that in this population, steatosis might be more related to HCV infection than to NAFLD and that fibrosis progression might be related, at least in part, to the steatosis process, i.e., virus-associated fatty liver disease (VAFLD).
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31
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Loo JH, Xu WXF, Low JT, Tay WX, Ang LS, Tam YC, Thurairajah PH, Kumar R, Wong YJ. Efficacy and safety of sofosbuvir/velpatasvir with or without ribavirin in hepatitis C genotype 3 compensated cirrhosis: A meta-analysis. World J Hepatol 2022; 14:1248-1257. [PMID: 35978662 PMCID: PMC9258247 DOI: 10.4254/wjh.v14.i6.1248] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 11/18/2021] [Accepted: 05/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) is a leading cause of liver cirrhosis and hepatocellular carcinoma globally. Sofosbuvir/velpatasvir (SOF/VEL) is an effective pan-genotypic direct-acting antiviral combination for treatment of chronic HCV infection. While the addition of ribavirin (RBV) to SOF/VEL improved sustained virological response (SVR12) in genotype 3 (GT3) decompensated cirrhosis patients, the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear. AIM To evaluate the efficacy and safety of SOF/VEL, with or without RBV in GT3 compensated cirrhosis patients. METHODS We searched four electronic databases (PubMed/Medline, Embase, Cochrane Library and Web of Science) from inception up to June 2021 using both free text and MeSH terms. There was no restriction on language, geography, publication dates and publication status (full text or abstracts). All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL, with or without RBV, were included, regardless of age, gender or prior treatment experience. The primary outcome was sustained virological response 12-wk post-treatment (SVR12). The secondary outcome was treatment-related adverse events, as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL. The pooled relative risk (RR), 95%CI and heterogeneity (I 2) were estimated using Review Manager version 5.3. RESULTS From 1752 citations, a total of seven studies (2 randomized controlled trials, 5 cohort studies) with 1088 subjects were identified. The SVR12 was similar in GT3 compensated cirrhosis patients, regardless of the use of RBV, for both the intention-to-treat RR 1.03, 95%CI: 0.99-1.07; I 2 = 0%) and the per-protocol analysis (RR: 1.03, 95%CI: 0.99-1.07; I 2 = 48%). The overall pooled rate of treatment-related adverse events was 7.2%. Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL (RR: 4.20, 95%CI: 1.29-13.68; I 2 = 0%). Subgroup analysis showed that RBV was associated with a higher SVR12 in GT3 compensated cirrhosis patients with baseline resistance-associated substitutions. However, addition of RBV did not significantly increase the SVR12 among treatment-experienced GT3 compensated cirrhosis patients. CONCLUSION Ribavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL. Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients.
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Affiliation(s)
- Jing Hong Loo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Wen Xin Flora Xu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Jun Teck Low
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Wei Xuan Tay
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Le Shaun Ang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Yew Chong Tam
- Education Resource Center, Medical Board, Singapore General Hospital, Singapore 100059, Singapore
| | - Prem Harichander Thurairajah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
- Department of Gastroenterology and Hepatology, National University Hospital, Singapore 119077, Singapore
| | - Rahul Kumar
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
- Duke-NUS Medicine Academic Clinical Program, Singapore 100059, Singapore
| | - Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
- Duke-NUS Medicine Academic Clinical Program, Singapore 100059, Singapore.
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El-Kassas M, Awad A. Metabolic aspects of hepatitis C virus. World J Gastroenterol 2022; 28:2429-2436. [PMID: 35979265 PMCID: PMC9258278 DOI: 10.3748/wjg.v28.i22.2429] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/18/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
Many metabolic factors are associated with chronic hepatitis C virus (HCV) infection and can influence the course of the illness and impact the progression of liver and non-liver-related diseases through complex interactions. Several of these factors impact the course of chronic HCV (CHC) and result in the conceptual translation of CHC from a localized to systemic disease. Besides the traditional liver manifestations associated with CHC infection, such as cirrhosis and hepatocellular carcinoma, various extrahepatic disorders are associated with HCV infection, including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases. The coexistence of metabolic disorders and CHC is known to influence the chronicity and virulence of HCV and accelerates the progression to liver fibrosis and hepatocellular carcinoma. Insulin resistance is one of the key factors that have a tremendous metabolic impact on CHC. Therefore, there is a great need to properly evaluate patients with CHC infection and correct the modifiable metabolic risk factors. Furthermore, patients with HCV who achieved a sustained virological response showed an overall improvement in glucose metabolism, but the exact evidence still requires further studies with long-term follow-up. This review delineates the most recent evidence on the main metabolic factors associated with CHC and the possible influence of chronic HCV infection on metabolic features.
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Affiliation(s)
- Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
| | - Abeer Awad
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
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Mushtaq S, Hashmi AH, Khan A, Asad Raza Kazmi SM, Manzoor S. Emergence and Persistence of Resistance-Associated Substitutions in HCV GT3 Patients Failing Direct-Acting Antivirals. Front Pharmacol 2022; 13:894460. [PMID: 35571102 PMCID: PMC9091354 DOI: 10.3389/fphar.2022.894460] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 03/28/2022] [Indexed: 11/16/2022] Open
Abstract
Background: The hepatitis C virus has a high mutation rate, which results in the emergence of resistance-associated substitutions (RASs). Despite direct-acting antivirals (DAAs) efforts to treat chronically infected HCV genotype 3 (GT3) patients, there are concerns about the emergence and persistence of RASs in DAA failures. The objective of this study was to determine the prevalence of clinically relevant RASs in HCV NS5A and NS5B regions before and after treatment to better understand the role of RASs in treatment failures. Methods: Viral RNA was extracted before and after treatment from serum samples. NS5A and NS5B regions of HCV were amplified by nested PCR, followed by Sanger sequencing. The nucleotide sequences were aligned against HCV GT3 reference sequences, and amino acid substitutions were analyzed using the geno2pheno [hcv] webserver. Results: A total of 76 patients failing DAA therapy were stratified from the cohort of 1388. RASs were detected at the baseline in 15/76 patients and at relapse in 20/76 patients with cirrhosis and previously treated with interferons. The most prevalent NS5A RAS was Y93H found in all treatment-failing patients (14/54 in DCV vs. 6/22 in VEL), followed by A62S/T and A30K. No RASs were identified in NS5B. RASs that were present at the baseline persisted through the 24-week follow-up period and were enriched with emerging RASs during the treatment. The presence of RASs may be one of the causes of treatment failures in 26.3% of patients. Amino acid substitutions were present at the baseline in most of the patients with RASs against NS5A inhibitors. Patients with the baseline Y93H and/or A30K relapse more frequently than patients harboring A62S/T. Conclusion: Treatment-failing patients harbored NS5A RASs, and the most frequent were A30K (5/20), A62S/T (20/20), and Y93H (20/20). Direct resistance testing is recommended for optimizing re-treatment strategies in treatment-failing patients.
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Affiliation(s)
- Saima Mushtaq
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
| | | | - Amjad Khan
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | | | - Sobia Manzoor
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
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Trifan A, Stratina E, Rotaru A, Stafie R, Zenovia S, Nastasa R, Huiban L, Sfarti C, Cojocariu C, Cuciureanu T, Muzica C, Chiriac S, Girleanu I, Singeap AM, Stanciu C. Changes in Liver Steatosis Using Controlled Attenuation Parameter among Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals Therapy Who Achieved Sustained Virological Response. Diagnostics (Basel) 2022; 12:702. [PMID: 35328255 PMCID: PMC8947513 DOI: 10.3390/diagnostics12030702] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection induces hepatic steatosis due to viral and host factors. However, information regarding the effects of direct-acting antivirals (DAAs) therapy on liver steatosis and fibrosis is limited. Vibration-controlled transient elastography (VCTE) with a controlled attenuation parameter (CAP) represents a non-invasive method, which has been used in the last few years for the detection of hepatic steatosis and fibrosis before and at a sustained virological response at 12 weeks (SVR12). The aim of this study was to assess the modifications of liver steatosis and fibrosis in HCV-infected patients who achieved SVR12. Consecutive patients with chronic HCV infection that were treated with DAAs in a tertiary gastroenterology center from Romania were included. Demographics, laboratory data, and VCTE evaluation were recorded in all patients. Patients with previous hepatic decompensation and those who did not achieve SVR were excluded. Two hundred and eighty patients (67.1% females) who achieved SVR12 were included. Regarding the changes in biological parameters, including liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), reduced to normal levels at SVR12 compared to the baseline (28.72 ± 24.71 U/L vs. 40.72 ± 27.34 U/L for ALT, p < 0.013 and 27.21 ± 11.15 U/L vs. 33.35 ± 23.37 U/L for AST, p = 0.029). On the contrary, the levels of triglycerides increased significantly from the baseline to SVR12 (124.03 ± 113.49 mg/dL to 153.78 ± 94.53, p = 0.004). Regarding hepatic steatosis by CAP evaluation, at SVR12, 186 (66.4%) of the individuals had a CAP score of ≥248 dB/m, an increase of 4.6% from the baseline. After viral eradication with DAAs, we observed an increase in hepatic steatosis. Hence, a long-term follow-up is mandatory to identify HCV-infected patients with hepatic steatosis post-SVR and the risk factors for more severe outcomes.
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Affiliation(s)
- Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Ermina Stratina
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Adrian Rotaru
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Remus Stafie
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Robert Nastasa
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Cristina Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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Xu HQ, Wang CG, Zhou Q, Gao YH. Effects of alcohol consumption on viral hepatitis B and C. World J Clin Cases 2021; 9:10052-10063. [PMID: 34904075 PMCID: PMC8638036 DOI: 10.12998/wjcc.v9.i33.10052] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/15/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
The liver is the main target organ for hepatitis viruses and the vital organ for alcohol metabolism. These two factors of viral hepatitis and alcohol abuse in combination can exert dual harmful actions, leading to enhanced damage to the liver. Epidemiological studies have revealed a higher prevalence of hepatitis C virus (HCV) infection among alcoholics than the general population. The interaction of alcohol with viral hepatitis [e.g., hepatitis B virus (HBV), HCV] and the underlying mechanisms are not fully understood. The effects of alcohol on viral hepatitis include promoted viral replication, weakened immune response, and increased oxidative stress. Clinically, alcohol abuse is correlated with an increased risk of developing end-stage liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B and C, suggesting that the combination of alcohol and HBV/HCV lead to more severe liver damage. The influence of mild to moderate alcohol drinking on the HBV-induced liver fibrosis, cirrhosis, and hepatocellular carcinoma among patients infected with HBV remains unclear. Unlike HBV infected patients, no safe level of alcohol intake has been established for patients with HCV. Even light to moderate alcohol use can exert a synergistic effect with viral hepatitis, leading to the rapid progression of liver disease. Furthermore, interferon-based therapy is less effective in alcohol drinkers than in control patients, even after abstinence from alcohol for a period of time. Therefore, abstaining from alcohol is highly recommended to protect the liver, especially in individuals with HBV/HCV infection, to improve the clinical efficacy of antiviral treatment and prevent the rapid progression of chronic viral hepatitis.
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Affiliation(s)
- Hong-Qin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Chun-Guang Wang
- Department of Surgery, The Second Hospital of Jilin University, Jilin University, Changchun 130041, Jilin Province, China
| | - Qiang Zhou
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Yan-Hang Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
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Starekova J, Hernando D, Pickhardt PJ, Reeder SB. Quantification of Liver Fat Content with CT and MRI: State of the Art. Radiology 2021; 301:250-262. [PMID: 34546125 PMCID: PMC8574059 DOI: 10.1148/radiol.2021204288] [Citation(s) in RCA: 132] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 04/19/2021] [Accepted: 04/26/2021] [Indexed: 12/13/2022]
Abstract
Hepatic steatosis is defined as pathologically elevated liver fat content and has many underlying causes. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an increasing prevalence among adults and children. Abnormal liver fat accumulation has serious consequences, including cirrhosis, liver failure, and hepatocellular carcinoma. In addition, hepatic steatosis is increasingly recognized as an independent risk factor for the metabolic syndrome, type 2 diabetes, and, most important, cardiovascular mortality. During the past 2 decades, noninvasive imaging-based methods for the evaluation of hepatic steatosis have been developed and disseminated. Chemical shift-encoded MRI is now established as the most accurate and precise method for liver fat quantification. CT is important for the detection and quantification of incidental steatosis and may play an increasingly prominent role in risk stratification, particularly with the emergence of CT-based screening and artificial intelligence. Quantitative imaging methods are increasingly used for diagnostic work-up and management of steatosis, including treatment monitoring. The purpose of this state-of-the-art review is to provide an overview of recent progress and current state of the art for liver fat quantification using CT and MRI, as well as important practical considerations related to clinical implementation.
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Affiliation(s)
- Jitka Starekova
- From the Departments of Radiology (J.S., D.H., P.J.P., S.B.R.),
Medical Physics (D.H., S.B.R.), Biomedical Engineering (S.B.R.), Medicine
(S.B.R.), and Emergency Medicine (S.B.R.), University of Wisconsin, 1111
Highland Ave, Madison, WI 53705
| | - Diego Hernando
- From the Departments of Radiology (J.S., D.H., P.J.P., S.B.R.),
Medical Physics (D.H., S.B.R.), Biomedical Engineering (S.B.R.), Medicine
(S.B.R.), and Emergency Medicine (S.B.R.), University of Wisconsin, 1111
Highland Ave, Madison, WI 53705
| | - Perry J. Pickhardt
- From the Departments of Radiology (J.S., D.H., P.J.P., S.B.R.),
Medical Physics (D.H., S.B.R.), Biomedical Engineering (S.B.R.), Medicine
(S.B.R.), and Emergency Medicine (S.B.R.), University of Wisconsin, 1111
Highland Ave, Madison, WI 53705
| | - Scott B. Reeder
- From the Departments of Radiology (J.S., D.H., P.J.P., S.B.R.),
Medical Physics (D.H., S.B.R.), Biomedical Engineering (S.B.R.), Medicine
(S.B.R.), and Emergency Medicine (S.B.R.), University of Wisconsin, 1111
Highland Ave, Madison, WI 53705
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Siphepho PY, Liu YT, Shabangu CS, Huang JF, Huang CF, Yeh ML, Yu ML, Wang SC. The Impact of Steatosis on Chronic Hepatitis C Progression and Response to Antiviral Treatments. Biomedicines 2021; 9:1491. [PMID: 34680608 PMCID: PMC8533513 DOI: 10.3390/biomedicines9101491] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/12/2021] [Accepted: 10/13/2021] [Indexed: 02/07/2023] Open
Abstract
Metabolic derangement is characteristic in patients with hepatitis C virus (HCV) infection. Aside from established liver injury, various extrahepatic metabolic disorders impact the natural history of the disease, clinical outcomes, and the efficacy of antiviral therapy. The presence of steatosis, recently redefined as metabolic-associated fatty liver disease (MAFLD), is a common feature in HCV-infected patients, induced by host and/or viral factors. Most chronic HCV-infected (CHC) patients have mild steatosis within the periportal region of the liver with an estimated prevalence of 40% to 86%. Indeed, this is higher than the 19% to 50% prevalence observed in patients with other chronic liver diseases such as chronic hepatitis B (CHB). The histological manifestations of HCV infection are frequently observed in genotype 3 (G-3), where relative to other genotypes, the prevalence and severity of steatosis is also increased. Steatosis may independently influence the treatment efficacy of either interferon-based or interferon-free antiviral regimens. This review aimed to provide updated evidence of the prevalence and risk factors behind HCV-associated steatosis, as well as explore the impact of steatosis on HCV-related outcomes.
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Affiliation(s)
- Phumelele Yvonne Siphepho
- Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (P.Y.S.); (M.-L.Y.)
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
| | - Yi-Ting Liu
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | - Ciniso Sylvester Shabangu
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Jee-Fu Huang
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lung Yu
- Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (P.Y.S.); (M.-L.Y.)
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Shu-Chi Wang
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
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Cespiati A, Petta S, Lombardi R, Di Marco V, Calvaruso V, Bertelli C, Pisano G, Fatta E, Sigon G, Iuculano F, Crapanzano L, Gibilaro G, Francione P, Craxì A, Fargion S, Fracanzani AL. Metabolic comorbidities and male sex influence steatosis in chronic hepatitis C after viral eradication by direct-acting antiviral therapy (DAAs): Evaluation by the controlled attenuation parameter (CAP). Dig Liver Dis 2021; 53:1301-1307. [PMID: 33214063 DOI: 10.1016/j.dld.2020.11.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 10/30/2020] [Accepted: 11/02/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Chronic hepatitis C (CHC) is associated with hepatic steatosis, related to both a direct viral action and metabolic features. Vice-versa data on hepatic steatosis after viral eradication by direct-acting antiviral agents (DAA) are undefined although the presence of metabolic alterations could strongly influence the occurrence of steatosis as in NAFLD. The controlled attenuation parameter (CAP) (FibroscanⓇ) allows the qualitative and quantitative evaluation of fatty liver. AIM to evaluate in patients with CHC whether hepatic steatosis diagnosed by CAP modifies after DAAs-induced sustained virologic response (SVR). METHODS Data were collected the day of DAAs therapy starting and six months after SVR. CAP ≥ 248 dB/m defined the presence of steatosis. RESULTS 794 CHC SVR patients referring to 2 Italian Units were enrolled. Mean age was 64 ± 16 ys, 50% males, BMI 25.4 ± 4 kg/m2, genotype type-1 in 73%, type-3 in 8%. Prevalence of hepatic steatosis at baseline was 32% by US and 46% by CAP. De novo steatosis developed in 125 (29%), resolution in 122 (30%). At multivariate analysis de novo steatosis was independently associated with male sex (OR 1.7, CI 95% 1.09-2.67; p = 0.02) and baseline BMI (for unit increase OR 1.19, CI 95%1.11-1.29; p < 0.001). Baseline BMI (for unit increase OR 0.47, CI 95% 0.25-0.89; p = 0.02) and triglycerides (for unit increase OR 0.93, CI 95% 0.87-0.99; p = 0.03) prevented steatosis resolution after therapy. CONCLUSIONS after SVR de novo steatosis and resolution of baseline steatosis are closely related to the presence of metabolic comorbidities.
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Affiliation(s)
- Annalisa Cespiati
- Unit of Internal Medicine and Metabolic Disease, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Italy; Department of Pathophysiology and Transplantation, University of Milan, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Italy
| | - Rosa Lombardi
- Unit of Internal Medicine and Metabolic Disease, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Italy; Department of Pathophysiology and Transplantation, University of Milan, Italy.
| | - Vito Di Marco
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Italy
| | - Vincenza Calvaruso
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Italy
| | - Cristina Bertelli
- Unit of Internal Medicine and Metabolic Disease, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Italy
| | - Giuseppina Pisano
- Unit of Internal Medicine and Metabolic Disease, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Italy
| | - Erika Fatta
- Unit of Internal Medicine and Metabolic Disease, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Italy
| | - Giordano Sigon
- Unit of Internal Medicine and Metabolic Disease, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Italy; Department of Pathophysiology and Transplantation, University of Milan, Italy
| | - Federica Iuculano
- Unit of Internal Medicine and Metabolic Disease, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Italy; Department of Pathophysiology and Transplantation, University of Milan, Italy
| | - Luciano Crapanzano
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Italy
| | - Gerlando Gibilaro
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Italy
| | - Paolo Francione
- Unit of Internal Medicine and Metabolic Disease, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Italy; Department of Pathophysiology and Transplantation, University of Milan, Italy
| | - Antonio Craxì
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Italy
| | - Silvia Fargion
- Department of Pathophysiology and Transplantation, University of Milan, Italy
| | - Anna Ludovica Fracanzani
- Unit of Internal Medicine and Metabolic Disease, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Italy; Department of Pathophysiology and Transplantation, University of Milan, Italy
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Jia HD, Liang L, Li C, Wu H, Wang H, Liang YJ, Zhou YH, Gu WM, Fan XP, Zhang WG, Chen TH, Chen ZY, Zhong JH, Lau WY, Pawlik TM, Diao YK, Xu QR, Shen F, Zhang CW, Huang DS, Yang T. Long-Term Surgical Outcomes of Liver Resection for Hepatocellular Carcinoma in Patients With HBV and HCV Co-Infection: A Multicenter Observational Study. Front Oncol 2021; 11:700228. [PMID: 34395268 PMCID: PMC8358778 DOI: 10.3389/fonc.2021.700228] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 07/15/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most serious consequences of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study sought to investigate long-term outcomes after liver resection for HCC among patients with HBV/HCV co-infection (HBV/HCV-HCC) compared with patients with HBV infection (HBV-HCC). METHODS Patients who underwent curative-intent liver resection for HCC were identified from a multicenter Chinese database. Using propensity score matching (PSM), patients with HBV/HCV-HCC were matched one-to-one to patients with HBV-HCC. Overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups before and after PSM. RESULTS Among 2,467 patients identified, 93 (3.8%) and 2,374 (96.2%) patients had HBV/HCV-HCC and HBV-HCC, respectively. Compared with patients with HBV-HCC, patients with HBV/HCV-HCC were older, have poorer liver-related characteristics but better tumor-related characteristics. PSM created 88 pairs of patients with comparable liver- and tumor-related characteristics (all P > 0.2). In the PSM cohort, the 3- and 5-year RFS rates in patients with HBV/HCV-HCC were 48.3% and 38.9%, which were significantly poorer than patients with HBV-HCC (61.8% and 49.2%, P = 0.037). Meanwhile, the 3- and 5-year OS rates in patients with HBV/HCV-HCC were also poorer than patients with HBV-HCC (65.4% and 51.1% vs. 73.7% and 63.0%), with a difference close to be significant between them (P = 0.081). CONCLUSION Comparing to patients with HBV-HCC, liver resection resulted in relatively poorer long-term surgical outcomes in patients with HBV/HCV-HCC.
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Affiliation(s)
- Hang-Dong Jia
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou, China
- School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China
| | - Lei Liang
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou, China
- School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Han Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Hong Wang
- Department of General Surgery, Liuyang People’s Hospital, Hunan, China
| | - Ying-Jian Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Harbin Medical University, Heilongjiang, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu’er People’s Hospital, Yunnan, China
| | - Wei-Min Gu
- The First Department of General Surgery, The Fourth Hospital of Harbin, Heilongjiang, China
| | - Xin-Ping Fan
- Department of General Surgery, Pingxiang Mining Group General Hospital, Jiangxi, China
| | - Wan-Guang Zhang
- Department of Hepatic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People’s Hospital, Sichuan, China
| | - Zhi-Yu Chen
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Timothy M. Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, United States
| | - Yong-Kang Diao
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou, China
- School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China
| | - Qiu-Ran Xu
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou, China
- School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Cheng-Wu Zhang
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou, China
| | - Dong-Sheng Huang
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou, China
- School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China
| | - Tian Yang
- Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou, China
- School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
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Saldarriaga OA, Dye B, Pham J, Wanninger TG, Millian D, Kueht M, Freiberg B, Utay N, Stevenson HL. Comparison of liver biopsies before and after direct-acting antiviral therapy for hepatitis C and correlation with clinical outcome. Sci Rep 2021; 11:14506. [PMID: 34267267 PMCID: PMC8282660 DOI: 10.1038/s41598-021-93881-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 06/18/2021] [Indexed: 02/07/2023] Open
Abstract
Direct-acting antivirals (DAA) have replaced interferon (IFN)-based therapies for hepatitis C virus. In this retrospective clinical study, we examined differences in histopathologic features in paired liver biopsies collected from the same patient before and after DAA and correlated these findings with clinical outcome. Biopsies (n = 19) were evaluated by quantitative imaging analysis to measure steatosis and fibrosis. Most patients had decreased steatosis in their post-treatment, follow-up biopsies. However, one patient had a striking increase in steatosis (from 0.86 to 6.32%) and later developed decompensated cirrhosis and hepatocellular carcinoma (HCC). This patient had a marked increase in fibrosis between biopsies, with a CPA of 6.74 to 32.02. Another patient, who already had bridging fibrosis at the time of her pre-treatment biopsy, developed cholangiocarcinoma after DAA. Even though the overall inflammatory activity in the post-treatment biopsies significantly decreased after treatment, 60% of patients had persistent portal lymphocytic inflammation. In summary, DAAs decreased steatosis and hepatic inflammation in most patients, although some may have persistence of lymphocytic portal inflammation. Patients known to have advanced fibrosis at treatment initiation and who have other risk factors for ongoing liver injury, such as steatosis, should be followed closely for the development of adverse outcomes, such as portal hypertension and primary liver cancers.
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Affiliation(s)
- Omar A Saldarriaga
- Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA
| | - Bradley Dye
- School of Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA
| | - Judy Pham
- School of Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA
| | - Timothy G Wanninger
- School of Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA
| | - Daniel Millian
- School of Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA
| | - Michael Kueht
- Dept. of Surgery, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA
| | - Benjamin Freiberg
- Digital Pathology, Araceli Biosciences, 7425 NE Evergreen Pkwy, Hillsboro, OR, 97124, USA
| | - Netanya Utay
- Department of Internal Medicine, University of Texas Health Science Center at Houston, 7000 Fannin St # 1200, Houston, TX, 77030, USA
| | - Heather L Stevenson
- Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA.
- Department of Pathology, The University of Texas Medical Branch, 712 Texas Avenue, Clinical Services Wing-Room 5.506Q, Galveston, TX, 77555-0416, USA.
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Boeckmans J, Rombaut M, Demuyser T, Declerck B, Piérard D, Rogiers V, De Kock J, Waumans L, Magerman K, Cartuyvels R, Rummens JL, Rodrigues RM, Vanhaecke T. Infections at the nexus of metabolic-associated fatty liver disease. Arch Toxicol 2021; 95:2235-2253. [PMID: 34027561 PMCID: PMC8141380 DOI: 10.1007/s00204-021-03069-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 04/29/2021] [Indexed: 02/07/2023]
Abstract
Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease that affects about a quarter of the world population. MAFLD encompasses different disease stadia ranging from isolated liver steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. Although MAFLD is considered as the hepatic manifestation of the metabolic syndrome, multiple concomitant disease-potentiating factors can accelerate disease progression. Among these risk factors are diet, lifestyle, genetic traits, intake of steatogenic drugs, male gender and particular infections. Although infections often outweigh the development of fatty liver disease, pre-existing MAFLD could be triggered to progress towards more severe disease stadia. These combined disease cases might be underreported because of the high prevalence of both MAFLD and infectious diseases that can promote or exacerbate fatty liver disease development. In this review, we portray the molecular and cellular mechanisms by which the most relevant viral, bacterial and parasitic infections influence the progression of fatty liver disease and steatohepatitis. We focus in particular on how infectious diseases, including coronavirus disease-19, hepatitis C, acquired immunodeficiency syndrome, peptic ulcer and periodontitis, exacerbate MAFLD. We specifically underscore the synergistic effects of these infections with other MAFLD-promoting factors.
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Affiliation(s)
- Joost Boeckmans
- Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
- Clinical Laboratory, Jessa Hospital, Stadsomvaart 11, 3500, Hasselt, Belgium.
| | - Matthias Rombaut
- Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Thomas Demuyser
- Department of Microbiology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
- Center for Neurosciences, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Baptist Declerck
- Department of Microbiology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
| | - Denis Piérard
- Department of Microbiology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
| | - Vera Rogiers
- Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Joery De Kock
- Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Luc Waumans
- Clinical Laboratory, Jessa Hospital, Stadsomvaart 11, 3500, Hasselt, Belgium
| | - Koen Magerman
- Clinical Laboratory, Jessa Hospital, Stadsomvaart 11, 3500, Hasselt, Belgium
- Department of Immunology and Infection, Hasselt University, Martelarenlaan 42, 3500, Hasselt, Belgium
| | - Reinoud Cartuyvels
- Clinical Laboratory, Jessa Hospital, Stadsomvaart 11, 3500, Hasselt, Belgium
| | - Jean-Luc Rummens
- Clinical Laboratory, Jessa Hospital, Stadsomvaart 11, 3500, Hasselt, Belgium
| | - Robim M Rodrigues
- Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
| | - Tamara Vanhaecke
- Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
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Lee MK, Chung WJ. Relationship between symptoms and both stage of change in adopting a healthy life style and quality of life in patients with liver cirrhosis: a cross-sectional study. Health Qual Life Outcomes 2021; 19:148. [PMID: 34001156 PMCID: PMC8130318 DOI: 10.1186/s12955-021-01787-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Accepted: 05/04/2021] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Previous studies of patients with liver cirrhosis have not considered the broad range of symptoms or the association between healthy behavior and quality of life. The purposes of this study were to examine the association between symptoms and adopting exercise and consuming fruits and vegetables and to identify factors associated with quality of life in patients with liver cirrhosis. METHODS This cross-sectional study enrolled 91 consecutive patients with liver cirrhosis in one tertiary general hospital in South Korea between February 2016 and January 2017. Each study participant completed a self-administered questionnaire that measured symptom, stage of change in engaging in exercise and consumption of fruits and vegetables, and the Korean version of the 36-item Short-Form Health Survey. Multivariate ordinal logistic regression analysis and multiple regression models was used, respectively, to examine the association between each symptom with stage of change in engaging in exercise and consumption of fruits and vegetables and to evaluate factors affecting quality of life. RESULTS Experiencing nausea was associated with more readiness for change in engaging in exercise, but experiencing shortness of breath was associated with less readiness for change in engaging in exercise. Experiencing right upper quadrant pain was associated with more readiness for change in engaging in consumption of fruits and vegetables. Muscle cramps, anorexia, right upper quadrant pain and body pain, itching, ascites or edema, bruising, and change in appearance negatively affected quality of life. CONCLUSIONS The results suggest that the types of symptoms experienced by a patient with liver cirrhosis hinder or promote the patient's adoption of exercise and dietary behavior. Experiencing symptoms may negatively affect quality of life. Caregivers should provide supportive care to patients with liver cirrhosis, which includes assessing and managing symptoms to improve quality of life.
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Affiliation(s)
- Myung Kyung Lee
- College of Nursing, Research Institute of Nursing Science, Kyungpook National University, 41944, 680 Gukchabosangro, Jung-gu, Daegu, South Korea.
| | - Woo Jin Chung
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
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Pasanta D, Htun KT, Pan J, Tungjai M, Kaewjaeng S, Kim H, Kaewkhao J, Kothan S. Magnetic Resonance Spectroscopy of Hepatic Fat from Fundamental to Clinical Applications. Diagnostics (Basel) 2021; 11:842. [PMID: 34067193 PMCID: PMC8151733 DOI: 10.3390/diagnostics11050842] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 04/29/2021] [Accepted: 05/06/2021] [Indexed: 02/06/2023] Open
Abstract
The number of individuals suffering from fatty liver is increasing worldwide, leading to interest in the noninvasive study of liver fat. Magnetic resonance spectroscopy (MRS) is a powerful tool that allows direct quantification of metabolites in tissue or areas of interest. MRS has been applied in both research and clinical studies to assess liver fat noninvasively in vivo. MRS has also demonstrated excellent performance in liver fat assessment with high sensitivity and specificity compared to biopsy and other imaging modalities. Because of these qualities, MRS has been generally accepted as the reference standard for the noninvasive measurement of liver steatosis. MRS is an evolving technique with high potential as a diagnostic tool in the clinical setting. This review aims to provide a brief overview of the MRS principle for liver fat assessment and its application, and to summarize the current state of MRS study in comparison to other techniques.
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Affiliation(s)
- Duanghathai Pasanta
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (D.P.); (K.T.H.); (J.P.); (M.T.); (S.K.)
| | - Khin Thandar Htun
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (D.P.); (K.T.H.); (J.P.); (M.T.); (S.K.)
| | - Jie Pan
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (D.P.); (K.T.H.); (J.P.); (M.T.); (S.K.)
- Shandong Provincial Key Laboratory of Animal Resistant Biology, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Montree Tungjai
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (D.P.); (K.T.H.); (J.P.); (M.T.); (S.K.)
| | - Siriprapa Kaewjaeng
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (D.P.); (K.T.H.); (J.P.); (M.T.); (S.K.)
| | - Hongjoo Kim
- Department of Physics, Kyungpook National University, Daegu 41566, Korea;
| | - Jakrapong Kaewkhao
- Center of Excellence in Glass Technology and Materials Science (CEGM), Nakhon Pathom Rajabhat University, Nakhon Pathom 73000, Thailand;
| | - Suchart Kothan
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (D.P.); (K.T.H.); (J.P.); (M.T.); (S.K.)
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Chaudhari R, Fouda S, Sainu A, Pappachan JM. Metabolic complications of hepatitis C virus infection. World J Gastroenterol 2021; 27:1267-1282. [PMID: 33833481 PMCID: PMC8015302 DOI: 10.3748/wjg.v27.i13.1267] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 02/10/2021] [Accepted: 03/12/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.
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Affiliation(s)
- Rahul Chaudhari
- Department of Medicine, Pennsylvania Hospital of the University of Pennsylvania, Pennsylvania, PA 19104, United States
| | - Sherouk Fouda
- School of Health and Biomedical Sciences, RMIT University, Melbourne VIC 3000, Australia
| | - Ashik Sainu
- Department of Gastroenterology and Hepatology, Aster Oman Hospital, Al Ghubra, Muscat OM 133, Oman
| | - Joseph M Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, United Kingdom
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Zarębska-Michaluk D. Genotype 3-hepatitis C virus’ last line of defense. World J Gastroenterol 2021; 27:1006-1021. [PMID: 33776369 PMCID: PMC7985731 DOI: 10.3748/wjg.v27.i11.1006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 01/24/2021] [Accepted: 03/01/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic infection with hepatitis C virus (HCV) is one of the leading causes of liver disease globally, affecting approximately 71 million people. The majority of them are infected with genotype (GT) 1 but infections with GT3 are second in frequency. For many years, GT3 was considered to be less pathogenic compared to other GTs in the HCV family due to its favorable response to interferon (IFN)-based regimen. However, the growing evidence of a higher rate of steatosis, more rapid progression of liver fibrosis, and lower efficacy of antiviral treatment compared to infection with other HCV GTs has changed this conviction. This review presents the specifics of the course of GT3 infection and the development of therapeutic options for GT3-infected patients in the era of direct-acting antivirals (DAA). The way from a standard of care therapy with pegylated IFN-alpha (pegIFNα) and ribavirin (RBV) through a triple combination of pegIFNα + RBV and DAA to the highly potent IFN-free pangenotypic DAA regimens is discussed along with some treatment options which appeared to be dead ends. Although the implementation of highly effective pangenotypic regimens is the most recent stage of revolution in the treatment of GT3 infection, there is still room for improvement, especially in patients with liver cirrhosis and those who fail to respond to DAA therapies, particularly those containing inhibitors of HCV nonstructural protein 5A.
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Affiliation(s)
- Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Jan Kochanowski University, Kielce 25-369, Świętokrzyskie, Poland
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Dar GA, Yattoo GN, Gulzar GM, Sodhi JS, Gorka S, Laway MA. Treatment of Chronic Hepatitis C Genotype 3 With Ledipasvir and Sofosbuvir: An Observational Study. J Clin Exp Hepatol 2021; 11:227-231. [PMID: 33746448 PMCID: PMC7953013 DOI: 10.1016/j.jceh.2020.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 06/14/2020] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE Sofosbuvir/ledipasvir (SOF/LED) is recommended for treatment of genotypes 1, 4, 5 and 6. Despite some preliminary data from the ELECTRON-2 trial regarding use of SOF/LED combination in chronic hepatitis C genotype 3, there are no guidelines recommending this combination in such patients. We conducted this study to evaluate the efficacy of the overall sustained virologic response at 12 weeks (SVR 12) and safety of SOF/LED in chronic hepatitis C genotype 3 infection in our population. METHODS It was a prospective, hospital-based observational study. All patients with chronic hepatitis C genotype 3 treated with SOF/LED were divided into two groups: patients with cirrhosis and without cirrhosis. Patients without cirrhosis received SOF/LED (90/400 mg) for 12 weeks; however, patients with cirrhosis received treatment for 24 weeks. RESULTS We enrolled 104 patients with chronic hepatitis C over a period of 24 months. Of the total, 66 were women (63.5%) and 38 were men (36.5%). The average age was 40 years (range: 18-76 years). Of 104 patients, 86 (82.7%) were of genotype 3, 15 (14.9%) were of genotype 1 and 3 (2.9%) were of genotype 4. Ninety-two (88%) were noncirrhotic and 12 (11.5%) were cirrhotic. Ninety-five (95.2%) were treatment naïve. Among genotype 1 and 4, all patients achieved rapid virologic response and SVR 12. Of 86 genotype 3 patients, 78 (90.6%) were noncirrhotic and 8 (9.3%) were cirrhotic. Among genotype 3 patients without cirrhosis, 75 (96%) achieved SVR 12 while 6 (75%) with cirrhosis achieved SVR 12. All patients tolerated the combination well; however, some patients experienced nausea (26%), headache (25%) and fatigue (21%). No patient had to discontinue therapy due to adverse drug reactions. CONCLUSIONS Single tablet LED and SOF combination is safe and effective in genotype 3 patients without cirrhosis even without ribavirin. Being effective in genotype 3, the combination can be used as a pangenotypic drug in patients without cirrhosis.
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Affiliation(s)
- Gulzar A. Dar
- Department of Gastroenterology, SKIMS, Srinagar, India
| | | | | | | | - Suresh Gorka
- Department of Gastroenterology, SKIMS, Srinagar, India
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Galli A, Ramirez S, Bukh J. Lipid Droplets Accumulation during Hepatitis C Virus Infection in Cell-Culture Varies among Genotype 1-3 Strains and Does Not Correlate with Virus Replication. Viruses 2021; 13:389. [PMID: 33671086 PMCID: PMC7999684 DOI: 10.3390/v13030389] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 02/22/2021] [Accepted: 02/24/2021] [Indexed: 12/26/2022] Open
Abstract
Liver steatosis is a common complication of chronic hepatitis C virus (HCV) infection, which can result in accelerated liver fibrosis development, especially in patients infected with genotype 3a. The precise mechanisms of HCV-induced liver steatosis remain unclear, but it is often posited that increased intracellular lipid accumulation is the underlying cause of steatosis. To study experimentally how HCV infection in human liver derived cells by different genotypes and subtypes might affect lipid accumulation, we performed detailed cytofluorimetric and microscopy analyses of intracellular lipid droplets (LDs) in relation to the viral Core and to cell endoplasmic reticulum proteins. Following culture infection with HCV genotype 1a, 2a, 2b, 2c, and 3a strains, we found variable levels of intracellular LDs accumulation, associated to the infecting strain rather than to the specific genotype. Although two genotype 3a strains showed high levels of lipid accumulation, as previously observed, some strains of other genotypes displayed a similar phenotype. Moreover, the analyses of LDs size, number, and shape indicated that the apparent increase in lipid accumulation is due to an increase in the overall number rather than in the size of droplets. Finally, differences in total lipid content across genotypes did not correlate to differences in Core distribution nor Core levels. In conclusion, our study provides a quantitative in-depth analysis of the effect of HCV infection on LDs accumulation in cell-culture.
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Affiliation(s)
- Andrea Galli
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital, 2650 Hvidovre, Denmark; (A.G.); (S.R.)
- Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Santseharay Ramirez
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital, 2650 Hvidovre, Denmark; (A.G.); (S.R.)
- Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Jens Bukh
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital, 2650 Hvidovre, Denmark; (A.G.); (S.R.)
- Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
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Barré T, Rojas Rojas T, Lacombe K, Protopopescu C, Poizot-Martin I, Nishimwe ML, Zucman D, Esterle L, Billaud E, Aumaitre H, Bouchaud O, Rey D, Piroth L, Salmon-Ceron D, Wittkop L, Sogni P, Carrieri MP, Serfaty L, Marcellin F. Cannabis use and reduced risk of elevated fatty liver index in HIV-HCV co-infected patients: a longitudinal analysis (ANRS CO13 HEPAVIH). Expert Rev Anti Infect Ther 2021; 19:1147-1156. [PMID: 33538612 DOI: 10.1080/14787210.2021.1884545] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background: Cannabis use and elevated fatty liver index (FLI≥ 60) (a biomarker of hepatic steatosis in the general population) have been identified as predictors of HCV-related and overall mortality, respectively, in HIV-HCV co-infected patients. However, the relationship between cannabis use and the risk of elevated FLI has never been explored.Methods: Using five-year follow-up data from 997 HIV-HCV co-infected patients (ANRS CO13 HEPAVIH cohort), we analyzed the relationship between cannabis use and FLI using mixed-effects multivariable logistic (outcome: elevated FLI yes/no) and linear (outcome: continuous FLI) regression models.Results: At the last follow-up visit, 27.4% of patients reported regular or daily cannabis use and 27.8% had elevated FLI. After multivariable adjustment, regular or daily cannabis use was associated with a 55% lower risk of elevated FLI (adjusted odds ratio [95% confidence interval]: 0.45 [0.22; 0.94]; p = 0.033) and lower FLI values (adjusted model coefficient: -4.24 [-6.57; -1.91], p < 0.0001).Conclusions: Cannabis use is associated with a reduced risk of elevated fatty liver index in HIV-HCV co-infected patients. Further research is needed to confirm whether and how cannabinoids may inhibit the development of hepatic steatosis or other metabolic disorders in high-risk populations.
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Affiliation(s)
- Tangui Barré
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales De La Santé & Traitement De l'Information Médicale, Marseille, France.,Ors Paca, Observatoire Régional De La Santé Provence-Alpes-Côte d'Azur, Marseille, France
| | - Teresa Rojas Rojas
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales De La Santé & Traitement De l'Information Médicale, Marseille, France.,Ors Paca, Observatoire Régional De La Santé Provence-Alpes-Côte d'Azur, Marseille, France.,APHM Sainte-Marguerite, Clinical Immunohematology Unit, Aix Marseille University, Marseille, France
| | - Karine Lacombe
- Infectious and Tropical Disease Unit, Paris Public Hospitals, Saint-Antoine Hospital, Paris, France.,UMR S1136, Pierre Louis Epidemiology and Public Health Institute, Pierre and Marie Curie University, Paris, France
| | - Camelia Protopopescu
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales De La Santé & Traitement De l'Information Médicale, Marseille, France.,Ors Paca, Observatoire Régional De La Santé Provence-Alpes-Côte d'Azur, Marseille, France
| | - Isabelle Poizot-Martin
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales De La Santé & Traitement De l'Information Médicale, Marseille, France.,APHM Sainte-Marguerite, Clinical Immunohematology Unit, Aix Marseille University, Marseille, France
| | - Marie Libérée Nishimwe
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales De La Santé & Traitement De l'Information Médicale, Marseille, France.,Ors Paca, Observatoire Régional De La Santé Provence-Alpes-Côte d'Azur, Marseille, France
| | - David Zucman
- Department of Internal Medicine, Réseau Ville Hôpital Val De Seine, Foch Hospital, Suresnes, France
| | - Laure Esterle
- Univ. Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, Team MORPH3EUS, UMR 1219, Bordeaux, France
| | - Eric Billaud
- Department of Infectious Disease, CHU Hôtel-Dieu, Nantes, France.,COREVIH Pays De La Loire, CHU Hôtel-Dieu, Nantes, France
| | - Hugues Aumaitre
- Infectious and Tropical Disease Unit, Perpignan Hospital Center, Perpignan, France
| | - Olivier Bouchaud
- Infectious and Tropical Disease Unit, Paris Public Hospitals, Avicenne Hospital, Bobigny, France.,Laboratoire d'Educations et Pratiques en Santé EA 3412, Université Sorbonne Paris Nord, Bobigny, France
| | - David Rey
- Le Trait d'Union, HIV-Infection Care Center, Hôpitaux Universitaires De Strasbourg, Strasbourg, France
| | - Lionel Piroth
- Department of Infectiology, Dijon University Hospital Center, Dijon, France.,INSERM-CIC 1342, Bourgogne University, Dijon, France
| | - Dominique Salmon-Ceron
- Service Maladies Infectieuses Et Tropicales, AP-HP, Hôpital Cochin, Paris, France.,Université Paris Descartes, Paris, France
| | - Linda Wittkop
- Univ. Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, Team MORPH3EUS, UMR 1219, Bordeaux, France.,Pole De Sante Publique, CHU De Bordeaux, Bordeaux, France
| | - Philippe Sogni
- Université Paris Descartes, Paris, France.,INSERM U-1223, Institut Pasteur, Paris, France.,Service d'Hépatologie, Hôpital Cochin, Assistance Publique - Hôpitaux De Paris, France
| | - Maria Patrizia Carrieri
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales De La Santé & Traitement De l'Information Médicale, Marseille, France.,Ors Paca, Observatoire Régional De La Santé Provence-Alpes-Côte d'Azur, Marseille, France
| | - Lawrence Serfaty
- Service d'Hépato-gastroentérologie, Hôpital Hautepierre, Hôpitaux Universitaires De Strasbourg, France.,INSERM UMR 938, Université Paris Sorbonne, Paris, France
| | - Fabienne Marcellin
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales De La Santé & Traitement De l'Information Médicale, Marseille, France.,Ors Paca, Observatoire Régional De La Santé Provence-Alpes-Côte d'Azur, Marseille, France
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Iossa D, Vitrone M, Gagliardi M, Falco E, Ragone E, Zampino R, Durante-Mangoni E. Anthropometric parameters and liver histology influence lipid metabolic changes in HCV chronic hepatitis on direct-acting antiviral treatment. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:35. [PMID: 33553328 PMCID: PMC7859777 DOI: 10.21037/atm-20-669] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background Hepatitis C virus (HCV) infection affects lipid metabolism. We investigated the impact of direct-acting antiviral (DAA) treatment on lipid metabolism in chronic hepatitis C (CHC), with a focus on the effects of anthropometric parameters and liver histology. We also analyzed the dynamics of metabolic indexes used to estimate cardiovascular risk. Methods In 49 patients with CHC treated with DAAs, lipid metabolic changes, anthropometric parameters, liver histology and cardiovascular risk indexes, including triglyceride to HDL ratio (Tr/HDL), fatty liver index (FLI) and visceral adiposity index (VAI) were evaluated at baseline (BL), end of treatment (EOT) and 12 [sustained virological response (SVR) 12] and 24 (SVR24) weeks after EOT. Results SVR occurred in 96% of cases. Total and LDL cholesterol and ApoB levels increased significantly between BL and EOT (P<0.001, <0.001 and 0.05, respectively) and remained stable thereafter. Total and LDL cholesterol significantly increased only in patients with higher BL waist circumference (P<0.01 and 0.009), fibrosis (P=0.002 and 0.005) and steatosis (P=0.043 and 0.033, respectively). HDL cholesterol significantly rose at SVR24. However, cardiovascular risk indexes (Tr/HDL ratio, FLI and VAI) did not significantly change during DAA treatment and follow up. Conclusions Patients with HCV eradication after DAA treatment develop a pro-atherogenic lipid pattern, which varies according to anthropometric parameters and liver histology. However, no increase of cardiovascular risk indexes occurs in the short-term. Total and LDL cholesterol should be monitored long-term in CHC patients cured from infection.
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Affiliation(s)
- Domenico Iossa
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Martina Vitrone
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Massimo Gagliardi
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Erasmo Falco
- Units of Infectious & Transplant Medicine AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Enrico Ragone
- Units of Infectious & Transplant Medicine AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Rosa Zampino
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy.,Units of Infectious & Transplant Medicine AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Emanuele Durante-Mangoni
- Internal Medicine, University of Campania "L. Vanvitelli", Naples, Italy.,Units of Infectious & Transplant Medicine AORN dei Colli, Monaldi Hospital, Naples, Italy
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