|
1
|
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.
Collapse
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
| |
Collapse
|
|
2
|
Wang K, Zhang J, Wang J, Wang M, Yu Y. Role of multiparametric US in the preoperative assessment of hepatic parenchyma in patients with liver tumors. Abdom Radiol (NY) 2025; 50:656-667. [PMID: 39152231 DOI: 10.1007/s00261-024-04386-6] [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: 04/18/2024] [Revised: 05/11/2024] [Accepted: 05/14/2024] [Indexed: 08/19/2024]
Abstract
OBJECTIVES The aim of this study was to evaluate the diagnostic performance of shear wave elastography (SWE), shear wave dispersion (SWD), and attenuation imaging (ATI) in assessment of hepatic parenchyma in patients with liver tumors before resection. METHODS Patients with liver tumors were prospectively enrolled in this study. All participants underwent SWE, SWD, and ATI examinations. Fibrosis stage, necroinflammatory activity and hepatic steatosis grade were determined histopathologically. We evaluated the stability of ATI, SWE and SWD examinations. Multivariable linear regression analyses were conducted to determine the determinant factors for SWE, SWD, attenuation coefficient (AC) values. A receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic performance of multiparametric US (ultrasond). RESULTS A total of 280 participants were enrolled in this study. TG (triglyceride) and steatosis for AC value were significant determinant factors. PLT (platelet), PT (prothrombin time), GGT (glutamyl transpeptidase), and fibrosis stage for SWE value were significant determinant factors. PLT, fibrosis stage and inflammation activity for SWD value were significant determinant factors. AC value was correlated with hepatic steatosis. Both SWE and SWD values were correlated with fibrosis stage, inflammation activity, respectively. The area under the ROC (AUROC) curve of ATI for predicting hepatic steatosis grade were 0.910(≥ S1), 0.927(≥ S2), 0.962(= S3), respectively. The AUROC curve of SWE for predicting fibrosis stage were 0.923(≥ S1), 0.934(≥ S2), 0.930(≥ S3), 0.895(= S4), respectively. The AUROC curve of SWD for predicting fibrosis stage were 0.858(≥ S1), 0.886(≥ S2), 0.866(≥ S1) (≥ S3), 0.825(= S4). The AUROC curve of SWE for predicting inflammation activity were 0.846(≥ G1), 0.724(≥ G2), 0.787 (≥ G3), respectively. The AUROC curve of SWD for predicting inflammation activity were 0.777(≥ G1), 0.727(≥ G2), 0.803 (≥ G3), respectively. CONCLUSIONS For patients with liver tumors, ATI technology showed excellent feasibility and diagnostic performance for detecting and grading hepatic steatosis, SWE was more accurate in detecting fibrosis stage than SWD, SWD was not superior to SWE in detecting inflammation activity.
Collapse
Affiliation(s)
- Kun Wang
- Department of Ultrasound, Binzhou Medical University Hospital, 2 Huanghe Road, Shixi District, Binzhou, 256600, China
| | - Jinqiao Zhang
- Department of Ultrasound, Binzhou Medical University Hospital, 2 Huanghe Road, Shixi District, Binzhou, 256600, China
| | - Jing Wang
- Department of Ultrasound, Binzhou Medical University Hospital, 2 Huanghe Road, Shixi District, Binzhou, 256600, China
| | - Min Wang
- Department of Ultrasound, Binzhou Medical University Hospital, 2 Huanghe Road, Shixi District, Binzhou, 256600, China
| | - Yanjie Yu
- Department of Ultrasound, Binzhou Medical University Hospital, 2 Huanghe Road, Shixi District, Binzhou, 256600, China.
| |
Collapse
|
|
3
|
Gnanapandithan K, Stemboroski L, Johnston A, Ghali MP. Distribution and inflammatory potential of hepatitis C virus genotypes in the United States, 2011-2020. JGH Open 2024; 8:e70049. [PMID: 39502163 PMCID: PMC11533706 DOI: 10.1002/jgh3.70049] [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: 08/03/2024] [Revised: 09/24/2024] [Accepted: 10/17/2024] [Indexed: 11/08/2024]
Abstract
HCV is marked by genetic diversity that impacts disease progression and outcome. Using the NHANES data from 266 HCV-infected adults (2011-2020), this study infers that genotype 1a is the most prevalent (60.2%). Genotype 3 was associated with higher transaminase levels, though not statistically significant. These findings suggest a more aggressive phenotype for genotype 3. Despite pan-genotypic treatment guidelines, this underscores the importance of continued HCV genotype surveillance and consideration for genotype-specific treatment and monitoring strategies.
Collapse
Affiliation(s)
| | - Lauren Stemboroski
- Division of Gastroenterology and HepatologyUniversity of FloridaJacksonvilleFloridaUSA
| | - Abbey Johnston
- Division of Gastroenterology and HepatologyUniversity of FloridaJacksonvilleFloridaUSA
| | - Maged P. Ghali
- Division of Gastroenterology and HepatologyUniversity of FloridaJacksonvilleFloridaUSA
| |
Collapse
|
|
4
|
Stroffolini T, Stroffolini G. A Historical Overview on the Role of Hepatitis B and C Viruses as Aetiological Factors for Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:cancers15082388. [PMID: 37190317 DOI: 10.3390/cancers15082388] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/14/2023] [Accepted: 04/19/2023] [Indexed: 05/17/2023] Open
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the leading cause of hepatocellular carcinoma (HCC) worldwide. Currently, HBV-related HCC predominates in Sub-Saharan Africa and South-East-Asia, while HCV-related HCC predominates in northern Africa and in the western world. Liver cirrhosis is the underlying condition in most HBV cases and in nearly all HCV cases. Several cofactors, viral and non-viral, play a role in the progression toward HCC: dual HBV/HCV infection, HDV, HIV, alcohol intake, smoking, diabetes mellitus, obesity, and NAFLD/NASH. HBV vaccine is effective in preventing both infection and HCC; antiviral drugs may suppress HBV replication and eradicate HCV infection, halting progression to HCC. Inequalities exist between high- and low-income countries with respect to vaccine availability and access to antivirals. These factors represent barriers to the control of HCC incidence. Lack of an effective vaccine against HCV is also a serious barrier to HCV elimination and HCC prevention. The most crucial steps and knowledge that have arisen over time on the association between the two major hepatotropic viruses and HCC are discussed in this historical review.
Collapse
Affiliation(s)
- Tommaso Stroffolini
- Department of Tropical and Infectious Diseases, Policlinico Umberto I, 00161 Rome, Italy
| | - Giacomo Stroffolini
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni, 5, Negrar, 37024 Verona, Italy
| |
Collapse
|
|
5
|
Huang S, Wu H, Luo F, Zhang B, Li T, Yang Z, Ren B, Yin W, Wu D, Tai S. Exploring the role of mast cells in the progression of liver disease. Front Physiol 2022; 13:964887. [PMID: 36176778 PMCID: PMC9513450 DOI: 10.3389/fphys.2022.964887] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 07/28/2022] [Indexed: 11/22/2022] Open
Abstract
In addition to being associated with allergic diseases, parasites, bacteria, and venoms, a growing body of research indicates that mast cells and their mediators can regulate liver disease progression. When mast cells are activated, they degranulate and release many mediators, such as histamine, tryptase, chymase, transforming growth factor-β1 (TGF-β1), tumor necrosis factor–α(TNF-α), interleukins cytokines, and other substances that mediate the progression of liver disease. This article reviews the role of mast cells and their secretory mediators in developing hepatitis, cirrhosis and hepatocellular carcinoma (HCC) and their essential role in immunotherapy. Targeting MC infiltration may be a novel therapeutic option for improving liver disease progression.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - Dehai Wu
- *Correspondence: Sheng Tai, ; Dehai Wu,
| | - Sheng Tai
- *Correspondence: Sheng Tai, ; Dehai Wu,
| |
Collapse
|
|
6
|
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.
Collapse
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
| |
Collapse
|
|
7
|
Lesmana CRA, Kencana Y, Rinaldi I, Kurniawan J, Hasan I, Sanityoso Sulaiman A, Gani RA. Diagnostic Value of Neutrophil to Lymphocyte Ratio in Non-Alcoholic Fatty Liver Disease Evaluated Using Transient Elastography (TE) with Controlled Attenuated Parameter (CAP). Diabetes Metab Syndr Obes 2022; 15:15-22. [PMID: 35023936 PMCID: PMC8743379 DOI: 10.2147/dmso.s330526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 11/30/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a chronic inflammatory disease with excessive fat accumulation in the liver. Transient elastography (TE) with controlled attenuation parameter (CAP) is a device and method to examine the degree of fibrosis and steatosis. However, this device is not widely available across Indonesia. Neutrophil and lymphocyte ratio (NLR) is a simple marker for inflammation, which has a potency to predict disease outcome. This study aims to know the diagnostic value of NLR as the indicator of steatosis and fibrosis severity. METHODS This was a cross-sectional study with consecutive sample collection. We used secondary data from medical records, starting from 2016 to 2018. A descriptive and data analysis, including correlation test, multivariate linear regression, t-test, receiver operating curve (ROC) and area under the curve (AUC) were done to find out the outcome of the study. Statistical analyses were performed using Statistical Package for Social Sciences (SPSS) Version 20.0 (SPSS Inc, Chicago, Illinois). A P value <0.05 was considered as statistically significant. RESULTS Out of 106 subjects, 62.3% patients were women with the mean of age 57.29 years old and 77.4% had metabolic syndrome. Most patients had moderate to severe steatosis degree (66%) with the mean of TE mean 6.14 (2.8-18.2) kPa. There was a positive correlation between CAP and TE compared with NLR with r = 0.648 (p < 0.001) and r = 0.621 (p < 0.001), respectively. The use of RNL to assess moderate-severe steatosis has a cutoff point of 1.775 with sensitivity, specificity, PPV and NPV, respectively, at 81.5%, 80.6%, 89.1%, and 69.1%; cutoff point 2.150 to assess significant fibrosis with sensitivity, specificity, PPV and NPV of 92.3%, 87.5%, 70.6%, and 97.2%, respectively. CONCLUSION NLR has a positive and significant correlation with the degree of steatosis and fibrosis with high sensitivity and specificity as evaluated by TE/CAP.
Collapse
Affiliation(s)
- Cosmas Rinaldi Adithya Lesmana
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
- Digestive Disease & GI Oncology Center, Medistra Hospital, Jakarta, Indonesia
| | - Yoppi Kencana
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Ikhwan Rinaldi
- Department of Internal Medicine, Haematology and Oncology Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Juferdy Kurniawan
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Irsan Hasan
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Andri Sanityoso Sulaiman
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Rino Alvani Gani
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| |
Collapse
|
|
8
|
Kim MN, Han K, Yoo J, Hwang SG, Ahn SH. Increased risk of hepatocellular carcinoma and mortality in chronic viral hepatitis with concurrent fatty liver. Aliment Pharmacol Ther 2022; 55:97-107. [PMID: 34820871 DOI: 10.1111/apt.16706] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 08/13/2021] [Accepted: 11/07/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Population-based data are lacking regarding whether fatty liver is a risk factor for hepatocellular carcinoma (HCC) and mortality in patients with chronic viral hepatitis. AIM To investigate the association of fatty liver with HCC incidence and mortality in patients with chronic viral hepatitis using a nationwide cohort METHODS: We included 57,385 patients with chronic hepatitis B (CHB) or chronic hepatitis C (CHC) who underwent health examinations. The patients were divided into three groups: no fatty liver, fatty liver index (FLI) <30, grade 1 (G1) fatty liver: 30≤ FLI <60, and grade 2 (G2) fatty liver: FLI >60. RESULTS During a median 8.4-year follow-up, we documented 3496 HCC cases and 4146 deaths. Compared to patients with no fatty liver (n = 35,018), the risk of HCC was significantly higher in patients with G1 fatty liver (n = 14,544) (adjusted hazard ratio [aHR] = 1.50, 95% confidence interval [CI] = 1.38-1.64) and G2 fatty liver (n = 7,823) (aHR = 1.88, 95% CI = 1.67-2.12). The risk of mortality was significantly higher in patients with G1 fatty liver (aHR = 1.53, 95% CI = 1.41-1.66) and G2 fatty liver (aHR = 2.16, 95% CI = 1.94-2.42) compared to patients with no fatty liver. CONCLUSIONS Concurrent fatty liver was associated with a higher risk of HCC and mortality in patients with chronic viral hepatitis. Our results suggest the importance of management of fatty liver to reduce the risks of HCC and mortality in patients with chronic viral hepatitis.
Collapse
Affiliation(s)
- Mi Na Kim
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea.,Clinical and Translational Hepatology Laboratory, Seongnam, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Juhwan Yoo
- Department of Biomedicine & Health Science, The Catholic University of Korea, Seoul, Korea
| | - Seong Gyu Hwang
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
9
|
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.
Collapse
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
| |
Collapse
|
|
10
|
Jang JK, Kim SY, Yoo IW, Cho YB, Kang HJ, Lee DH. Diagnostic performance of ultrasound attenuation imaging for assessing low-grade hepatic steatosis. Eur Radiol 2021; 32:2070-2077. [PMID: 34549325 DOI: 10.1007/s00330-021-08269-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 08/03/2021] [Accepted: 08/11/2021] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To investigate the diagnostic performance of attenuation imaging (ATI) for the assessment of low-grade hepatic steatosis using liver biopsy as the reference standard. METHODS The study included 57 potential donor candidates for living liver transplantation who underwent ATI, transient elastography (TE), and liver biopsy for evaluation of hepatic steatosis between February 2020 and April 2020. The attenuation coefficient (AC) from ATI and the controlled attenuation parameter (CAP) from TE were measured for each participant in a random and blind manner. The histologic hepatic fat fraction (HFF) was graded (S0, < 5%; S1, 5-33%; S2, 33-66%; S3, > 66%). The accuracy of ATI for diagnosing hepatic steatosis was compared with that of CAP using ROC analysis. Correlations between AC and HFF were evaluated, and factors affecting AC were determined by linear regression analysis. RESULTS The median HFF was 3% (range: 0-35%), with 31 (54.4%), 24 (42.0%), and 2 (3.5%) participants being graded as S0, S1, and S2, respectively. The AUCs for the ROCs of AC and CAP for the detection of hepatic steatosis were 0.808 (95% CI: 0.682-0.900) and 0.829 (95% CI: 0.706-0.916), respectively, with the difference not being statistically significant (p = 0.762). AC showed 61.5% of sensitivity and 90.3% of specificity. AC was positively correlated with HFF (p < 0.001). HFF was the only factor significantly affecting AC. CONCLUSIONS ATI showed moderate sensitivity and high specificity in the diagnosis and quantification of hepatic steatosis in low-grade steatosis without fibrosis. Only HFF significantly affected AC. KEY POINTS • Attenuation imaging showed moderate sensitivity and high specificity performance in the diagnosis and quantification of hepatic steatosis in low-grade steatosis without fibrosis. • The diagnostic performance of the attenuation coefficient by attenuation imaging did not significantly differ from that of the controlled attenuation parameter by transient elastography in quantifying low-grade steatosis. • The histopathologically determined hepatic fat fraction was the only factor significantly affecting the attenuation coefficient.
Collapse
Affiliation(s)
- Jong Keon Jang
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
| | - In Woon Yoo
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Young Bum Cho
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Hyo Jeong Kang
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea
| |
Collapse
|
|
11
|
Florea M, Serban T, Tirpe GR, Tirpe A, Lupsor-Platon M. Noninvasive Assessment of Hepatitis C Virus Infected Patients Using Vibration-Controlled Transient Elastography. J Clin Med 2021; 10:jcm10122575. [PMID: 34200885 PMCID: PMC8230562 DOI: 10.3390/jcm10122575] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/06/2021] [Accepted: 06/08/2021] [Indexed: 02/08/2023] Open
Abstract
Chronic infection with hepatitis C virus (HCV) is one of the leading causes of cirrhosis and hepatocellular carcinoma (HCC). Surveillance of these patients is an essential strategy in the prevention chain, including in the pre/post-antiviral treatment states. Ultrasound elastography techniques are emerging as key methods in the assessment of liver diseases, with a number of advantages such as their rapid, noninvasive, and cost-effective characters. The present paper critically reviews the performance of vibration-controlled transient elastography (VCTE) in the assessment of HCV patients. VCTE measures liver stiffness (LS) and the ultrasonic attenuation through the embedded controlled attenuation parameter (CAP), providing the clinician with a tool for assessing fibrosis, cirrhosis, and steatosis in a noninvasive manner. Moreover, standardized LS values enable proper staging of the underlying fibrosis, leading to an accurate identification of a subset of HCV patients that present a high risk for complications. In addition, VCTE is a valuable technique in evaluating liver fibrosis prior to HCV therapy. However, its applicability in monitoring fibrosis regression after HCV eradication is currently limited and further studies should focus on extending the boundaries of VCTE in this context. From a different perspective, VCTE may be effective in identifying clinically significant portal hypertension (CSPH). An emerging prospect of clinical significance that warrants further study is the identification of esophageal varices. Our opinion is that the advantages of VCTE currently outweigh those of other surveillance methods.
Collapse
Affiliation(s)
- Mira Florea
- Community Medicine Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Teodora Serban
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - George Razvan Tirpe
- Department of Radiology and Medical Imaging, County Emergency Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400000 Cluj-Napoca, Romania;
| | - Alexandru Tirpe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania;
| | - Monica Lupsor-Platon
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
- Medical Imaging Department, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
- Correspondence:
| |
Collapse
|
|
12
|
Semmler G, Binter T, Kozbial K, Schwabl P, Chromy D, Bauer D, Simbrunner B, Müllner-Bucsics T, Scheiner B, Stättermayer A, Pinter M, Steindl-Munda P, Trauner M, Ferenci P, Reiberger T, Mandorfer M. Influence of Genetic Variants on Disease Regression and Outcomes in HCV-Related Advanced Chronic Liver Disease after SVR. J Pers Med 2021; 11:281. [PMID: 33917196 PMCID: PMC8067986 DOI: 10.3390/jpm11040281] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/03/2021] [Accepted: 04/05/2021] [Indexed: 12/11/2022] Open
Abstract
Genetic variants including PNPLA3-rs738409 C>G, TM6SF2-rs58542926 C>T, MBOAT7-rs641738 C>T, and HSD17B13-rs72613567 T>TA have been shown to influence progression to advanced chronic liver disease (ACLD) in patients with chronic hepatitis C (CHC). We aimed to investigate their impact on disease regression (i.e., changes in hepatic venous pressure gradient [HVPG] and non-invasive surrogates [liver stiffness measurement (LSM), von Willebrand factor (VWF), and VWF/platelet count ratio (VITRO)]) and clinical outcomes after CHC cure in 346 patients with pre-treatment ACLD. Patients carrying the PNPLA3 minor allele had more advanced liver disease prior to antiviral therapy, confirming its impact on liver disease progression. In a subgroup of 88 patients who underwent paired HVPG-measurements and were genotyped for all SNP/indels, PNPLA3/TM6SF2/MBOAT7/HSD17B13 genotypes were not associated with changes in HVPG. In line, changes in non-invasive surrogates of portal hypertension (LSM/VWF/VITRO) were comparable between carriers and non-carriers of the PNPLA3 G-allele in the overall cohort. Finally, carriage of PNPLA3 G-allele was not associated with the development of hepatic decompensation, de-novo hepatocellular carcinoma, or transplant-free mortality during a median follow-up of 42 months after the end of antiviral treatment. Therefore, genetic variants in PNPLA3/TM6SF2/MBOAT7/HSD17B13 do not impact the regression of portal hypertension and clinical outcomes in patients with pre-treatment ACLD after CHC cure.
Collapse
Affiliation(s)
- Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, 1090 Vienna, Austria
| | - Teresa Binter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, 1090 Vienna, Austria
| | - Karin Kozbial
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, 1090 Vienna, Austria
| | - David Chromy
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
| | - David Bauer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, 1090 Vienna, Austria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, 1090 Vienna, Austria
| | - Theresa Müllner-Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, 1090 Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, 1090 Vienna, Austria
| | - Albert Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, 1090 Vienna, Austria
| | - Matthias Pinter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, 1090 Vienna, Austria
| | - Petra Steindl-Munda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
| | - Peter Ferenci
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, 1090 Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (G.S.); (T.B.); (K.K.); (P.S.); (D.C.); (D.B.); (B.S.); (T.M.-B.); (B.S.); (A.S.); (M.P.); (P.S.-M.); (M.T.); (P.F.); (M.M.)
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, 1090 Vienna, Austria
| |
Collapse
|
|
13
|
Cabral B, Hoffmann L, Bottaro T, Costa P, Ramos A, Coelho H, Villela-Nogueira C, Ürményi T, Faffe D, Silva R. Circulating microRNAs associated with liver fibrosis in chronic hepatitis C patients. Biochem Biophys Rep 2020; 24:100814. [PMID: 33015376 PMCID: PMC7520427 DOI: 10.1016/j.bbrep.2020.100814] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 09/06/2020] [Accepted: 09/14/2020] [Indexed: 12/21/2022] Open
Abstract
A major challenge in hepatitis C research is the detection of early potential for progressive liver disease. MicroRNAs (miRNAs) are small RNAs that regulate gene expression and can be biomarkers of pathological processes. In this study, we compared circulating miRNAs identified in hepatitis C virus (HCV)-infected patients presenting two extremes of liver disease: mild/moderate fibrosis and cirrhosis. The patients in the cirrhosis group subsequently developed hepatocellular carcinoma (HCC). We identified 163 mature miRNAs in the mild/moderate fibrosis group and 171 in the cirrhosis group, with 144 in common to both groups. Differential expression analysis revealed 5 upregulated miRNAs and 2 downregulated miRNAs in the cirrhosis group relative to the mild/moderate fibrosis group. Functional analyses of regulatory networks (target gene and miRNA) identified gene categories involved in cell cycle biological processes and metabolic pathways related to cell cycle, cancer, and apoptosis. These results suggest that the differentially expressed circulating miRNAs observed in this work (miR-215-5p, miR-483-5p, miR-193b-3p, miR-34a-5p, miR-885-5p, miR-26b-5p and miR -197-3p) may be candidates for biomarkers in the prognosis of liver disease.
Collapse
Affiliation(s)
- B.C.A. Cabral
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - L. Hoffmann
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Departamento de Biotecnologia, Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, Rio de Janeiro, Brazil
| | - T. Bottaro
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - P.F. Costa
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - A.L.A. Ramos
- Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - H.S.M. Coelho
- Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - C.A. Villela-Nogueira
- Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - T.P. Ürményi
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - D.S. Faffe
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - R. Silva
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| |
Collapse
|
|
14
|
Ghosh S, Chakraborty J, Goswami A, Bhowmik S, Roy S, Ghosh A, Dokania S, Kumari P, Datta S, Chowdhury A, Bhattacharyya SN, Chatterjee R, Banerjee S. A novel microRNA boosts hyper-β-oxidation of fatty acids in liver by impeding CEP350-mediated sequestration of PPARα and thus restricts chronic hepatitis C. RNA Biol 2020; 17:1352-1363. [PMID: 32507013 DOI: 10.1080/15476286.2020.1768353] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Imbalance in lipid metabolism induces steatosis in liver during Chronic hepatitis C (CHC). Contribution of microRNAs in regulating lipid homoeostasis and liver disease progression is well established using small RNA-transcriptome data. Owing to the complexity in the development of liver diseases, the existence and functional importance of yet undiscovered regulatory miRNAs in disease pathogenesis was explored in this study using the unmapped sequences of the transcriptome data of HCV-HCC liver tissues following miRDeep2.pl pipeline. MicroRNA-c12 derived from the first intron of LGR5 of chromosome 12 was identified as one of the miRNA like sequences retrieved in this analysis that showed human specific origin. Northern blot hybridization has proved its existence in the hepatic cell line. Enrichment of premiR-c12 in dicer-deficient cells and miR-c12 in Ago2-RISC complex clearly suggested that it followed canonical miRNA biogenesis pathway and accomplished its regulatory function. Expression of this miRNA was quite low in CHC tissues than normal liver implying HCV-proteins might be regulating its biogenesis. Promoter scanning and ChIP analysis further revealed that under expression of p53 and hyper-methylation of STAT3 binding site upon HCV infection restricted its expression in CHC tissues. Centrosomal protein 350 (CEP350), which sequestered PPARα, was identified as one of the targets of miR-c12 using Miranda and validated by luciferase assay/western blot analysis. Furthermore, reduced triglyceride accumulation and enhanced PPARα mediated transcription of β-oxidation genes upon restoration of miR-c12 in liver cells suggested its role in lipid catabolism. Thus this study is reporting miR-c12 for the first time and showed its' protective role during chronic HCV infection.
Collapse
Affiliation(s)
- Suchandrima Ghosh
- Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research , Kolkata, India
| | - Joyeeta Chakraborty
- Human Genetics Unit, Indian Statistical Institute , Kolkata, Human Genetics Unit, India
| | - Avijit Goswami
- Department of Molecular Genetics, Indian Institute of Chemical Biology , Kolkata, India
| | - Sayantani Bhowmik
- Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research , Kolkata, India
| | - Susree Roy
- Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research , Kolkata, India
| | - Amit Ghosh
- Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research , Kolkata, India
| | - Sakshi Dokania
- Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research , Kolkata, India
| | - Priyanka Kumari
- Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research , Kolkata, India
| | - Simanti Datta
- Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research , Kolkata, India
| | - Abhijit Chowdhury
- Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research , Kolkata, India
| | | | - Raghunath Chatterjee
- Human Genetics Unit, Indian Statistical Institute , Kolkata, Human Genetics Unit, India
| | - Soma Banerjee
- Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research , Kolkata, India
| |
Collapse
|
|
15
|
Semmler G, Wöran K, Scheiner B, Unger LW, Paternostro R, Stift J, Schwabl P, Bucsics T, Bauer D, Simbrunner B, Stättermayer AF, Pinter M, Trauner M, Reiberger T, Mandorfer M. Novel reliability criteria for controlled attenuation parameter assessments for non-invasive evaluation of hepatic steatosis. United European Gastroenterol J 2020; 8:321-331. [PMID: 32213023 PMCID: PMC7184665 DOI: 10.1177/2050640619900820] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 12/01/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND There is conflicting evidence regarding reliability criteria for the controlled attenuation parameter (CAP; a marker for hepatic steatosis [HS]). Thus, we assessed the diagnostic performance of CAP according to different reliability criteria based on real-world data from an academic centre. METHODS Patients undergoing measurement of CAP and liver biopsy (±6 months) at the Medical University of Vienna were included. HS was assessed according to SAF score. RESULTS In total 319 patients were included. The main aetiologies were non-alcoholic fatty liver disease (NAFLD, n = 177, 55.5%), viral hepatitis (n = 49, 15.4%), and alcoholic liver disease (ALD, n = 29, 9.1%). Histological steatosis and fibrosis stages were: S0: 93 (29.2%), S1: 100 (31.3%), S2: 67 (21.0%), and S3: 59 (18.5%); F0/F1: 150 (47.0%), F2: 47 (14.7%), and F3/F4: 122 (48.3%). In the overall cohort, the area under the receiver operating characteristic curve (AUC) of CAP was 0.843 (95% confidence interval [CI]: 0.798-0.887) for diagnosing HS ≥ S1), 0.789 (95%CI: 0.740-0.839) for ≥S2, and 0.767 (95%CI: 0.712-0.823) for S3. CAP corrections as suggested by Karlas et al. did not improve the diagnostic performance. Importantly, the AUC of CAP for HS ≥ S1 was numerically highest in patients with CAP-IQR/median<0.10 or <0.20 (obtained in 37.9% and 74.9%), in whom CAP also had better diagnostic performance, as compared with patients not meeting these criteria. Moreover, it was substantially higher in 288 (90.3%) patients with CAP-IQR/median<0.3: 0.856 (95%CI: 0.809-0.903) vs. patients not meeting this criterion (0.530 [95%CI: 0.309-0.751]). In contrast, the previously suggested reliability criterion of CAP-IQR<40 dB/m was not associated with an improved diagnostic performance for HS≥S1 (0.866 [95%CI: 0.812-0.920] vs. 0.799 [95%CI: 0.717-0.881]) and was only obtained in 199 (62.4%) patients. CONCLUSION CAP-IQR/median<0.1, <0.2, and <0.3 identify reliable measurements for diagnosing any hepatic steatosis (≥S1). Importantly, CAP-IQR/median<0.3 has a considerably higher applicability in clinical practice, as compared with the previously suggested CAP-IQR<40 dB/m criterion.
Collapse
Affiliation(s)
- Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Katharina Wöran
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Lukas Walter Unger
- Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Rafael Paternostro
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Judith Stift
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - David Bauer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Matthias Pinter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
16
|
Semmler G, Stift J, Scheiner B, Wöran K, Schwabl P, Paternostro R, Bucsics T, Stättermayer AF, Pinter M, Ferlitsch A, Trauner M, Reiberger T, Mandorfer M. Performance of Controlled Attenuation Parameter in Patients with Advanced Chronic Liver Disease and Portal Hypertension. Dig Dis Sci 2019; 64:3642-3651. [PMID: 31209721 PMCID: PMC6858384 DOI: 10.1007/s10620-019-05702-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2019] [Accepted: 06/04/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Liver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) is influenced by liver fibrosis and hepatic perfusion pressure. VCTE-based controlled attenuation parameter (CAP) is a noninvasive marker for hepatic steatosis (HS). AIMS To investigate the diagnostic performance of CAP in patients with advanced chronic liver disease (ACLD)/portal hypertension (PHT: hepatic venous pressure gradient (HVPG) ≥ 6 mmHg). METHODS Eighty-eight patients with LS ≥ 10 kPa and/or HVPG ≥ 6 mmHg who underwent simultaneous liver biopsy, CAP, and HVPG measurement were included. HS was histologically graded according to the modified Brunt classification. RESULTS Patient characteristics: Mean MELD:11 (standard derivation [SD] ± 4), median HVPG:16 (interquartile range [IQR]10-19) mmHg, median LS:27.4 (IQR 16.2-48.9) kPa, and mean CAP:221 (SD ± 75) dB/m. According to histology, 47 (53.4%) patients had no HS (S0), 28 (31.8%) had S1, 11 (12.5%) had S2, and 2 (2.3%) had S3. The area under the receiver operating characteristic curve (AUROC) of CAP for diagnosing any HS (S0 vs. ≥ S1) was 0.692 (95% confidence interval [95% CI] 0.582-0.802) in the overall cohort, 0.830 (95% CI 0.637-1.0) in patients with HVPG < 10 mmHg, and 0.629 (95% CI 0.497-0.761) in patients with clinically significant portal hypertension (CSPH; HVPG ≥ 10 mmHg; n = 69). Using the established cutoff for any HS (248 dB/m), the sensitivity/specificity of CAP was only 48.8%/76.6%, respectively. In contrast, the AUROC and sensitivity/specificity (cutoff 268 dB/m) for diagnosing HS ≥ S2 were 0.842 (95% CI 0.747-0.936) and 84.6%/81.3%, respectively. CAP correlated with the percentage of steatotic hepatocytes (Spearman's ρ = 0.402; p ≤ 0.001) and showed a weak correlation with liver stiffness (ρ = 0.225; p = 0.035). CONCLUSIONS The diagnostic performance of CAP for any HS seems to be limited in patients with ACLD, if CSPH is present.
Collapse
Affiliation(s)
- Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Judith Stift
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Katharina Wöran
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Rafael Paternostro
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Matthias Pinter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Arnulf Ferlitsch
- Department of Internal Medicine I, Hospital of St. John of God, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
| |
Collapse
|
|
17
|
Mohamed AA, Eljaky AM, Abdelsameea EM, Fouad TR, El-Ezawy HEDM. Prevalence and effect of occult hepatitis C infection in patients with persistent liver enzyme elevation after achieving 24 weeks of sustained virological response. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2019. [DOI: 10.4103/ejim.ejim_24_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
|
|
18
|
Chromy D, Mandorfer M, Bucsics T, Schwabl P, Bauer D, Scheiner B, Schmidbauer C, Lang GF, Szekeres T, Ferenci P, Trauner M, Reiberger T. Prevalence and Predictors of Hepatic Steatosis in Patients with HIV/HCV Coinfection and the Impact of HCV Eradication. AIDS Patient Care STDS 2019; 33:197-206. [PMID: 31067123 DOI: 10.1089/apc.2018.0333] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Human immunodeficiency virus (HIV)-induced metabolic abnormalities and antiretroviral therapy (ART), genetic factors, most importantly the rs738409 C > G p.I148M variant in the patatin-like phospholipase domain containing 3 (PNPLA3)-gene, as well as hepatitis C virus (HCV) coinfection may all cause hepatic steatosis (HS). However, recent studies suggest a protective effect of HCV infection on HS. Thus, we evaluated HS prior and after HCV eradication in an HIV/HCV-coinfected cohort at the Medical University of Vienna between January 2014 and June 2017. Two hundred forty-seven patients underwent liver stiffness measurement and controlled attenuation parameter (CAP)-based steatosis assessment. A subcohort of 138 patients also had follow-up CAP measurement after HCV eradication by direct-acting antivirals (DAAs). A CAP value ≥248 dB/m defined HS and all CAP values were adapted to compensate for body mass index (BMI) and diabetes mellitus. Among all 247 HIV/HCV-coinfected patients, HS was prevalent in 31%, mean age was 43.3 years, 75% were male, the main ethnicity was Caucasian (96%), and mean BMI was 23.33 kg/m2. Independent risk factors for HS were BMI, years exposed to HIV, PNPLA3 G-alleles, and protease inhibitor (PI) intake. Notably, a significant increase in CAP (from 225 ± 52.9 to 235 ± 50.7 dB/m; p = 0.047) was observed after HCV eradication, whereas patients on PI-containing ART experienced a significant decrease in CAP. Overall, one-third of HIV/HCV-coinfected patients are affected by HS with PI-based ART and PNPLA3 impacting on HS prevalence. While HCV eradication by DAAs increased HS, as assessed by CAP, future studies should account for metabolic syndrome and evaluate whether changes in CAP-based steatosis assessments correspond to a clinically relevant outcome.
Collapse
Affiliation(s)
- David Chromy
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - Mattias Mandorfer
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - Theresa Bucsics
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - Philipp Schwabl
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - David Bauer
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - Bernhard Scheiner
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - Caroline Schmidbauer
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - Gerold Felician Lang
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
- 3 Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Thomas Szekeres
- 4 Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Peter Ferenci
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| |
Collapse
|
|
19
|
Sansom SE, Martin J, Adeyemi O, Burke K, Winston C, Markham S, Go B, Huhn G. Steatosis Rates by Liver Biopsy and Transient Elastography With Controlled Attenuation Parameter in Clinical Experience of Hepatitis C Virus (HCV) and Human Immunodeficiency Virus/HCV Coinfection in a Large US Hepatitis Clinic. Open Forum Infect Dis 2019; 6:ofz099. [PMID: 30968054 PMCID: PMC6451651 DOI: 10.1093/ofid/ofz099] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Revised: 02/12/2019] [Accepted: 02/25/2019] [Indexed: 12/21/2022] Open
Abstract
Background Steatosis contributes to liver fibrosis in hepatitis C virus (HCV) and human immunodeficiency virus (HIV)/HCV coinfection. Liver biopsy (LB) is the reference standard for grading steatosis and staging fibrosis, yet recent advances in noninvasive modalities have largely supplanted LB, which may limit recognition of steatosis. We evaluated steatosis rates by LB and transient elastography (TE) with controlled attenuation parameter (CAP) among HCV-infected and HIV/HCV-coinfected patients in a US clinic. Methods Patients with chronic HCV infection during pretreatment evaluation by LB (n = 421; December 2001 through May 2014) and TE with CAP (n = 1157; May 2016 through May 2017) were included. Fibrosis and steatosis rates by LB and TE with CAP were stratified by HCV versus HIV/HCV coinfection status. Results Steatosis was not reported in 26.1% of LBs. Moderate to severe steatosis (grade ≥S2) was detected more often with CAP than with LB (in 24.0% vs 11.4% of patients, respectively). Median CAP values were higher in patients with HCV monoinfection than in those with coinfection (230 vs 215.5 dB/m, respectively; P < .001). With TE, the rate of advanced fibrosis (values F3–F4) was higher in HCV monoinfection than in coinfection (25.9% vs 14.8%, respectively; P <.001). With both LB and TE, advanced fibrosis (F3–F4) was significantly associated with moderate to severe steatosis (S2–S3) in HCV monoinfection compared with HIV/HCV coinfection (33.3% vs 4.4%, respectively for LB [P = 0.003] and 36.0% vs 29.0% for TE [P = 0.008]). Conclusions In patients with chronic HCV undergoing liver fibrosis staging, steatosis was detected more often with CAP than LB, with median CAP values higher in HCV monoinfection than HIV/HCV coinfection. Steatosis severity may be increasing in the modern HCV treatment era.
Collapse
Affiliation(s)
- Sarah E Sansom
- Ruth M. Rothstein CORE Center, Chicago, Illinois.,Rush University Medical Center, Chicago, Illinois
| | - Jonathan Martin
- Ruth M. Rothstein CORE Center, Chicago, Illinois.,Rush University Medical Center, Chicago, Illinois
| | - Oluwatoyin Adeyemi
- Ruth M. Rothstein CORE Center, Chicago, Illinois.,Rush University Medical Center, Chicago, Illinois
| | | | | | - Sara Markham
- Ruth M. Rothstein CORE Center, Chicago, Illinois
| | - Benjamin Go
- Ruth M. Rothstein CORE Center, Chicago, Illinois
| | - Gregory Huhn
- Ruth M. Rothstein CORE Center, Chicago, Illinois.,Rush University Medical Center, Chicago, Illinois
| |
Collapse
|
|
20
|
Yen YH, Lin MT, Kuo FY, Chang KC, Tsai MC, Tseng PL, Wu CK, Lin JT, Hu TH, Lu SN, Wang JH, Hung CH, Chen CH. The association between steatosis and diabetes with hepatocellular carcinoma in non-genotype 3 chronic hepatitis C patients. Liver Int 2018; 38:1064-1073. [PMID: 29164767 DOI: 10.1111/liv.13633] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 11/13/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Diabetes mellitus (DM) has been found to be strongly associated with an increased risk of hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients. Several studies have also found an association between metabolic steatosis and the risk of HCC in CHC patients, whether this latter association has been accounted for by the known relationship between DM and HCC is still unknown. METHODS A cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC and treated with interferon and ribavirin was studied. Cumulative incidence and HCC risk were analysed using the Kaplan-Meier method and Cox proportional hazard analysis. RESULTS Hepatocellular carcinoma developed in 140 subjects over a median follow-up period of 97.3 months, while 699 patients achieved sustained virological response (SVR). According to multivariate analyses, age ≥ 60 years, advanced fibrosis and genotype 1 were identified as independent factors significantly associated with HCC development in SVR patients. Furthermore, using the absence of steatosis and absence of DM as references, the presence of steatosis without DM (HR = 2.09, 95% CI = 1.12-3.9, P = .021), the presence of DM without steatosis (HR = 2.78, 95% CI = 1.3-5.92, P = .008) and the combined presence of steatosis and DM (HR = 3.25, 95% CI = 1.44-7.33, P = .004) were identified as independent factors significantly associated with HCC development in the SVR patients. In contrast, steatosis alone, DM alone and the combined presence of steatosis and DM were not associated with HCC development in non-SVR patients. CONCLUSIONS Steatosis and DM may be associated with HCC development in non-genotype 3 CHC patients with SVR.
Collapse
Affiliation(s)
- Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Tsung Lin
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Fang-Ying Kuo
- Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Chin Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Chao Tsai
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Po-Lin Tseng
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Cheng-Kun Wu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jung-Ting Lin
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| |
Collapse
|
|
21
|
Afsari A, Lee E, Shokrani B, Boortalary T, Sherif ZA, Nouraie M, Laiyemo AO, Alkhalloufi K, Brim H, Ashktorab H. Clinical and Pathological Risk Factors Associated with Liver Fibrosis and Steatosis in African-Americans with Chronic Hepatitis C. Dig Dis Sci 2017; 62:2159-2165. [PMID: 28612194 PMCID: PMC5706543 DOI: 10.1007/s10620-017-4626-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2017] [Accepted: 05/23/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM Several factors involved in the development of liver fibrosis in African-American patients with chronic hepatitis C have not been well studied. We aimed to evaluate some of these risk factors. METHODS We reviewed pathology and medical records of 603 African-Americans with chronic hepatitis C virus (HCV) infection at Howard University Hospital from January 2004 to December 2013. Among the clinical and pathological data collected were HIV (human immunodeficiency virus), HCV genotype, hepatitis B virus (HBV), diabetes mellitus (DM), hypertension (HTN), body mass index (BMI), and hepatic steatosis. RESULTS The frequency of DM, HTN, HIV, and HBV was 22, 16, 11, and 4%, respectively. Median BMI was 27.3 kg/m2. The frequency of fibrosis stages 0, 1, 2, 3, and 4 was 2, 48, 28, 11, and 11%, respectively. In multivariate logistic regression, we found a significant association between liver fibrosis stage (3-4 vs. 0-2) and HIV infection (OR 2.4, P = 0.026), HTN (OR 3.0, P = 0.001), age (OR 2.6 for every 10 years, P < 0.001), weight (OR 1.1 for every 10 lb increase, P = 0.002), and steatosis grade (OR 1.6, P = 0.002). The frequency of liver steatosis was 73%. In an ordinal logistic regression, significant risk factors for steatosis were female gender (OR 1.5, P = 0.034) and inflammation grade (P = 0.001). CONCLUSION This study shows that steatosis is independently associated with fibrosis in African-American patients with HCV infection. Female patients were at higher risk of steatosis.
Collapse
Affiliation(s)
- Ali Afsari
- Department of Medicine and Cancer Research Center, Howard University College of Medicine, 2041 Georgia Avenue, N.W., Washington, DC, 20060, USA
- Department of Pathology, Howard University College of Medicine, Washington, DC, USA
| | - Edward Lee
- Department of Pathology, Howard University College of Medicine, Washington, DC, USA
| | - Babak Shokrani
- Department of Pathology, Howard University College of Medicine, Washington, DC, USA
| | - Tina Boortalary
- Department of Medicine and Cancer Research Center, Howard University College of Medicine, 2041 Georgia Avenue, N.W., Washington, DC, 20060, USA
| | - Zaki A Sherif
- Department of Medicine and Cancer Research Center, Howard University College of Medicine, 2041 Georgia Avenue, N.W., Washington, DC, 20060, USA
- Department of Biochemistry and Molecular Biology, Howard University College of Medicine, Washington, DC, USA
| | - Mehdi Nouraie
- Department of Medicine and Vascular Institute Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA
| | - Adeyinka O Laiyemo
- Department of Medicine and Cancer Research Center, Howard University College of Medicine, 2041 Georgia Avenue, N.W., Washington, DC, 20060, USA
| | - Kawtar Alkhalloufi
- Department of Medicine and Cancer Research Center, Howard University College of Medicine, 2041 Georgia Avenue, N.W., Washington, DC, 20060, USA
| | - Hassan Brim
- Department of Medicine and Cancer Research Center, Howard University College of Medicine, 2041 Georgia Avenue, N.W., Washington, DC, 20060, USA
- Department of Pathology, Howard University College of Medicine, Washington, DC, USA
| | - Hassan Ashktorab
- Department of Medicine and Cancer Research Center, Howard University College of Medicine, 2041 Georgia Avenue, N.W., Washington, DC, 20060, USA.
| |
Collapse
|
|
22
|
Xu L, Lu W, Li P, Shen F, Mi YQ, Fan JG. A comparison of hepatic steatosis index, controlled attenuation parameter and ultrasound as noninvasive diagnostic tools for steatosis in chronic hepatitis B. Dig Liver Dis 2017; 49:910-917. [PMID: 28433586 DOI: 10.1016/j.dld.2017.03.013] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 03/18/2017] [Accepted: 03/21/2017] [Indexed: 12/11/2022]
Abstract
AIMS To evaluate the value of noninvasive tools for diagnosis of hepatic steatosis in patients with chronic hepatitis B (CHB). METHODS Consecutive treatment-naïve patients with CHB with body mass index less than 30kg/m2 who underwent liver biopsy, ultrasound and FibroScan® were enrolled. The diagnostic performance of controlled attenuation parameter (CAP), hepatic steatosis index (HSI) and ultrasound for hepatic steatosis compared with liver biopsy was assessed. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy, with comparisons using the DeLong test. RESULTS CAP and HSI accuracies were significantly higher than that of ultrasound to detect patients with biopsy-proven mild steatosis (S1, 65.3%, 56.5%, respectively, vs. 17.7%, χ2=46.305, 31.736, both P<0.05)and moderate-severe (S2-3) steatosis (92.3%, 100%, respectively, vs. 53.8%, χ2=4.887, 7.800, P=0.037, 0.007, respectively). Both CAP and HSI had lower underestimation rates of steatosis grade than ultrasound (12%, 14.8%, respectively, vs. 29.5%, χ2=9.765, 6.452; P<0.05 for both), but they exhibited higher overestimation rates (30.5%, 38.2%, respectively, vs. 12.4%, χ2=39.222, 70.986; both P<0.05). The AUROCs of CAP and HSI were 0.780 (95% confidence intervals [CIs] 0.735-0.822) and 0.655 (95%CI 0.604-0.704) for S ≥1, 0.932 (95%CI 0.902-0.956) and 0.755 (95%CI 0.707-0.799) for S ≥2, 0.990 (95%CI 0.974-0.998) and 0.786 (95% CI 0.740-0.827) for S3, respectively. CONCLUSION CAP might be more accurate for detecting hepatic steatosis than HSI and ultrasound in patients with CHB, but further studies are needed to reduce the overestimation rates.
Collapse
Affiliation(s)
- Liang Xu
- First Center for Clinical College, Tianjin Medical University, Tianjin, China; Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China; Tianjin Research Institute of Liver Diseases, Tianjin, China
| | - Wei Lu
- First Center for Clinical College, Tianjin Medical University, Tianjin, China; Tianjin First Center Hospital, Tianjin, China; Tianjin Research Institute of Liver Diseases, Tianjin, China.
| | - Ping Li
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China; Tianjin Research Institute of Liver Diseases, Tianjin, China
| | - Feng Shen
- Department of Gastroenterology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yu-Qiang Mi
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China; Tianjin Research Institute of Liver Diseases, Tianjin, China.
| | - Jian-Gao Fan
- Department of Gastroenterology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
| |
Collapse
|
|
23
|
Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Lédinghen V, Kumar M, Lupsor-Platon M, Han KH, Cardoso AC, Ferraioli G, Chan WK, Wong VWS, Myers RP, Chayama K, Friedrich-Rust M, Beaugrand M, Shen F, Hiriart JB, Sarin SK, Badea R, Jung KS, Marcellin P, Filice C, Mahadeva S, Wong GLH, Crotty P, Masaki K, Bojunga J, Bedossa P, Keim V, Wiegand J. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol 2017; 66:1022-1030. [PMID: 28039099 DOI: 10.1016/j.jhep.2016.12.022] [Citation(s) in RCA: 805] [Impact Index Per Article: 100.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Revised: 12/13/2016] [Accepted: 12/21/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis. METHODS A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan®) for grading of steatosis (S0-S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades. RESULTS Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5-17) for NAFLD/NASH patients, 10 (3.5-16) for diabetics and 4.4 (3.8-5.0) per BMI unit. Areas under the curves were 0.823 (0.809-0.837) and 0.865 (0.850-0.880) respectively. Optimal cut-offs were 248 (237-261) and 268 (257-284) for those above S0 and S1 respectively. CONCLUSIONS CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes. LAY SUMMARY There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238.
Collapse
Affiliation(s)
- Thomas Karlas
- Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - David Petroff
- Clinical Trial Centre, University of Leipzig, Leipzig, Germany; IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany
| | | | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, XinHua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu-Qiang Mi
- Research Institute of Liver Diseases, Tianjin Second People's Hospital, Tianjin, China
| | - Victor de Lédinghen
- Centre d'Investigation de la Fibrose hépatique, Hôpital Haut-Lévêque, Centre Hospitalo-Universitaire de Bordeaux, Pessac, France
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Monica Lupsor-Platon
- Department of Medical Imaging, Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Cluj-Napoca, Romania
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ana C Cardoso
- Department of Hepatology and INSERM U773-CRB3, Hôpital Beaujon, APHP, University of Paris 7, Clichy, France
| | - Giovanna Ferraioli
- Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Medical School University of Pavia, Pavia, Italy
| | - Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Gastrointestinal Endoscopy Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Robert P Myers
- Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Kazuaki Chayama
- Departments of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan
| | - Mireen Friedrich-Rust
- Department of Internal Medicine, J.W. Goethe-University Hospital, Frankfurt, Germany
| | | | - Feng Shen
- Center for Fatty Liver, Department of Gastroenterology, XinHua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jean-Baptiste Hiriart
- Centre d'Investigation de la Fibrose hépatique, Hôpital Haut-Lévêque, Centre Hospitalo-Universitaire de Bordeaux, Pessac, France
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Radu Badea
- Department of Medical Imaging, Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Cluj-Napoca, Romania
| | - Kyu Sik Jung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Patrick Marcellin
- Department of Hepatology and INSERM U773-CRB3, Hôpital Beaujon, APHP, University of Paris 7, Clichy, France
| | - Carlo Filice
- Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Medical School University of Pavia, Pavia, Italy
| | - Sanjiv Mahadeva
- Gastroenterology and Hepatology Unit, Gastrointestinal Endoscopy Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Pam Crotty
- Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Keiichi Masaki
- Departments of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan
| | - Joerg Bojunga
- Department of Internal Medicine, J.W. Goethe-University Hospital, Frankfurt, Germany
| | - Pierre Bedossa
- Department of Pathology, Physiology and Imaging, University Paris Diderot, Paris, France
| | - Volker Keim
- Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Johannes Wiegand
- Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany.
| |
Collapse
|
|
24
|
Ongoing liver inflammation in patients with chronic hepatitis C and sustained virological response. PLoS One 2017; 12:e0171755. [PMID: 28196130 PMCID: PMC5308806 DOI: 10.1371/journal.pone.0171755] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Accepted: 01/25/2017] [Indexed: 12/19/2022] Open
Abstract
Background Novel direct-acting antiviral DAA combination therapies tremendously improved sustained virologic response (SVR) rates in patients with chronic HCV infection. SVR is typically accompanied by normalization of liver enzymes, however, hepatic inflammation, i.e. persistently elevated aminotransferase levels may persist despite HCV eradication. Aim: To investigate prevalence and risk factors for ongoing hepatic inflammation after SVR in two large patient cohorts. Methods This post-hoc analysis was based on prospectively collected demographic and clinical data from 834 patients with SVR after HCV treatment with either PegIFN- or DAA-based treatment regimens from the PRAMA trial (n = 341) or patients treated at our outpatient clinic (n = 493). Results We observed an unexpected high prevalence of post-SVR inflammation, including patients who received novel IFN-free DAA-based therapies. Up to 10% of patients had ongoing elevation of aminotransferase levels and another 25% showed aminotransferase activity above the so-called healthy range. Several baseline factors were independently associated with post-SVR aminotransferase elevation. Among those, particularly male gender, advanced liver disease and markers for liver steatosis were strongly predictive for persistent ALT elevation. The use of IFN-based antiviral treatment was independently correlated with post-SVR inflammation, further supporting the overall benefit of IFN-free combination regimens. Conclusion This is the first comprehensive study on a large patient cohort investigating the prevalence and risk factors for ongoing liver inflammation after eradication of HCV. Our data show a high proportion of patients with ongoing hepatic inflammation despite HCV eradication with potential implications for the management of approximately one third of all patients upon SVR.
Collapse
|
|
25
|
Nonalcoholic fatty liver disease in Asia: emerging perspectives. J Gastroenterol 2017; 52:164-174. [PMID: 27637587 DOI: 10.1007/s00535-016-1264-3] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Accepted: 09/06/2016] [Indexed: 02/07/2023]
Abstract
As in the West, nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease in Asia, with a prevalence higher than 40 % in some countries. The risk factors for NAFLD development are similar to those in Western countries, including increased body mass index, diabetes, insulin resistance, and metabolic syndrome. NAFLD in Asians is associated with different extrahepatic manifestations involving the cardiovascular, gastrointestinal, and renal systems. A considerable proportion of Asians with NAFLD are described as having "lean" NAFLD. Present in approximately 20 % of the Asian population, lean NAFLD is closely linked with insulin resistance, diabetes, and other metabolic complications, but its association with disease progression to nonalcoholic steatohepatitis and cirrhosis remains to be defined. There is emerging evidence of the interactions of NAFLD with hepatitis B virus and hepatitis C virus infection in Asia. Unlike in Western countries, NAFLD constitutes only a minority of cirrhosis and hepatocellular carcinoma cases in Asia. Possible explanations are the lower prevalence of obesity and the overwhelming problem of viral hepatitis in Asia. With aging of the obesity cohort in Asia, NAFLD-related liver complications are expected to increase.
Collapse
|
|
26
|
Down C, Mehta N, Marks K. The Risk of Cardiovascular Disease, Diabetes, Liver-Related Outcomes, and Death Over 10 Years in HIV/HCV-Coinfected Patients With and Without Steatosis. AIDS Res Hum Retroviruses 2016; 32:868-71. [PMID: 27206965 DOI: 10.1089/aid.2016.0051] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Coinfection with HIV/HCV is associated with more severe liver disease, including increased frequency of steatosis and significant fibrosis, compared to patients mono-infected with HCV or HIV. We sought to explore the impact of steatosis on cardiovascular disease (CVD), liver-related outcomes, and survival. METHODS An IRB-approved, single-center retrospective cohort study was undertaken to analyze 10-year clinical outcomes in HIV/HCV-coinfected patients. Liver biopsy was performed at study entry for the evaluation of HCV disease; a study pathologist graded samples for fibrosis and steatosis. Clinical outcomes, including cardiac events, liver function with FIB-4, AST to Platelet Ratio Index, and survival were assessed over 10 years. RESULTS At cohort entry N = 105, mean age 45 ± 7 years, 70% male, and 56% had steatosis present on biopsy. During the 10-year follow-up, no association was found between incident CVD, changes in noninvasive liver fibrosis measures, or survival in the steatosis group compared to nonsteatosis group. However, nonsignificant trends were noted. Overall, mortality for this coinfected population was 25% over 10 years, with liver disease as the most common cause of death. CONCLUSIONS Given the prevalence of steatosis in approximately half of coinfected patients, larger studies are warranted to determine if steatosis is associated with cardiac disease, diabetes, or liver disease progression in this population. Furthermore, 10-year mortality for this population was very high, underscoring the importance of HCV treatment and need for a better understanding of other variables responsible for decreased survival in this population.
Collapse
Affiliation(s)
- Carrie Down
- New York Presbyterian Hospital, Weill Cornell, New York, New York
| | | | - Kristen Marks
- New York Presbyterian Hospital, Weill Cornell, Infectious Disease, New York, New York
| |
Collapse
|
|
27
|
Galal SM, Abdel Aal FH, Mohammed AED, Mohamed MZ, Abd El-Rahman YG. Chronic viral hepatitis C in pediatric age group; assessment of viral activity and hepatic fibrosis by 1H magnetic resonance spectroscopy and diffusion weighted imaging in asymptomatic patient. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2016. [DOI: 10.1016/j.ejrnm.2016.05.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
|
|
28
|
Aguilar M, Liu B, Holt EW, Bhuket T, Wong RJ. Impact of obesity and diabetes on waitlist survival, probability of liver transplantation and post-transplant survival among chronic hepatitis C virus patients. Liver Int 2016; 36:1167-75. [PMID: 26858016 DOI: 10.1111/liv.13091] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2015] [Accepted: 02/02/2016] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS The rising prevalence of obesity and diabetes mellitus (DM) among hepatitis C virus (HCV) patients contributes to concurrent nonalcoholic fatty liver disease (NAFLD). We aim to evaluate the impact of concurrent obesity or DM on waitlist survival and probability of liver transplantation (LT) among adults with chronic HCV awaiting LT. METHODS Using 2003-2013 United Network for Organ Sharing data, we evaluated the impact of obesity and DM among adults with chronic HCV awaiting LT: non-obese, non-DM vs. obese, non-DM (obese) vs. non-obese, DM (DM) vs. obese and DM. Overall, LT waitlist survival and probability of receiving LT were evaluated using Kaplan-Meier and multivariate logistic regression models. RESULTS From 2003-2013, there were 43 478 new LT waitlist registrants with chronic HCV (21.0% with HCC, 79% without HCC). Obesity was associated with lower probability of receiving LT (OR, 0.91; 95% CI, 0.85-0.97; P < 0.01), and lower probability of waitlist mortality (OR, 0.80; 95% CI, 0.72-0.89; P < 0.001) when compared to non-obese patients. DM among HCV patients did not impact probability of waitlist survival or receiving LT. When evaluating post-LT survival, compared to non-obese, non-DM patients, obese HCV patients had significantly lower post-LT mortality (HR 0.86; 95%CI, 0.81-0.92; P < 0.001); whereas, HCV patients with DM had significantly higher post-LT mortality (HR, 1.22; 95% CI, 1.12-1.33; P < 0.001). CONCLUSION Among adults with chronic HCV awaiting LT in the US, obesity is associated with lower probability of receiving LT, but did not impact waitlist survival. DM among chronic HCV patients did not impact waitlist survival or probability of LT.
Collapse
Affiliation(s)
- Maria Aguilar
- Department of Medicine, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - Benny Liu
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - Edward W Holt
- Department of Transplantation, Division of Hepatology, California Pacific Medical Center, San Francisco, CA, USA
| | - Taft Bhuket
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| |
Collapse
|
|
29
|
Cardoso AC, Beaugrand M, de Ledinghen V, Douvin C, Poupon R, Trinchet JC, Ziol M, Bedossa P, Marcellin P. Diagnostic performance of controlled attenuation parameter for predicting steatosis grade in chronic hepatitis B. Ann Hepatol 2016; 14:826-36. [PMID: 26436354 DOI: 10.5604/16652681.1171762] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND & AIMS A novel controlled attenuation parameter (CAP) using the signals acquired by the FibroScan® has been developed as a method for evaluating steatosis. The aim of this study is to assess the performance of the CAP for the detection and quantification of steatosis in patients with chronic hepatitis B (CHB). MATERIAL AND METHODS 136 subjects with CHB underwent liver biopsy and FibroScan® within 60 days. CAP was evaluated retrospectively using raw FibroScan® data. Steatosis was graded as follows: S0 (steatosis < 10% of hepatocytes), S1 (10 to < 30%), S2 (30 to < 60%) or S3 (≥ 60%). Performance was evaluated by area under the receiver operating characteristic (AUROC) curve. RESULTS Proportions of each steatosis grade (S0-S3) were 78, 10, 9 and 3%, respectively. Using univariate analysis, liver stiffness measurement (LMS) significantly correlated with fibrosis (τ = 0.43; P < 10-10), sex, necro-inflammatory activity, steatosis, age, NASH, and perisinusoidal fibrosis, and with liver fibrosis (P < 10-8) and perisinusoidal fibrosis (P = 0.008) using multivariate analysis. CAP correlated with steatosis (τ = 0.38, P < 10-7), body mass index, NASH, fibrosis and perisinusoidal fibrosis using univariate analysis, but only steatosis (P < 10-10) and perisinusoidal fibrosis (P = 0.002) using multivariate analysis. AUROCs for LSM were: 0.77 (0.69-0.85), 0.87 (0.80-0.95), and 0.93 (0.83-1.00), respectively, for fibrosis stages F ≥ 2, F ≥ 3 and F = 4. AUROCs for CAP were: 0.82 (0.73-0.92), 0.82 (0.69-0.95), and 0.97 (0.84-1.00) for ≥ S1, ≥ S2 and S3 steatosis, respectively. CONCLUSIONS In conclusión CAP is a novel, accurate non-invasive tool and may be suitable for detecting and quantifying steatosis in CHB patients.
Collapse
Affiliation(s)
- Ana C Cardoso
- Department of Hepatology and INSERM U773-CRB3, Hôpital Beaujon, APHP, University of Paris 7, Clichy, France
| | | | - Victor de Ledinghen
- Department of Hepatology, Hôpital Haut-Leveque, CHU Bordeaux Pessac, France and INSERM U1053, Université Bordeaux Segalen, Bordeaux, France
| | | | - Raoul Poupon
- Department of Hepatology, Hôpital Saint Antoine, Paris, France
| | | | - Marianne Ziol
- Department of Anatomy and Pathology, Hospital Group Paris-Seine-Saint Denis, Hôpital Jean Verdier, AP-PH, Bondy, France and Paris 13 University, Sorbonne Paris Cité, UFR SMBH, Bobigny, France
| | - Pierre Bedossa
- Department of Anatomy Pathology and INSERM U773-CRB3, Hôpital Beaujon, Clichy, France
| | - Patrick Marcellin
- Department of Hepatology and INSERM U773-CRB3, Hôpital Beaujon, APHP, University of Paris 7, Clichy, France
| |
Collapse
|
|
30
|
Adinolfi LE, Rinaldi L, Guerrera B, Restivo L, Marrone A, Giordano M, Zampino R. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations. Int J Mol Sci 2016; 17:ijms17060803. [PMID: 27231906 PMCID: PMC4926337 DOI: 10.3390/ijms17060803] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 05/15/2016] [Accepted: 05/19/2016] [Indexed: 02/06/2023] Open
Abstract
The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV)-associated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases.
Collapse
Affiliation(s)
- Luigi Elio Adinolfi
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Luca Rinaldi
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Barbara Guerrera
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Luciano Restivo
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Aldo Marrone
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Mauro Giordano
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Rosa Zampino
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| |
Collapse
|
|
31
|
Kralj D, Jukić LV, Stojsavljević S, Duvnjak M, Smolić M, Čurčić IB. Hepatitis C Virus, Insulin Resistance, and Steatosis. J Clin Transl Hepatol 2016; 4:66-75. [PMID: 27047774 PMCID: PMC4807145 DOI: 10.14218/jcth.2015.00051] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Revised: 02/15/2016] [Accepted: 02/16/2016] [Indexed: 12/15/2022] Open
Abstract
Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide. Liver steatosis is a common finding in many hepatic and extrahepatic disorders, the most common being metabolic syndrome (MS). Over time, it has been shown that the frequent coexistence of these two conditions is not coincidental, since many epidemiological, clinical, and experimental studies have indicated HCV to be strongly associated with liver steatosis and numerous metabolic derangements. Here, we present an overview of publications that provide clinical evidence of the metabolic effects of HCV and summarize the available data on the pathogenetic mechanisms of this association. It has been shown that HCV infection can induce insulin resistance (IR) in the liver and peripheral tissues through multiple mechanisms. Substantial research has suggested that HCV interferes with insulin signaling both directly and indirectly, inducing the production of several proinflammatory cytokines. HCV replication, assembly, and release from hepatocytes require close interactions with lipid droplets and host lipoproteins. This modulation of lipid metabolism in host cells can induce hepatic steatosis, which is more pronounced in patients with HCV genotype 3. The risk of steatosis depends on several viral factors (including genotype, viral load, and gene mutations) and host features (visceral obesity, type 2 diabetes mellitus, genetic predisposition, medication use, and alcohol consumption). HCV-related IR and steatosis have been shown to have a remarkable clinical impact on the prognosis of HCV infection and quality of life, due to their association with resistance to antiviral therapy, progression of hepatic fibrosis, and development of hepatocellular carcinoma. Finally, HCV-induced IR, oxidative stress, and changes in lipid and iron metabolism lead to glucose intolerance, arterial hypertension, hyperuricemia, and atherosclerosis, resulting in increased cardiovascular mortality.
Collapse
Affiliation(s)
- Dominik Kralj
- Department of Gastroenterology and Hepatology, Sisters of Charity University Hospital Center, Zagreb, Croatia
| | - Lucija Virović Jukić
- Department of Gastroenterology and Hepatology, Sisters of Charity University Hospital Center, Zagreb, Croatia
| | - Sanja Stojsavljević
- Department of Gastroenterology and Hepatology, Sisters of Charity University Hospital Center, Zagreb, Croatia
| | - Marko Duvnjak
- Department of Gastroenterology and Hepatology, Sisters of Charity University Hospital Center, Zagreb, Croatia
| | - Martina Smolić
- Department of Pharmacology, Faculty of Medicine, University of Osijek, Osijek, Croatia
| | - Ines Bilić Čurčić
- Department of Pharmacology, Faculty of Medicine, University of Osijek, Department of Endocrinology and metabolism disorders, University Hospital Center, Osijek, Osijek, Croatia
| |
Collapse
|
|
32
|
Petta S, Valenti L, Bugianesi E, Targher G, Bellentani S, Bonino F. A "systems medicine" approach to the study of non-alcoholic fatty liver disease. Dig Liver Dis 2016; 48:333-342. [PMID: 26698409 DOI: 10.1016/j.dld.2015.10.027] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2015] [Revised: 10/18/2015] [Accepted: 10/31/2015] [Indexed: 02/07/2023]
Abstract
The prevalence of fatty liver (steatosis) in the general population is rapidly increasing worldwide. The progress of knowledge in the physiopathology of fatty liver is based on the systems biology approach to studying the complex interactions among different physiological systems. Similarly, translational and clinical research should address the complex interplay between these systems impacting on fatty liver. The clinical needs drive the applications of systems medicine to re-define clinical phenotypes, assessing the multiple nature of disease susceptibility and progression (e.g. the definition of risk, prognosis, diagnosis criteria, and new endpoints of clinical trials). Based on this premise and in light of recent findings, the complex mechanisms involved in the pathology of fatty liver and their impact on the short- and long-term clinical outcomes of cardiovascular, metabolic liver diseases associated with steatosis are presented in this review using a new "systems medicine" approach. A new data set is proposed for studying the impairments of different physiological systems that have an impact on fatty liver in different subsets of subjects and patients.
Collapse
Affiliation(s)
- Salvatore Petta
- Section of Gastroenterology, Di.Bi.M.I.S Policlinico Paolo Giaccone Hospital, University of Palermo, Italy
| | - Luca Valenti
- Internal Medicine, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, University of Milan, Italy
| | - Elisabetta Bugianesi
- Gastroenterology and Hepatology, Department of Medical Sciences, Città della Salute e della Scienza di Torino Hospital, University of Turin, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University Hospital of Verona, Italy
| | - Stefano Bellentani
- Shrewsbury and Telford NHS Trust, Department of Gastroenterology, Shrewsbury, UK; Fondazione Italiana Fegato, Bassovizza, Trieste, Italy
| | - Ferruccio Bonino
- General Medicine 2, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Italy.
| |
Collapse
|
|
33
|
Poortahmasebi V, Emami Aleagha MS, Amiri M, Qorbani M, Farahmand M, Asayesh H, Alavian SM. Prevalence of hepatic steatosis and associated factors in Iranian patients with chronic hepatitis C. Med J Islam Repub Iran 2016; 30:322. [PMID: 27390692 PMCID: PMC4898852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2014] [Accepted: 07/04/2015] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Hepatic steatosis is commonly observed in patients with chronic hepatitis C (CHC). Many studies indicate a relationship between steatosis and fibrosis progression. The aim of this study was to analyze the prevalence of hepatic steatosis and related factors in Iranian CHC patients. METHODS One hundred and fifteen consecutive patients with CHC were enrolled which were treatment- naïve. The patients were divided into groups with and without steatosis according to the result of liver biopsy (58.3% and 41.7%, respectively). Demographic, histological, biochemical and virological factors were examined and compared in all patients. RESULTS In terms of host factors, body mass index (BMI), triglyceride, fasting blood glucose (FBG), necroinflammatory activity and severity in fibrosis of CHC patients with steatosis was significantly higher than the patients without steatosis. Of viral factors, HCV viral load was not significantly altered in patients with steatosis. Moreover, HCV genotypes did not meet such association. Using multivariate regression analysis, parameters of BMI values, FBG level and stage of fibrosis were independently associated with steatosis. CONCLUSION Our data indicate that CHC patients are more susceptible to development of hepatic steatosis. Based on our results, grade of steatosis appears to be associated with hepatic fibrosis progression rate in CHC patients.
Collapse
Affiliation(s)
- Vahdat Poortahmasebi
- 1 PhD Candidate, Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mohammad Sajad Emami Aleagha
- 2 PhD Candidate, Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Mehdi Amiri
- 3 Research Assistant, Department of Cell Biology and Anatomy, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
| | - Mostafa Qorbani
- 4 Assistant Professor, Department of Community Medicine, Alborz University of Medical Sciences, Karaj, Iran & Non-Communicable Disease Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mohammad Farahmand
- 5 MSc, Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
| | - Hamid Asayesh
- 6 Instructor, Department of Medical Emergencies, Qom University of Medical Sciences, Qom, Iran. .
| | - Seyed Moayed Alavian
- 7 Professor of Gastroenterology and Hepatology, Middle East Liver Diseases (MELD) Center, Tehran, Iran. ,(Corresponding author) Professor of Gastroenterology and Hepatology, Middle East Liver Diseases (MELD) Center, Tehran, Iran.
| |
Collapse
|
|
34
|
Wu JY, Tuomi A, Beland MD, Konrad J, Glidden D, Grand D, Merck D. Quantitative analysis of ultrasound images for computer-aided diagnosis. J Med Imaging (Bellingham) 2016; 3:014501. [PMID: 26835502 DOI: 10.1117/1.jmi.3.1.014501] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Accepted: 12/18/2015] [Indexed: 01/06/2023] Open
Abstract
We propose an adaptable framework for analyzing ultrasound (US) images quantitatively to provide computer-aided diagnosis using machine learning. Our preliminary clinical targets are hepatic steatosis, adenomyosis, and craniosynostosis. For steatosis and adenomyosis, we collected US studies from 288 and 88 patients, respectively, as well as their biopsy or magnetic resonanceconfirmed diagnosis. Radiologists identified a region of interest (ROI) on each image. We filtered the US images for various texture responses and use the pixel intensity distribution within each ROI as feature parameterizations. Our craniosynostosis dataset consisted of 22 CT-confirmed cases and 22 age-matched controls. One physician manually measured the vectors from the center of the skull to the outer cortex at every 10 deg for each image and we used the principal directions as shape features for parameterization. These parameters and the known diagnosis were used to train classifiers. Testing with cross-validation, we obtained 72.74% accuracy and 0.71 area under receiver operating characteristics curve for steatosis ([Formula: see text]), 77.27% and 0.77 for adenomyosis ([Formula: see text]), and 88.63% and 0.89 for craniosynostosis ([Formula: see text]). Our framework is able to detect a variety of diseases with high accuracy. We hope to include it as a routinely available support system in the clinic.
Collapse
Affiliation(s)
- Jie Ying Wu
- Brown University , School of Engineering, 82 Hope Street, Providence, Rhode Island 02912, United States
| | - Adam Tuomi
- Brown University , Alpert Medical School, 222 Richmond Street, Providence, Rhode Island 02903, United States
| | - Michael D Beland
- Rhode Island Hospital , Department of Diagnostic Imaging, 593 Eddy Street, Providence, Rhode Island 02903, United States
| | - Joseph Konrad
- Rhode Island Hospital , Department of Diagnostic Imaging, 593 Eddy Street, Providence, Rhode Island 02903, United States
| | - David Glidden
- Brown University , Alpert Medical School, 222 Richmond Street, Providence, Rhode Island 02903, United States
| | - David Grand
- Rhode Island Hospital , Department of Diagnostic Imaging, 593 Eddy Street, Providence, Rhode Island 02903, United States
| | - Derek Merck
- Rhode Island Hospital , Department of Diagnostic Imaging, 593 Eddy Street, Providence, Rhode Island 02903, United States
| |
Collapse
|
|
35
|
Pavlides M, Banerjee R, Sellwood J, Kelly CJ, Robson MD, Booth JC, Collier J, Neubauer S, Barnes E. Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. J Hepatol 2016; 64:308-315. [PMID: 26471505 PMCID: PMC4751288 DOI: 10.1016/j.jhep.2015.10.009] [Citation(s) in RCA: 159] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 09/22/2015] [Accepted: 10/07/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Multiparametric magnetic resonance (MR) imaging has been demonstrated to quantify hepatic fibrosis, iron, and steatosis. The aim of this study was to determine if MR can be used to predict negative clinical outcomes in liver disease patients. METHODS Patients with chronic liver disease (n=112) were recruited for MR imaging and data on the development of liver related clinical events were collected by medical records review. The median follow-up was 27months. MR data were analysed blinded for the Liver Inflammation and Fibrosis score (LIF; <1, 1-1.99, 2-2.99, and ⩾3 representing normal, mild, moderate, and severe liver disease, respectively), T2∗ for liver iron content and proportion of liver fat. Baseline liver biopsy was performed in 102 patients. RESULTS Liver disease aetiologies included non-alcoholic fatty liver disease (35%) and chronic viral hepatitis (30%). Histologically, fibrosis was mild in 54 (48%), moderate in 17 (15%), and severe in 31 (28%) patients. Overall mortality was 5%. Ten patients (11%) developed at least one liver related clinical event. The negative predictive value of LIF<2 was 100%. Two patients with LIF 2-2.99 and eight with LIF⩾3 had a clinical event. Patients with LIF⩾3 had a higher cumulative risk for developing clinical events, compared to those with LIF<1 (p=0.02) and LIF 1-1.99 (p=0.03). Cox regression analysis including all 3 variables (fat, iron, LIF) resulted in an enhanced LIF predictive value. CONCLUSIONS Non-invasive standardised multiparametric MR technology may be used to predict clinical outcomes in patients with chronic liver disease.
Collapse
Affiliation(s)
- Michael Pavlides
- Translational Gastroenterology Unit, University of Oxford, UK,Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK
| | | | - Joanne Sellwood
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK
| | | | - Matthew D. Robson
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK
| | | | - Jane Collier
- Translational Gastroenterology Unit, University of Oxford, UK
| | - Stefan Neubauer
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK
| | - Eleanor Barnes
- Translational Gastroenterology Unit, University of Oxford, UK; Peter Medawar Building, University of Oxford, Oxford, UK.
| |
Collapse
|
|
36
|
Wang Y, Hou JL. Fibrosis assessment: impact on current management of chronic liver disease and application of quantitative invasive tools. Hepatol Int 2016; 10:448-61. [DOI: 10.1007/s12072-015-9695-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 12/07/2015] [Indexed: 12/15/2022]
|
|
37
|
Dyal HK, Aguilar M, Bhuket T, Liu B, Holt EW, Torres S, Cheung R, Wong RJ. Concurrent Obesity, Diabetes, and Steatosis Increase Risk of Advanced Fibrosis Among HCV Patients: A Systematic Review. Dig Dis Sci 2015; 60:2813-24. [PMID: 26138651 DOI: 10.1007/s10620-015-3760-3] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 06/10/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Rising rates of obesity, diabetes mellitus (DM), and nonalcoholic fatty liver disease among patients with chronic hepatitis C virus infection (HCV) may contribute to more rapid disease progression. AIM To evaluate the impact of concurrent obesity, DM, and steatosis on disease progression among HCV patients. METHODS A systematic review using structured keyword search of MEDLINE and EMBASE from January 1, 2001, to July 1, 2014, was performed to identify original articles evaluating the association of obesity, DM, and steatosis with advanced fibrosis (AF) among adults with chronic HCV. Studies involving HCV patients coinfected with human immunodeficiency virus, hepatitis B virus, hepatocellular carcinoma, or other chronic liver diseases were excluded. Quality assessment utilized Newcastle-Ottawa Scale. RESULTS Twenty cohort studies met inclusion criteria for analyses. Obesity was associated with increased risk of AF in seven studies with effect size ranging from OR 1.08 to 7.69. However, four studies did not demonstrate a significant association between obesity and AF. The presence of advanced steatosis among HCV patients was associated with increased risk of AF in 12 studies (OR 1.80-14.3). Concurrent DM was associated with increased risk of AF in six studies (OR 2.25-9.24). Thirteen studies were good quality, and seven studies were fair quality. CONCLUSION Concurrent DM and steatosis are associated with increased risk of AF among chronic HCV patients. The majority of studies demonstrated significant associations of obesity with AF. Targeted interventions to optimize management of obesity-related diseases among HCV patients may help mitigate HCV disease progression.
Collapse
Affiliation(s)
- Harleen K Dyal
- Division of Gastroenterology and Hepatology, Highland Hospital, Alameda Health System - Highland Hospital Campus, Highland Care Pavilion 5th Floor, Endoscopy Unit, 1411 East 31st Street, Oakland, CA, 94602, USA,
| | | | | | | | | | | | | | | |
Collapse
|
|
38
|
Abstract
There has long been evidence that hepatitis C can lead to persistent infection in a high proportion of infected individuals, and can progress to chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). The transition from acute to chronic hepatitis C is usually sub-clinical. Accurate studies of the time course for clearance of acute hepatitis C are difficult to carry out because of the silent onset of the acute disease. The likelihood of spontaneous HCV resolution is associated with several genetic factors, including IL28B inheritance and the DQB1*0301 allele of the major histocompatibility complex class II. Most data suggest that resolution in the acute phase without progression to chronic disease is not accompanied by significant disease, but minor histological lesions have been observed in anti-HCV positive, HCV RNA negative individuals. The risk of reinfection remains a possibility after clearance of acute hepatitis C. High rates of sexually-transmitted infection are being reported in HIV positive men who have sex with men (MSM). Chronic infection with HCV is the leading cause of end-stage liver disease, hepatocellular carcinoma (HCC) and liver related death in the Western world. The natural history of the chronic disease remains incompletely defined. It is generally a slowly progressive disease characterized by persistent hepatic inflammation, leading to the development of cirrhosis in approximately 10-20% of patients over 20-30 years of HCV infection. However, the published data indicate varying progression rates to cirrhosis. Overall, once cirrhosis has developed there is a 1-5% annual risk of HCC and a 3-6% annual risk of hepatic decompensation. Following an episode of decompensation the risk of death in the following year is between 15% and 20%. The high number of chronically infected individuals, the burden of disease, and the absence of a vaccine indicates that treatment will form part of the disease control but the impact, effectiveness and outcomes of treatment in various groups remain uncertain. Several studies and meta-analysis have concluded that eradication of HCV with antiviral therapy reduces the risk of HCC in patients with chronic hepatitis C, independent of fibrosis stage, but the risk is not eliminated.
Collapse
|
|
39
|
Konerman MA, Yapali S, Lok AS. Systematic review: identifying patients with chronic hepatitis C in need of early treatment and intensive monitoring--predictors and predictive models of disease progression. Aliment Pharmacol Ther 2014; 40:863-79. [PMID: 25164152 PMCID: PMC4167918 DOI: 10.1111/apt.12921] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2014] [Revised: 07/07/2014] [Accepted: 07/26/2014] [Indexed: 12/15/2022]
Abstract
BACKGROUND Advances in hepatitis C therapies have led to increasing numbers of patients seeking treatment. As a result, logistical and financial concerns regarding how treatment can be provided to all patients with chronic hepatitis C (CHC) have emerged. AIM To evaluate predictors and predictive models of histological progression and clinical outcomes for patients with CHC. METHODS MEDLINE via PubMed, EMBASE, Web of Science and Scopus were searched for studies published between January 2003 and June 2014. Two authors independently reviewed articles to select eligible studies and performed data abstraction. RESULTS Twenty-nine studies representing 5817 patients from 20 unique cohorts were included. The outcome incidence rates were widely variable: 16-61% during median follow-up of 2.5-10 years for fibrosis progression; 13-40% over 2.3-14.4 years for hepatic decompensation and 8-47% over 3.9-14.4 years for overall mortality. Multivariate analyses showed that baseline steatosis and baseline fibrosis score were the most consistent predictors of fibrosis progression (significant in 6/21 and 5/21, studies, respectively) while baseline platelet count (significant in 6/13 studies), aspartate and alanine aminotransferase (AST/ALT) ratio, albumin, bilirubin and age (each significant in 4/13 studies) were the most consistent predictors of clinical outcomes. Five studies developed predictive models but none were externally validated. CONCLUSIONS Our review identified the variables that most consistently predict outcomes of patients with chronic hepatitis C allowing the application of risk based approaches to identify patients in need of early treatment and intensive monitoring. This approach maximises effective use of resources and costly new direct-acting anti-viral agents.
Collapse
Affiliation(s)
- M A Konerman
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA
| | | | | |
Collapse
|
|
40
|
Jafarian A, Ebrahimi A, Azmoudeh Ardalan F, Dashti H, Rahimi M, Salehi M, Nasiri Toosi M. NAFLD Prevalence in a Young Cadaveric Organ Donor Population. HEPATITIS MONTHLY 2014; 14:e21574. [PMID: 25419218 PMCID: PMC4238153 DOI: 10.5812/hepatmon.21574] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2014] [Revised: 09/04/2014] [Accepted: 09/11/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Liver transplantation is a critical survival point for patients with end stage liver diseases. It can dramatically increase patients' survival if the donor liver is intact. One aspect of liver health is absence of steatosis. Nonalcoholic Steato Hepatitis (NASH) and Nonalcoholic Fatty Liver Disease (NAFLD) are increasing among young adults and patients living with chronic liver diseases. OBJECTIVES In this study, we determined the prevalence of NALFD in livers of brain-dead donors in Imam-Khomeini hospital Complex, Tehran, Iran. We assumed that the calculated prevalence would represent NAFLD prevalence in Iranian population in the age range of 20-60 years. MATERIALS AND METHODS All eligible brain dead liver transplant donors were enrolled in the survey from March 21, 2011 to March 21, 2013 in Imam-Khomeini hospital Complex. Eligible participants were donors aged 20 to 60 years without any obvious history of liver disease. Liver needle biopsy was performed at the end of the transplant operation; time zero biopsy. We calculated the prevalence of NAFLD among brain-dead donors. Moreover, the frequency of NASH was calculated based on the NAS (NAFLD Activity Score). RESULTS Among 116 cases, two were diagnosed as probable NASH. There was a significant association between NAFLD and male gender (P = 0.04). Moreover, we found a higher steatosis level in male gender. There was a significant association between NAFLD and BMI (P = 0.05). Those with BMI more than 27 had severe steatosis. CONCLUSIONS Our comprehensive literature review showed that our study was the first investigation in Iran and the region, which determined the prevalence of NAFLD based on tissue diagnosis. We believe that the prevalence of NAFLD/NASH in our donors can represent the overall prevalence in this age group in Iran.
Collapse
Affiliation(s)
- Ali Jafarian
- Hepatobiliary and Liver Transplantation Division, Department of General Surgery, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, IR Iran
- Corresponding Author: Ali Jafarian, Hepatobiliary and Liver Transplantation Division, Department of General Surgery, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, IR Iran. Tel/Fax: +98-2166581657, E-mail:
| | - Amirpasha Ebrahimi
- Hepatobiliary and Liver Transplantation Division, Department of General Surgery, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, IR Iran
| | - Farid Azmoudeh Ardalan
- Department of Pathology, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, IR Iran
| | - Habibollah Dashti
- Hepatobiliary and Liver Transplantation Division, Department of General Surgery, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, IR Iran
| | - Mojgan Rahimi
- Department of Anesthesiology and Intensive Care, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, IR Iran
| | - Mandana Salehi
- Hepatobiliary and Liver Transplantation Division, Department of General Surgery, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, IR Iran
| | - Mohsen Nasiri Toosi
- Gastroenterology Division, Internal Medicine Department, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, IR Iran
| |
Collapse
|
|
41
|
Li JF, Qu F, Zheng SJ, Wu HL, Liu M, Liu S, Ren Y, Ren F, Chen Y, Duan ZP, Zhang JL. Elevated plasma sphingomyelin (d18:1/22:0) is closely related to hepatic steatosis in patients with chronic hepatitis C virus infection. Eur J Clin Microbiol Infect Dis 2014; 33:1725-1732. [PMID: 24810965 DOI: 10.1007/s10096-014-2123-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Accepted: 04/09/2014] [Indexed: 12/20/2022]
Abstract
Hepatic steatosis affects disease progression in patients with chronic hepatitis C virus (HCV) infection. We investigated the plasma sphingolipid profile in patients with chronic hepatitis C (CHC) and whether there was an association between HCV-related steatosis and plasma sphingolipids. We used high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to analyze plasma sphingolipids in 120 interferon-naïve, non-diabetic, and non-obese CHC patients. Hepatic steatosis was defined as ≥5 % hepatocytes with fat based on histopathological analysis. Blood biochemical indicators and HCV load and genotype were also determined. Thirty-six (30.0 %) of 120 patients presented with hepatic steatosis Grades 1-3. Forty-four plasma sphingolipids were detected. Plasma sphingomyelin (SM) (d18:1/22:0) and ceramide (Cer) (d18:1/24:0)-1-P correlated with steatosis grade (r = 0.22, p = 0.015; r = -0.23, p = 0.012, respectively). SM (d18:1/22:0) [odds ratio (OR) = 1.12] and Cer (d18:1/24:0)-1-P (OR = 0.88) were independent factors for the presence of hepatic steatosis in CHC patients. The area under the curve (AUC) of SM (d18:1/22:0) and Cer (d18:1/24:0)-1-P was 0.637 and 0.638, respectively, to identify the presence of steatosis. Further analysis for genotype 2 CHC showed that only SM (d18:1/22:0) was independently linked to steatosis (OR = 1.21). The AUC of SM (d18:1/22:0) to identify hepatic steatosis in genotype 2 CHC was 0.726. Its sensitivity and negative predictive value reached 0.813 and 0.886, respectively. This study suggested that altered plasma SM (d18:1/22:0) was closely related to hepatic steatosis in chronic HCV infection, especially with genotype 2. Experimental studies are needed to determine further the underlying mechanisms responsible for these associations.
Collapse
Affiliation(s)
- J-F Li
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing, 100069, China
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
The prevalence of bright liver echo pattern in patients with chronic hepatitis C: correlation with steatosis and fibrosis. J Ultrasound 2014; 19:91-8. [PMID: 27298639 DOI: 10.1007/s40477-014-0114-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 06/11/2014] [Indexed: 12/17/2022] Open
Abstract
PURPOSE To evaluate the prevalence of bright liver echo pattern (BLP) on ultrasonography and its correlation with liver steatosis (LS), and fibrosis in patients with chronic hepatitis C. The usefulness of detecting skip areas for steatosis diagnosis has also been evaluated. METHODS The study included 88 patients with chronic hepatitis C (55 men, 33 women, average age 45.7 ± 11.2 years). Ultrasound examination was performed in all patients before liver biopsy. The presence of BLP was assessed and graded from 1 to 3. Hypoechogenic areas (skip areas) around the gallbladder or near the portal vein were also evaluated. Hepatic fibrosis was assessed using the Ishak fibrosis score. Steatosis was graded as follows: 1, 2, 3 (<30, 30-70, >70 % of hepatocytes affected, respectively). RESULTS Fifty-three of the 88 patients (60 %) showed BLP (40 grade 1, 13 grades 2 or 3). Skip areas were found in 14 patients (16 %). Histological steatosis was observed in 40 patients (45 %) and in 10 of them (25 %) was grades 2 and 3 (4 and 6 patients, respectively). As regards fibrosis, 2 patients showed F0, 34 F1, 28 F2, 20 F3, 4 F4, none of them F5 and F6. BLP of grades 2 or 3 and presence of skip areas were strongly correlated with LS (P = 0.00007 and P = 0.00003, respectively). No correlation was found between BLP and fibrosis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of BLP for LS were 75, 50, 56, 68 and 61 %, respectively. When BLP of grades 2 and 3 and LS of 30 % or more were correlated, the sensitivity, specificity, PPV, NPV and accuracy of BLP were 72, 96, 61, 96 and 90 %, respectively. As regards skip areas the sensitivity, specificity, PPV, NPV and accuracy for LS were 35, 100, 100, 64 and 70 %, respectively. CONCLUSIONS In a well-defined group of patients with chronic hepatitis C, the detection of BLP grades 2 and 3 has a good sensitivity and high specificity for high grades of steatosis. A high specificity but low sensitivity for liver steatosis was also found for skip areas, whereas mild fibrosis does not seem to correlate with the hyperechogenicity of the liver.
Collapse
|
|
43
|
Chan CHY, Hansen RD, Gilliver RS, Jones BE. Sustained virological response following chronic hepatitis C treatment is associated with improvement in insulin resistance. Intern Med J 2014; 43:656-62. [PMID: 23506416 DOI: 10.1111/imj.12136] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2012] [Accepted: 03/10/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND Insulin resistance (IR) is a key factor in the development of hepatic steatosis and fibrosis in chronic hepatitis C virus infection. Little is known about the impact of viral clearance on IR. AIM The aim of this study was to determine the impact of viral clearance on IR. METHODS Eighty-six patients treated according to standard clinical practice at an Australian teaching hospital between 2003 and 2007 were prospectively studied. Demographic, biochemical and histological data were collected. RESULTS The mean pretreatment homeostatic model assessment-IR (HOMA-IR) was similar in the sustained virological response (SVR) and non-SVR groups (2.7 ± 0.5 and 2.8 ± 0.4, respectively), and both values were consistent with significant IR. There was a significant improvement in HOMA-IR (from 3.0 ± 1.0 to 2.2 ± 0.5, P = 0.04) at the end of treatment in the SVR group only. This trended towards significance at 6 months post-treatment. Multiple regression analysis found improvement in both gamma-glutamyl transpeptidase and alanine aminotransferase predicted improvement in HOMA-IR when controlled for other potential factors (P = 0.01). CONCLUSIONS Hepatitis C virus clearance is associated with improvement in IR. Although baseline hepatic fibrosis is a predictor of IR, changes in IR appear to be independent of changes in liver fibrosis. Treatment-related improvement in gamma-glutamyl transpeptidase and alanine aminotransferase seen with improved IR may be a possible marker of reduction of hepatic oxidative stress.
Collapse
Affiliation(s)
- C H Y Chan
- Department of Gastroenterology and Hepatology, Royal North Shore Hospital, Sydney, Australia
| | | | | | | |
Collapse
|
|
44
|
Central portalization correlates with fibrosis but not with risk factors for nonalcoholic steatohepatitis in steatotic chronic hepatitis C. Int J Hepatol 2014; 2014:329297. [PMID: 25525520 PMCID: PMC4265703 DOI: 10.1155/2014/329297] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Accepted: 11/10/2014] [Indexed: 12/23/2022] Open
Abstract
Concomitant steatosis in chronic hepatitis C is associated with fibrosis and unfavorable treatment outcome. Central zone injury in nonalcoholic steatohepatitis (NASH) manifests as central portalization, with centrizonal microvessels and ductular reaction. We investigated whether central portalization in steatotic HCV biopsies would identify patients with metabolic risk factors for NASH. Liver biopsies with chronic hepatitis C and >10% steatosis (n = 65) were evaluated for the degree of steatosis, zonation of steatosis, fibrosis, and nonalcoholic fatty liver disease (NAFLD) activity score. The presence of centrizonal microvessels, sinusoidal capillarization, ductular reaction, and CK7 positive intermediate-phenotype hepatocytes were evaluated by CD34 and CK7 immunostain. The degree of steatosis and fibrosis showed a positive correlation. Additional positive correlations were noted between centrizonal angiogenesis and NAFLD activity score and central portalization and fibrosis. However, neither central portalization nor zonation of steatosis identified patients with metabolic risk factors for NASH. Therefore, central portalization cannot be used as a surrogate marker to identify patients with metabolic risk factors for NASH in steatotic HCV biopsies. The mechanism of centrizonal injury in steatotic HCV hepatitis is not solely attributable to the metabolic risk factors for NASH.
Collapse
|
|
45
|
Cheng FKF, Torres DM, Harrison SA. Hepatitis C and lipid metabolism, hepatic steatosis, and NAFLD: still important in the era of direct acting antiviral therapy? J Viral Hepat 2014; 21:1-8. [PMID: 24329852 DOI: 10.1111/jvh.12172] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) have an individual prevalence of 1.8-3% and at least 30%, respectively, in the United States. It is therefore not surprising that there is overlap between these two common chronic liver diseases, although the relationship appears to go beyond isolated co-existence. Hepatic steatosis is a common feature of CHC infection and can be related to both metabolic and viral specific factors. Steatosis in the setting of nongenotype 3 CHC has been predictive of response to therapy prior to the advent of the direct acting antiviral medications (DAAs). Similarly, lipid metabolism appears important in response to CHC treatment. The pathways for both lipid homeostasis and NAFLD as it pertains to CHC infection as well as the utilization of statin therapy in CHC infection will be reviewed with a focus on the relevance of these topics in the era of DAA therapy.
Collapse
Affiliation(s)
- F-K F Cheng
- Division of Gastroenterology, Department of Medicine, Walter Reed National Military Medical Center, Washington, DC, USA
| | | | | |
Collapse
|
|
46
|
Mohan P, Barton BA, Narkewicz MR, Molleston JP, Gonzalez-Peralta RP, Rosenthal P, Murray KF, Haber B, Schwarz KB, Goodman ZD. Evaluating progression of liver disease from repeat liver biopsies in children with chronic hepatitis C: a retrospective study. Hepatology 2013; 58:1580-6. [PMID: 23703847 PMCID: PMC5493995 DOI: 10.1002/hep.26519] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2012] [Accepted: 05/01/2013] [Indexed: 12/13/2022]
Abstract
UNLABELLED Clinical and histologic progression of liver disease in untreated children with chronic hepatitis C virus (HCV) infection is poorly documented. The aim of this retrospective study was to characterize changes in liver histology over time in a cohort of HCV-infected children who had more than one liver biopsy separated by over 1 year. Forty-four untreated children without concurrent liver diseases, who had repeat liver biopsies at eight U.S.-based medical centers, were included. Biopsies were scored by a single pathologist for inflammation, fibrosis, and steatosis and were correlated with demographic data including age at biopsy, time from infection to biopsies, and laboratory values such as serum alanine aminotransferase (ALT). Mode of transmission was vertical in 25 (57%) and from transfusions in 17 children (39%). Genotype 1 was present in 30/35 (84%) children. The mean age at first and final biopsy was 8.6 and 14.5 years, respectively, and the mean interval between biopsies was 5.8 ± 3.5 years. Duration of infection to biopsy was 7.7 and 13.5 years, respectively. Laboratory values did not change significantly between the biopsies. Inflammation was minimal in about 50% at both timepoints. Fibrosis was absent in 16% in both biopsies, limited to portal/periportal in 73% in the first biopsy, and 64% in the final biopsy. Between the two biopsies, the proportion of patients with bridging fibrosis/cirrhosis increased from 11% to 20% (P = 0.005). CONCLUSION Although in aggregate this cohort did not show significant histologic progression of liver disease over 5 years, 29.5% (n = 13) of children showed an increase in severity of fibrosis. These findings may have long-term implications for the timing of follow-up biopsies and treatment decisions.
Collapse
Affiliation(s)
- Parvathi Mohan
- Children’s National Medical Center, The George Washington School of Medicine, Washington DC
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Sagnelli C, Uberti-Foppa C, Pasquale G, De Pascalis S, Coppola N, Albarello L, Doglioni C, Lazzarin A, Sagnelli E. Factors influencing liver fibrosis and necroinflammation in HIV/HCV coinfection and HCV monoinfection. Infection 2013; 41:959-967. [PMID: 23839212 DOI: 10.1007/s15010-013-0502-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2013] [Accepted: 06/25/2013] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To define differences in liver histology between HIV/HCV coinfection and HCV monoinfection, and to investigate possible causative factors. METHODS Liver biopsies (LBs) from 440 consecutive HIV/HCV-coinfected patients (Group HIV/HCV) and 374 consecutive HCV-monoinfected patients (Group HCV) were evaluated for necroinflammation and fibrosis (Ishak) by a pathologist unaware of the clinical and laboratory data. All patients were HBsAg-negative, with no history of alcohol abuse and naïve to anti-HCV treatment. At LB, 78.4% of patients in Group HIV/HCV were on an antiretroviral regimen. RESULTS HIV/HCV-coinfected patients compared to the HCV-monoinfected patients were younger (p < 0.0001), more frequently males (p < 0.0001), and had HCV genotype 3 (p < 0.0001); they showed a good immunological condition (CD4+ cell count: 518 ± 166 cells/mm(3)). Patients in Group HIV/HCV more frequently showed a fibrosis score ≥4 (27.5 vs. 20.6%, p < 0.05) and a necroinflammation score ≥9 (25.9 vs. 13.4%; p < 0.0001). The prevalence of patients with fibrosis score ≥4 was significantly higher in older age classes in both Group HIV/HCV (p < 0.005) and Group HCV (p < 0.05). A necroinflammation score ≥9 was significantly higher in older age classes only in Group HIV/HCV (p < 0.05). A multivariate analysis for Group HIV/HCV revealed that the patient age and nadir of CD4+ cell count were independently associated to higher degrees of fibrosis, the patient age and antiretroviral treatment were associated to higher degrees of necroinflammation, and HCV genotype 3 was associated to higher degrees of steatosis. CONCLUSION The data suggest a need for early anti-HCV treatment in both HCV-monoinfected and HIV/HCV-coinfected patients.
Collapse
Affiliation(s)
- C Sagnelli
- Clinic of Infectious Diseases and Department of Pathology, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy,
| | | | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Interobserver concordance in controlled attenuation parameter measurement, a novel tool for the assessment of hepatic steatosis on the basis of transient elastography. Eur J Gastroenterol Hepatol 2013; 25:905-11. [PMID: 23459105 DOI: 10.1097/meg.0b013e32835f4c3d] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The combination of transient elastometry with a controlled attenuation parameter (CAP) is available to evaluate hepatic steatosis (HS) along with liver stiffness. AIMS To assess the concordance of CAP measurements between two independent observers in patients infected by HIV and/or hepatitis virus, as well as to determine the concordance of classification of the grade of HS using two cut-off values. MATERIALS AND METHODS In a cross-sectional prospective study, CAP-enabled transient elastometry acquisitions were performed by two independent observers in patients with HIV or hepatitis virus infection. The interobserver concordance between the CAP examinations was assessed using the intraclass correlation coefficient and the concordance in the classification of patients in the grades of HS was characterized using the κ index. RESULTS A total of 118 patients were included. Twenty (17%) patients were HIV monoinfected, 44 (37.3%) were hepatitis C virus monoinfected, and 52 (44%) had HIV/hepatitis C virus coinfection. The median (Q1-Q3) of the absolute difference of CAP values between the two observers was 20 (10-41) dB/m. The overall intraclass correlation coefficient was 0.84 (95% confidence interval: 0.77-0.88). The corresponding figures for liver stiffness measurements were 0.9 (0.4-2.6) kPa and 0.96 (95% confidence interval: 0.94-0.97). The κ indexes for the concordance of classification for the presence of HS, cut-off of 215 dB/m, and significant HS, cut-off of 252 dB/m, were 0.53 and 0.62, respectively. CONCLUSION The determination of HS by means of CAP in HIV and/or hepatitis virus infection represents an observer-independent and easily performable method. However, the use of cut-off values for the classification of patients is suboptimal.
Collapse
|
|
49
|
Castera L. Natural History of Chronic HCV Infection and Non‐Invasive Assessment of Hepatic Fibrosis. VIRAL HEPATITIS 2013:341-352. [DOI: 10.1002/9781118637272.ch23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
50
|
Macaluso FS, Maida M, Minissale MG, Li Vigni T, Attardo S, Orlando E, Petta S. Metabolic factors and chronic hepatitis C: a complex interplay. BIOMED RESEARCH INTERNATIONAL 2013; 2013:564645. [PMID: 23956991 PMCID: PMC3730187 DOI: 10.1155/2013/564645] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2013] [Accepted: 06/29/2013] [Indexed: 12/15/2022]
Abstract
In the last years, several lines of evidence showed how metabolic factors may influence the natural history of patients with chronic hepatitis C. Chronic HCV infection is able to perturb the metabolic homeostasis of the host, in a context of complex interactions where pre-existent metabolic status and genetic background play an important role, allowing us to state that HCV infection is a systemic disease. In this review, we discuss the most recent lines of evidence on the main metabolic factors that are known to be associated with CHC, namely, insulin resistance/type 2 diabetes, steatosis, visceral obesity, atherosclerosis, vitamin D, menopause, fructose and coffee intake, lipoproteins, methylenetetrahydrofolate reductase status, and hyperuricaemia. In particular, we focus on the pathophysiological mechanisms underlying the correlation between HCV infection and metabolic disorders, the impact of metabolic factors on the progression of liver and non-liver-related diseases, and, on the contrary, the possible influence of chronic HCV infection on metabolic features. In this setting, the importance of a multifaceted evaluation of CHC patients and a prompt correction of modifiable metabolic risk factors should be emphasized.
Collapse
Affiliation(s)
- Fabio Salvatore Macaluso
- Section of Gastroenterology, DiBiMIS, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy.
| | | | | | | | | | | | | |
Collapse
|