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1
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Shetty S, Suvarna R, Ambrose Fistus V, Modi S, Pappachan JM. Cardiovascular implications of metabolic dysfunction-associated fatty liver disease and type 2 diabetes mellitus: A meta-analysis. World J Hepatol 2025; 17:105706. [DOI: 10.4254/wjh.v17.i5.105706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 03/31/2025] [Accepted: 04/22/2025] [Indexed: 05/27/2025] Open
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) are independent risk factors for the development of cardiovascular disease (CVD) and an exaggerated CVD risk is expected when both diseases co-exist. Therefore, thorough risk stratification is important to inform better clinical practice decisions based on good quality evidence for patient with MAFLD and T2DM.
AIM To identify the CVD and cardiovascular event (CVE) risk in a systematic review when MAFLD and T2DM co-exist to inform better clinical practice decisions.
METHODS A systematic review was performed by compiling data by searching PubMed, EMBASE and Cochrane Library databases. Quality appraisal of retrieved studies and the meta-analysis were performed using Joanna Briggs Institute (JBI) tool and RevMan 5.4 software respectively. The effect indicators for CVE and CVD risk were expressed as odds ratios (OR) and 95%CI with P-values < 0.05 as significant.
RESULTS Fourteen (5 cohort and 9 cross-sectional) studies with 370013 participants were included in this review. The meta-analysis of CVE showed that the risk of CVE in T2DM was higher in the MAFLD group when compared to the non-MAFLD group [OR 1.28 (95%CI, 1.04–1.56) P = 0.02] with follow up duration ranging between 5-6 years. The prevalence of CVD in the metanalysis of cross-sectional studies was found to be higher [OR 1.47 (95%CI, 1.21–1.78) P = 0.0001] in T2DM with MAFLD when compared to T2DM without MAFLD. Significant heterogeneity exists due to variations in study design, methodologies, and MAFLD diagnostic criteria, which may have influenced the study's findings.
CONCLUSION The presence of MAFLD in T2DM increased the risk of CVE. The prevalence of CVD is higher in T2DM with MAFLD as compared to T2DM without MAFLD. Large well-designed multicentric long-term prospective studies are necessary to appropriately risk stratify the cardiovascular effect of the MAFLD in T2DM patients.
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Affiliation(s)
- Sahana Shetty
- Department of Endocrinology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Renuka Suvarna
- Department of Endocrinology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Vanessa Ambrose Fistus
- Department of Medicine, Royal Preston Hospital, Lancashire Teaching Hospitals National Health Service Trust, Preston PR2 9HT, Lancashire, United Kingdom
| | - Shivam Modi
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals National Health Service Trust, Preston PR2 9HT, Lancashire, United Kingdom
| | - Joseph M Pappachan
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
- Department of Endocrinology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, 576104, India
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Jabeen S, Khan R, Alrashed MM, Ullah S, Nabi G, Ullah MI, Waqar AB, Attia KA, Kimiko I. Modulation of glucose metabolism and insulin resistance following hepatitis C virus clearance via direct-acting antivirals. Sci Rep 2025; 15:14663. [PMID: 40287451 PMCID: PMC12033326 DOI: 10.1038/s41598-025-97827-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 04/07/2025] [Indexed: 04/29/2025] Open
Abstract
The positive sense RNA virus, hepatitis C virus (HCV), is affiliated with the Flaviviridae family. Approximately 1% of people around the globe experience the impact of the HCV, which can coax them into potentially fatal conditions, including cirrhosis and carcinoma. The second-highest hepatitis C infection burden lies in Pakistan. The case of a HCV-infected patient who additionally has obesity or concurrent medical conditions like diabetes, HBV infection, or HIV infection is susceptible to becoming direr. Direct-acting antiviral medications replaced interferons as a staple of the treatment plan since they have fewer, milder side effects and a higher SVR rate in patients. The present study sought to assess the modifications to glucose homeostasis in non-diabetic chronic HCV-infected patients getting DAA treatment and the factors that independently pertain to insulin resistance. The study enrolled 250 patients, with 190 individuals having HCV-positive PCR results. The analysis included CBC, LFTs, glycaemic and insulin measurements, and the insulin resistance index calculation. Key cardiometabolic risk factors crucial for defining MASLD were assessed, including BMI measurement, evaluation of type 2 diabetes, and lipid profile analysis. The same tests were repeated following DAA therapy, and HOMA-IR was computed to compare pre-and post-treatment results. Among the 250 recruited patients, 190 were detected as HCV positive by the PCR assay, 57% (110 patients) were women, 43% (80 patients) were men, and patients were 47 years old on average. The patients showed high BMI (average 26.28 kg/m2) and signs of severe insulin resistance (HOMA-IR > 2.5). Multivariable logistic regression analysis pointed out that elevated baseline levels of triglycerides, ALT, ALP, cholesterol, and total bilirubin were independently associated with high insulin resistance. A notable improvement in HOMA-IR from 13.63 ± 2.63 to 3.16 ± 1.52 (p < 0.005) was spotted after administering interferon-free antiviral therapy for 3 months. The presence of high BMI, hyperlipidemia, and elevated levels of ALP, ALT, and AST in non-diabetic HCV-infected patients were independently associated with IR. In patients who previously had a higher IR index, there was a decrease in the HOMA-IR index after infection clearance by direct-acting antivirals.
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Affiliation(s)
- Sajida Jabeen
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
| | - Ramsha Khan
- University Institute of Medical Lab Technology, The University of Lahore, Lahore, Pakistan
| | - May M Alrashed
- Department of Clinical Laboratory Science, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
- Center of Excellence in Biotechnology Research, King Saud University, Riyadh, Saudi Arabia.
| | - Sajjad Ullah
- University Institute of Medical Lab Technology, The University of Lahore, Lahore, Pakistan.
| | - Ghulam Nabi
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
| | - Malik Ihsan Ullah
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
| | - Ahmed Bilal Waqar
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
| | - Kotb A Attia
- Center of Excellence in Biotechnology Research, King Saud University, Riyadh, Saudi Arabia
| | - Itoh Kimiko
- Institute of Science and Technology, Niigata University, Ikarashi-2, Nishiku, Niigata, Japan
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Sinclair S, Shearen S, Ghobrial Y, Trad G, Abdul Basit S, Shih D, Ryan JK. Review of the Effects of Antiviral Therapy on Hepatitis B/C-Related Mortality and the Regression of Fibrosis. Viruses 2024; 16:1531. [PMID: 39459866 PMCID: PMC11512229 DOI: 10.3390/v16101531] [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: 08/16/2024] [Revised: 09/19/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
Hepatitis B and Hepatitis C are viral causes of Hepatitis that lead to significant worldwide mortality and morbidity through the sequelae of fibrosis and hepatocellular carcinoma. In this review, we have summarized recent studies that have examined the effects of antiviral therapy on the regression of fibrosis and the reduction in mortalities associated with the viruses. Antiviral therapy significantly decreases mortality and induces the regression of fibrosis.
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Affiliation(s)
| | | | | | | | | | | | - John K. Ryan
- Comprehensive Digestive Institute of Nevada, Las Vegas, NV 89148, USA (S.A.B.); (D.S.)
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4
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Murakawa M, Nakagawa M, Nishimura H, Kaneko S, Miyoshi M, Kawai-Kitahata F, Nitta S, Tsuchiya J, Shimizu T, Watakabe K, Mochida T, Inada K, Iizuka Y, Sakai H, Sakurai Y, Sato A, Azuma S, Kawamura T, Maeyashiki C, Kurosaki M, Kusano F, Watanabe H, Kurata H, Karakama Y, Fujiwara T, Nagata Y, Tanaka T, Kakinuma S, Okamoto R, Asahina Y. High serum gamma-glutamyltransferase level after hepatitis C virus elimination is a risk factor for the development of hepatocellular carcinoma. Hepatol Res 2024. [PMID: 39073391 DOI: 10.1111/hepr.14094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 06/24/2024] [Accepted: 06/25/2024] [Indexed: 07/30/2024]
Abstract
AIM Gamma-glutamyltransferase (GGT) is known as an oxidative stress marker, induced by alcohol consumption and metabolic disorders, and is reported as a predictor of hepatocellular carcinoma (HCC) development after hepatitis C virus (HCV) elimination. However, it is not clear whether GGT serves simply as a surrogate marker for overlapping metabolic diseases or reflects HCV-specific carcinogenicity. We investigated the association between GGT and hepatocarcinogenesis after achieving a sustained viral response (SVR), accounting for drinking habits or diabetes, and examined predisposing factors associated with GGT levels after SVR. METHODS This is a prospective, multicenter, and observational study using the database of 1001 patients after HCV eradication with direct-acting antiviral agents. The association of GGT at SVR with cumulative HCC development was examined in a multivariate analysis using Cox proportional hazard models after adjustment for covariates including alcohol and diabetes. The association between oxidative stress markers or genetic factors and GGT levels was analyzed. RESULTS High GGT levels at SVR were associated with HCC development (HR] 2.38, 95% CI 1.10-5.17). This association was also significant when restricted to patients without alcohol consumption or diabetes (HR 8.38, 95% CI 2.87-24.47). GGT levels were correlated with serum growth differentiation factor 15 levels, a marker of mitochondrial dysfunction. Single-nucleotide polymorphisms of ZNF827 and GDF15 were associated with high GGT levels. CONCLUSIONS High GGT levels at SVR were associated with HCC development after accounting for alcohol consumption and diabetes. GGT levels are influenced by genetic predisposition and may reflect mitochondrial dysfunction after HCV eradication.
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Affiliation(s)
- Miyako Murakawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mina Nakagawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
- Institute of Education, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hisaaki Nishimura
- Department of Public Health, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shun Kaneko
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Masato Miyoshi
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Fukiko Kawai-Kitahata
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Sayuri Nitta
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Jun Tsuchiya
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Taro Shimizu
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Keiya Watakabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Tomohiro Mochida
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kento Inada
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Iizuka
- Department of Gastroenterology and Hepatology, Kashiwa Municipal Hospital, Chiba, Japan
| | - Hideki Sakai
- Department of Gastroenterology and Hepatology, Kashiwa Municipal Hospital, Chiba, Japan
| | - Yuki Sakurai
- Department of Gastroenterology and Hepatology, Showa General Hospital, Tokyo, Japan
| | - Ayako Sato
- Department of Gastroenterology and Hepatology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | - Seishin Azuma
- Department of Gastroenterology and Hepatology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | - Takahiro Kawamura
- Department of Gastroenterology and Hepatology, JA Toride Medical Center, Ibaraki, Japan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Fumihiko Kusano
- Department of Gastroenterology and Hepatology, Tsuchiura Kyodo General Hospital, Ibaraki, Japan
| | - Hideki Watanabe
- Department of Gastroenterology and Hepatology, Yokosuka Kyosai Hospital, Kanagawa, Japan
| | - Hitoshi Kurata
- Department of Gastroenterology and Hepatology, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan
| | - Yuko Karakama
- Department of Gastroenterology and Hepatology, Tokyo Kyosai Hospital, Tokyo, Japan
| | - Takeo Fujiwara
- Department of Public Health, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yuki Nagata
- Department of Human Genetics and Disease Diversity, Tokyo Medical Dental University, Tokyo, Japan
| | - Toshihiro Tanaka
- Department of Human Genetics and Disease Diversity, Tokyo Medical Dental University, Tokyo, Japan
| | - Sei Kakinuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Clinical and Diagnostic Laboratory Science, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ryuichi Okamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
- Department for Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
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Gonzales-Zamora JA, Quispe-Vicuña C, Reategui-Garcia ME, Araoz-Salinas JM, Ccami-Bernal F, Morocho-Alburqueque N, Espinoza-Herreros JP, Layme J, Aquino-Sandoval G, Campos VYM, Alave J. Identifying Gaps in the Treatment Guidelines for Hepatitis C in Peru to Meet International Standards: A Narrative Review. J Clin Med 2024; 13:3867. [PMID: 38999433 PMCID: PMC11242551 DOI: 10.3390/jcm13133867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 06/16/2024] [Accepted: 06/25/2024] [Indexed: 07/14/2024] Open
Abstract
Hepatitis C virus still represents a major cause of morbidity and mortality worldwide. In Peru, two national practice guidelines for the management of this infection were published more than 5 years ago; however, the latest breakthroughs in the treatment make it necessary to update these guidelines. We reviewed the most recent recommendations of the international guidelines and compared them with the current Peruvian guidelines. We found major differences, such as the use of Glecaprevir/Pibrentasvir as a first-line therapy, which is contemplated in the World Health Organization guideline, and recommended by American and European guidelines, but is not considered in the Peruvian guidelines. Another crucial difference lies in the management of patients with chronic kidney disease, who are treated nowadays with a variety of direct-acting antivirals, with no restrictions on the use of Sofosbuvir-based regimens in first-world countries, an approach that has not been adopted in Peru. We believe that standardization of the recommendations of the Peruvian guidelines is imperative, including the new therapeutic strategies that have emerged in recent years. We also suggest conducting a cost effectiveness analysis in the Peruvian context to allow for the implementation of new antivirals, and to achieve a better control of hepatitis C in the country.
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Affiliation(s)
- Jose A. Gonzales-Zamora
- Division of Infectious Diseases, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, USA;
- Peruvian American Medical Society (PAMS), Albuquerque, NM 87111, USA; (J.M.A.-S.); (J.L.); (V.Y.M.C.)
| | | | - Martín E. Reategui-Garcia
- School of Medicine, Universidad Nacional de la Amazonía Peruana, Iquitos 16000, Peru; (M.E.R.-G.); (G.A.-S.)
| | - Julieta M. Araoz-Salinas
- Peruvian American Medical Society (PAMS), Albuquerque, NM 87111, USA; (J.M.A.-S.); (J.L.); (V.Y.M.C.)
| | - Fabricio Ccami-Bernal
- School of Medicine, Universidad Nacional de San Agustín de Arequipa, Arequipa 04001, Peru;
| | | | | | - Josue Layme
- Peruvian American Medical Society (PAMS), Albuquerque, NM 87111, USA; (J.M.A.-S.); (J.L.); (V.Y.M.C.)
- School of Medicine, Universidad Nacional Mayor de San Marcos, Lima 15001, Peru
| | - Gabriel Aquino-Sandoval
- School of Medicine, Universidad Nacional de la Amazonía Peruana, Iquitos 16000, Peru; (M.E.R.-G.); (G.A.-S.)
- Sociedad Científica de Estudiantes de Medicina de la Amazonía Peruana (SOCIEMAP), Universidad Nacional de la Amazonía Peruana, Iquitos 16000, Peru
| | - Victor Y. Melt Campos
- Peruvian American Medical Society (PAMS), Albuquerque, NM 87111, USA; (J.M.A.-S.); (J.L.); (V.Y.M.C.)
- Department of Community Health and Family Medicine, College of Medicine, University of Florida, Jacksonville, FL 32209, USA
| | - Jorge Alave
- School of Medicine, Universidad Peruana Union, Lima 15464, Peru
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6
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Cespiati A, Coelho Rodrigues I, Santos I, Policarpo S, Carvalhana S, Fracanzani AL, Cortez-Pinto H. Effect of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, and associated metabolic comorbidities: A systematic review. Liver Int 2024; 44:1075-1092. [PMID: 38385567 DOI: 10.1111/liv.15876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 12/11/2023] [Accepted: 02/08/2024] [Indexed: 02/23/2024]
Abstract
BACKGROUND AND AIMS The beneficial effect of Hepatitis C virus (HCV) eradication by direct antiviral agents (DAAs) on liver fibrosis is well defined. Despite this, the impact of viral eradication in both hepatic and extra-hepatic metabolic features is underreached. This systematic review aimed to synthesize the evidence on the impact of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, glucidic impairment, dyslipidaemia, and weight gain. METHODS A systematic search of the existing literature (up to December 2022) identified 97 original studies that fulfilled the inclusion criteria. RESULTS Whereas total cholesterol and low-density lipoprotein (LDL) seem to increase after viral eradication, the cardiovascular damage expressed as carotid plaques and intima-media thickness seems to improve. Otherwise, the effect on liver steatosis, glucidic homeostasis, and weight seems to be strictly dependent on the presence of baseline metabolic disorders. CONCLUSION Despite high heterogeneity and relatively short follow-up of included studies, we can conclude that the presence of metabolic risk factors should be strictly evaluated due to their impact on liver steatosis, glucidic and lipid homeostasis, and on weight gain to better identify patients at risk of liver disease progression despite the virus eradication.
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Affiliation(s)
- Annalisa Cespiati
- Unit of Medicine and Metabolic Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Inês Coelho Rodrigues
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
| | - Inês Santos
- Laboratório de Nutrição, Faculdade de Medicina, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal
- Faculdade de Medicina, Instituto de Saúde Ambiental (ISAMB), Universidade de Lisboa, Lisbon, Portugal
| | - Sara Policarpo
- Laboratório de Nutrição, Faculdade de Medicina, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal
- Serviço de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, E.P.E., Lisbon, Portugal
| | - Sofia Carvalhana
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Anna Ludovica Fracanzani
- Unit of Medicine and Metabolic Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Helena Cortez-Pinto
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
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Méndez-Sánchez N, Coronel-Castillo CE, Ramírez-Mejía MM. Chronic Hepatitis C Virus Infection, Extrahepatic Disease and the Impact of New Direct-Acting Antivirals. Pathogens 2024; 13:339. [PMID: 38668294 PMCID: PMC11053783 DOI: 10.3390/pathogens13040339] [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: 03/06/2024] [Revised: 04/12/2024] [Accepted: 04/14/2024] [Indexed: 04/29/2024] Open
Abstract
Chronic hepatitis C virus infection is an important cause of liver cirrhosis, hepatocellular carcinoma and death. Furthermore, it is estimated that about 40-70% of patients develop non-hepatic alterations in the course of chronic infection. Such manifestations can be immune-related conditions, lymphoproliferative disorders and metabolic alterations with serious adverse events in the short and long term. The introduction of new Direct-Acting Antivirals has shown promising results, with current evidence indicating an improvement and remission of these conditions after a sustained virological response.
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Affiliation(s)
- Nahum Méndez-Sánchez
- Unit Liver Research, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico;
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico
| | | | - Mariana Michelle Ramírez-Mejía
- Unit Liver Research, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico;
- Plan of Combined Studies in Medicine (PECEM MD/PhD), Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico
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8
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Hung HY, Lai HH, Lin HC, Chen CY. The impact of sofosbuvir/velpatasvir/voxilaprevir treatment on serum hyperglycemia in hepatitis C virus infections: a systematic review and meta-analysis. Ann Med 2023; 55:463-479. [PMID: 36655629 PMCID: PMC9858431 DOI: 10.1080/07853890.2023.2168745] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure. Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection in diabetics with a history of hypoglycemia could improve insulin resistance due to HCV clearance. However, some studies have shown that SOF/VEL/VOX causes grade 3 hyperglycemia and other adverse events, which contradicts the findings of other DAA studies. AIM To analyze the incidence of grade 3 hyperglycemia of SOF/VEL/VOX for chronic HCV infection. METHODS We searched electronic databases from the inception of each database until October 2021. A random-effects model was employed to pool data. The study was conducted according to the PRISMA guidelines, and quality assessment was performed by using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs). The study protocol was registered on the INPLASY database (Registration No. 2021120109). RESULTS Five RCTs were included in this review. Overall, 49 of 2315 patients had grade 3 hyperglycemia with a risk ratio of 0.015 (95% confidence interval, 0.010-0.020; p < .001), and the incidence risk ratio (IRR) for cirrhosis compared to without cirrhosis was 12.000 (95% confidence interval: 0.727-198.160), the HCV genotype 3-genotype 1 IRR was 4.13 (95% confidence interval: 1.52-11.22) in subgroup analysis. No significant differences were found within the other subgroups, in prior DAA treatment experience, and in treatment duration. CONCLUSION Although the incidence of hyperglycemia was rare in diabetic patients with HCV, it is recommended that glucose levels be closely monitored during the first 3 months of therapy and that diabetes medication be modified if necessary.
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Affiliation(s)
- Hsuan-Yu Hung
- Department of Pharmacy, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.,School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hui-Hsiung Lai
- Department of Pharmacy, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
| | - Hui-Chuan Lin
- Department of Pharmacy, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
| | - Chung-Yu Chen
- School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.,Master Program in Clinical Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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9
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Wu VCC, Huang CH, Wang CL, Lin MH, Kuo TY, Chang CH, Wu M, Chen SW, Chang SH, Chu PH, Wu CS, Lin YS. Cardiovascular outcomes in hepatitis C virus infected patients treated with direct acting antiviral therapy: a retrospective multi-institutional study. EUROPEAN HEART JOURNAL. CARDIOVASCULAR PHARMACOTHERAPY 2023; 9:507-514. [PMID: 37170917 DOI: 10.1093/ehjcvp/pvad030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 04/04/2023] [Accepted: 04/25/2023] [Indexed: 05/13/2023]
Abstract
BACKGROUND Chronic hepatitis C virus (HCV) infection is associated with increased cardiovascular risks. We aimed to investigate the impact of direct acting antiviral (DAA) on HCV-associated cardiovascular events. METHODS In this retrospective cohort study, patients with the diagnosis of chronic HCV were retrieved from multi-institutional electronic medical records, where diagnosis of HCV was based on serum HCV antibody and HCV-RNA test. The patients eligible for analysis were then separated into patients with DAA treatment and patient without DAA treatment. Primary outcomes included acute coronary syndrome, heart failure (HF), venous thromboembolism (VTE), stroke, cardiovascular death, major adverse cardiovascular event (MACE), and all-cause mortality. Outcomes developed during follow-up were compared between DAA treatment and non-DAA treatment groups. RESULTS There were 41 565 patients with chronic HCV infection identified. After exclusion criteria applied, 1984 patients in the DAA treatment group and 413 patients in the non-DAA treatment group were compared for outcomes using inverse probability of treatment weighting. Compared to patients in non-DAA treatment group, patients in DAA treatment group were associated with significantly decreased HF (hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.44-0.97, P = 0.035), VTE (HR: 0.19, 95% CI: 0.07-0.49, P = 0.001), MACE (HR: 0.73, 95% CI 0.59-0.92, P = 0.007), and all-cause mortality (HR: 0.50, 95% CI: 0.38-0.67, P < 0.001) at 3-year follow-up. CONCLUSIONS Chronic HCV patients treated with DAA experienced lower rates of cardiovascular events and all-cause mortality than those without treatment. The reduction of VTE was the most significant impact of DAA treatment among the cardiovascular outcomes.
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Affiliation(s)
- Victor Chien-Chia Wu
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Chien-Hao Huang
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan
| | - Chun-Li Wang
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Meng-Hung Lin
- Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital Chiayi Branch, Chiayi 613016, Taiwan
| | - Ting-Yu Kuo
- Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital Chiayi Branch, Chiayi 613016, Taiwan
| | - Chih-Hsiang Chang
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
- Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan
| | - Michael Wu
- Divison of Cardiovascular Medicine, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, Providence, RI 02903, USA
| | - Shao-Wei Chen
- Department of Cardiothoracic and Vascular Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan
| | - Shang-Hung Chang
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan
| | - Pao-Hsien Chu
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333423, Taiwan
| | - Cheng-Shyong Wu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
| | - Yu-Sheng Lin
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
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10
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Mohamed Abdelnajid D, Elmowafy AY, Rostaing L, Elrakaiby MT. Prediction of response to sofosbuvir-based therapy using serum interleukin-12 and single nucleotide polymorphism of the interleukin 28B gene as predictive factors in HCV positive genotype-4 patients. Medicine (Baltimore) 2023; 102:e34125. [PMID: 37443472 PMCID: PMC10344568 DOI: 10.1097/md.0000000000034125] [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: 03/03/2023] [Accepted: 06/07/2023] [Indexed: 07/15/2023] Open
Abstract
Some hepatitis-C virus patients have resistance to direct-acting-antivirals (DAAs). Genetic polymorphisms have been associated with drug resistance. This study aimed to evaluate the role of interleukin (IL)-28B gene polymorphism and IL-12 levels as predictors for a response to sofosbuvir/ribavirin (SOF/RBV) with (triple-therapy) or without (dual-therapy) Peg-alpha-interferon. 92 hepatitis C virus (HCV)/RNA (+)-patients treated with dual (n = 72) or triple (n = 20) therapy. IL28B genetic polymorphism and IL-12 level assessments. 30.4% of the patients were IL28B C/C genotype, 56.5% C/T-genotype, and 13% T/T-genotype. Mean baseline IL-12 levels were 27.5 ± 3.0 pg/mL. Rapid viral response was achieved in 86/92 patients. All patients achieved end-of-treatment virologic response. The 12- and 24-week sustained virologic responses (SVR) were achieved in 76 patients (82.6%), that is, a relapse was found in 16 patients (17.4%). 8 and 12-weeks after antiviral therapy, IL-12 levels decreased significantly, and became comparable to those of the control-group. That drop in IL-12 levels was similar across the dual- and triple-therapy patients. Finally, logistic regression analysis showed that the increase in baseline aspartate aminotransferase (AST) and T/T genotyping had an independent effect on increasing the probability a SVR failing in both dual- and triple-therapy groups (P = .0007 and P = .02, respectively). Single-nucleotide polymorphism (SNP) in IL-28B and IL-12 levels play roles as predictors in DAAs resistance.
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Affiliation(s)
- Doaa Mohamed Abdelnajid
- Department of Microbiology and Immunology, Military Medical Academy, Cairo, Egypt
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Kasr Al-Aini, Cairo, Egypt
| | | | - Lionel Rostaing
- Department of Nephrology, Hemodialysis, Apheresis, and Kidney Transplantation, CHU Grenoble-Alpes, France
- Grenoble Alpes University, Grenoble, France
| | - Marwa T. Elrakaiby
- Department of Microbiology and Immunology, Military Medical Academy, Cairo, Egypt
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11
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Huang X, Chen H, Wen S, Dong M, Zhou L, Yuan X. Therapeutic Approaches for Nonalcoholic Fatty Liver Disease: Established Targets and Drugs. Diabetes Metab Syndr Obes 2023; 16:1809-1819. [PMID: 37366486 PMCID: PMC10290856 DOI: 10.2147/dmso.s411400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 06/16/2023] [Indexed: 06/28/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), as a multisystemic disease, is the most prevalent chronic liver disease characterized by extremely complex pathogenic mechanisms and multifactorial etiology, which often develops as a consequence of obesity, metabolic syndrome. Pathophysiological mechanisms involved in the development of NAFLD include diet, obesity, insulin resistance (IR), genetic and epigenetic determinants, intestinal dysbiosis, oxidative/nitrosative stress, autophagy dysregulation, hepatic inflammation, gut-liver axis, gut microbes, impaired mitochondrial metabolism and regulation of hepatic lipid metabolism. Some of the new drugs for the treatment of NAFLD are introduced here. All of them achieve therapeutic objectives by interfering with certain pathophysiological pathways of NAFLD, including fibroblast growth factors (FGF) analogues, peroxisome proliferator-activated receptors (PPARs) agonists, glucagon-like peptide-1 (GLP-1) agonists, G protein-coupled receptors (GPCRs), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), farnesoid X receptor (FXR), fatty acid synthase inhibitor (FASNi), antioxidants, etc. This review describes some pathophysiological mechanisms of NAFLD and established targets and drugs.
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Affiliation(s)
- Xiaojing Huang
- Graduate School of Fudan University, Shanghai, People’s Republic of China
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China
| | - Huiling Chen
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China
| | - Song Wen
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China
| | - Meiyuan Dong
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China
| | - Ligang Zhou
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China
| | - Xinlu Yuan
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China
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12
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Casas-Deza D, Espina S, Martínez-Sapiña A, Del Moral-Bergos R, Garcia-Sobreviela MP, Lopez-Yus M, Calmarza P, Bernal-Monterde V, Arbones-Mainar JM. Triglyceride-rich lipoproteins and insulin resistance in patients with chronic hepatitis C receiving direct-acting antivirals. Atherosclerosis 2023; 375:59-66. [PMID: 37245427 DOI: 10.1016/j.atherosclerosis.2023.05.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 05/03/2023] [Accepted: 05/03/2023] [Indexed: 05/30/2023]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV) interferes with carbohydrate and lipid metabolism causing cardiovascular disease and insulin resistance (IR). Direct-acting antivirals (DAAs) are highly effective for the eradication of HCV, with positive effects on metabolic health although paradoxically associated with increased total and LDL-cholesterol. The aims of this study were 1) to characterize dyslipidemia (lipoprotein content, number, and size) in naive HCV-infected individuals and 2) to evaluate the longitudinal association of metabolic changes and lipoparticle characteristics after DAA therapy. METHODS We conducted a prospective study with one-year follow-up. 83 naive outpatients treated with DAAs were included. Those co-infected with HBV or HIV were excluded. IR was analyzed using the HOMA index. Lipoproteins were studied by fast-protein liquid chromatography (FPLC) and Nuclear Magnetic Resonance Spectroscopy (NMR). RESULTS FPLC analysis showed that lipoprotein-borne HCV was only present in the VLDL region most enriched in APOE. There was a lack of association between HOMA and total cholesterol or cholesterol carried by LDL or HDL at baseline. Alternatively, a positive association was found between HOMA and total circulating triglycerides (TG), as well as with TG transported in VLDL, LDL, and HDL. HCV eradication with DAAs resulted in a strong and significant decrease in HOMA (-22%) and HDL-TG (-18%) after one-year follow-up. CONCLUSIONS HCV-dependent lipid abnormalities are associated with IR and DAA therapy can reverse this association. These findings may have potential clinical implications as the HDL-TG trajectory may inform the evolution of glucose tolerance and IR after HCV eradication.
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Affiliation(s)
- Diego Casas-Deza
- Gastroenterology Department, Miguel Servet University Hospital, 50009, Zaragoza, Spain; Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, Miguel Servet University Hospital, 50009, Zaragoza, Spain; Instituto de Investigación Sanitaria (IIS) Aragon, 50009, Zaragoza, Spain
| | - Silvia Espina
- Gastroenterology Department, Miguel Servet University Hospital, 50009, Zaragoza, Spain; Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, Miguel Servet University Hospital, 50009, Zaragoza, Spain; Instituto de Investigación Sanitaria (IIS) Aragon, 50009, Zaragoza, Spain
| | - Ana Martínez-Sapiña
- Clinical Microbiology Department, Miguel Servet University Hospital, 50009, Zaragoza, Spain
| | - Raquel Del Moral-Bergos
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, Miguel Servet University Hospital, 50009, Zaragoza, Spain; Instituto de Investigación Sanitaria (IIS) Aragon, 50009, Zaragoza, Spain; Instituto Aragones de Ciencias de la Salud (IACS), 50009, Zaragoza, Spain
| | - Maria Pilar Garcia-Sobreviela
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, Miguel Servet University Hospital, 50009, Zaragoza, Spain; Instituto de Investigación Sanitaria (IIS) Aragon, 50009, Zaragoza, Spain
| | - Marta Lopez-Yus
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, Miguel Servet University Hospital, 50009, Zaragoza, Spain; Instituto Aragones de Ciencias de la Salud (IACS), 50009, Zaragoza, Spain
| | - Pilar Calmarza
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009, Zaragoza, Spain; Clinical Biochemistry Department, Miguel Servet University Hospital, 50009, Zaragoza, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto Salud Carlos III, 28029, Madrid, Spain
| | - Vanesa Bernal-Monterde
- Gastroenterology Department, Miguel Servet University Hospital, 50009, Zaragoza, Spain; Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, Miguel Servet University Hospital, 50009, Zaragoza, Spain; Instituto de Investigación Sanitaria (IIS) Aragon, 50009, Zaragoza, Spain.
| | - Jose M Arbones-Mainar
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, Miguel Servet University Hospital, 50009, Zaragoza, Spain; Instituto de Investigación Sanitaria (IIS) Aragon, 50009, Zaragoza, Spain; Instituto Aragones de Ciencias de la Salud (IACS), 50009, Zaragoza, Spain; CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, 28029, Madrid, Spain.
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13
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Chun HS, Lee M, Lee JS, Lee HW, Kim BK, Park JY, Kim DY, Ahn SH, Lee YH, Kim JH, Kim SU. Metabolic dysfunction associated fatty liver disease identifies subjects with cardiovascular risk better than non-alcoholic fatty liver disease. Liver Int 2023; 43:608-625. [PMID: 36585250 DOI: 10.1111/liv.15508] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 12/21/2022] [Accepted: 12/27/2022] [Indexed: 01/01/2023]
Abstract
BACKGROUND AND AIMS Cardiovascular disease (CVD) is the main cause of mortality in subjects with non-alcoholic fatty liver disease (NAFLD). We investigated the association between CVD risk and metabolic dysfunction-associated fatty liver disease (MAFLD) or NAFLD and the influence of significant liver fibrosis on the CVD risk. METHODS Subjects who underwent a comprehensive medical check-up were recruited (2014-2019). Significant liver fibrosis was defined using NAFLD fibrosis score, fibrosis-4 index, aspartate aminotransferase to platelet ratio index, or FibroScan-aspartate aminotransferase score. High probability of atherosclerotic CVD (ASCVD) was defined as ASCVD risk score > 10%. RESULTS Of the study population (n = 78 762), 27 047 (34.3%) and 24 036 (30.5%) subjects had MAFLD and NAFLD respectively. A total of 1084 (4.0%) or 921 (3.8%) subjects had previous CVD history in MAFLD or NAFLD subgroup respectively. The previous CVD history and high probability of ASCVD were significantly higher in MAFLD or NAFLD subgroup with significant liver fibrosis than in the other groups (all p < .001). In multivariable analysis, MAFLD was independently associated with previous CVD history after adjusting for confounders (adjusted odds ratio [aOR] = 1.10, p = .038), whereas NAFLD was not (all p > .05). MAFLD (aOR = 1.40) or NAFLD (aOR = 1.22) was independently associated with high probability of ASCVD after full adjustment respectively (all p < .001). Significant liver fibrosis was independently associated with previous CVD history and high probability of ASCVD after adjustment in MAFLD or NAFLD subgroup respectively (all p < .05). CONCLUSION MAFLD might better identify subjects with CVD risk than NAFLD. Fibrosis assessment might be helpful for detailed prognostication in subjects with MAFLD.
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Affiliation(s)
- Ho Soo Chun
- Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, South Korea
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, South Korea
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Yong-Ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Ji-Hye Kim
- Department of Health Promotion, Yonsei University Health System, Seoul, South Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
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14
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Chen CH, Shen CH, Wei KL, Xu HW, Chen WM, Chang KC, Huang YT, Hsieh YY, Lu SN, Hung CH, Chang TS. Factors Associated with Large Renal Function Decline in Patients with Chronic Hepatitis C Successfully Treated with Direct-Acting Antiviral Therapy. Diagnostics (Basel) 2023; 13:diagnostics13030473. [PMID: 36766578 PMCID: PMC9914858 DOI: 10.3390/diagnostics13030473] [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: 12/25/2022] [Revised: 01/09/2023] [Accepted: 01/16/2023] [Indexed: 02/01/2023] Open
Abstract
The findings regarding changes in renal function in patients with hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are controversial. This study attempted to identify the factors associated with the large decline in renal function following DAA treatment. This retrospective cohort study included patients treated with DAAs at Chiayi and Yunlin Chang Gung Hospitals, Taiwan, from 1 January 2017 to 31 October 2020. Estimated glomerular filtration rate (eGFR) data were collected within 90 days prior to DAA therapy and 2 years after the confirmation of a sustained virologic response (SVR). We performed multiple logistic regression to evaluate the clinical or laboratory parameters associated with a large eGFR decline (≥10%). Among the enrolled 606 patients, the mean eGFR at the baseline and endpoint were 84.11 ± 24.38 and 78.88 ± 26.30 mL/min/1.73 m2, respectively (p < 0.001). The factors associated with a large eGFR decline 2 years after the SVR included hypertension (OR: 1.481; 95% CI: 1.010-2.173, p = 0.044) and a higher baseline eGFR (OR: 1.016; 95% CI: 1.007-1.024, p < 0.001). A higher albumin level reduced the risk of a large eGFR decline (OR: 0.546; 95% CI: 0.342-0.872, p = 0.011). In the patients with HCV treated with DAAs, a larger renal function decline was more commonly observed in those with hypertension, a lower (but within normal range) albumin level, and a higher baseline eGFR, while DAA treatment had no effect. The clinical significance of these findings has to be further defined. Although some risk factors associated with chronic kidney disease may be alleviated after DAA treatment, the regular control and follow-up of risk factors and renal function are still recommended in at-risk patients after HCV eradication.
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Affiliation(s)
- Chun-Hsien Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Chien-Heng Shen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Kuo-Liang Wei
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
| | - Huang-Wei Xu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Wei-Ming Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
| | - Kao-Chi Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Yu-Ting Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Yung-Yu Hsieh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Sheng-Nan Lu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
| | - Chao-Hung Hung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
| | - Te-Sheng Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
- Correspondence:
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15
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Caturano A, Galiero R, Loffredo G, Vetrano E, Medicamento G, Acierno C, Rinaldi L, Marrone A, Salvatore T, Monda M, Sardu C, Marfella R, Sasso FC. Effects of a Combination of Empagliflozin Plus Metformin vs. Metformin Monotherapy on NAFLD Progression in Type 2 Diabetes: The IMAGIN Pilot Study. Biomedicines 2023; 11:biomedicines11020322. [PMID: 36830859 PMCID: PMC9952909 DOI: 10.3390/biomedicines11020322] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/18/2023] [Accepted: 01/20/2023] [Indexed: 01/26/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) comprises a heterogeneous group of metabolic liver diseases and is characterized by the presence of steatosis in at least 5% of hepatocytes. The aim of our study was to assess the effect of the combination therapy of empagliflozin + metformin vs. metformin monotherapy on NAFLD progression in type 2 diabetic (T2DM) patients. Sixty-three metformin-treated T2DM patients who were SGLT2i-naïve and had an ultrasound diagnosis of NAFLD (aged 60.95 ± 11.14 years; males, 57.1%) were included in the present analysis. Thirty-three started the combination therapy. All patients were observed for 6 months and routinely monitored with anthropometry, blood biochemistry, and FibroScan®/CAP. At the 6-month follow-up, the combination therapy group presented a significant reduction in BMI (30.83 ± 3.5 vs. 28.48 ± 3.25), glycated hemoglobin (8.2 (7.4-8.8)) vs. 7.2 (6.8-7.9), ALT (68.5 (41.5-88.0) vs. 45.00 (38.00, 48.00)), CAP parameter (293.5 (270.0-319.25) vs. 267.00 (259.50, 283.75)) and steatosis degree (p = 0.001) in comparison with the control group, whose parameters remained almost stable over time. In patients affected by T2DM, the combination of empagliflozin + metformin vs. metformin monotherapy ameliorated liver steatosis, ALT levels, body weight, and glycated hemoglobin after a 6-month follow-up.
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Affiliation(s)
- Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Raffaele Galiero
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Giuseppe Loffredo
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Erica Vetrano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Giulia Medicamento
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Carlo Acierno
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Teresa Salvatore
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Marcellino Monda
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Celestino Sardu
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
- Correspondence: ; Tel.: +39-(08)-15665010
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16
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Vitale A, Svegliati-Baroni G, Ortolani A, Cucco M, Dalla Riva GV, Giannini EG, Piscaglia F, Rapaccini G, Di Marco M, Caturelli E, Zoli M, Sacco R, Cabibbo G, Marra F, Mega A, Morisco F, Gasbarrini A, Foschi FG, Missale G, Masotto A, Nardone G, Raimondo G, Azzaroli F, Vidili G, Oliveri F, Pelizzaro F, Ramirez Morales R, Cillo U, Trevisani F, Miele L, Marchesini G, Farinati F. Epidemiological trends and trajectories of MAFLD-associated hepatocellular carcinoma 2002-2033: the ITA.LI.CA database. Gut 2023; 72:141-152. [PMID: 34933916 DOI: 10.1136/gutjnl-2021-324915] [Citation(s) in RCA: 89] [Impact Index Per Article: 44.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 11/29/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort. METHODS We analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC. RESULTS MAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002-2003, to 77.3% and 28.9% in 2018-2019, respectively, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006). CONCLUSIONS The prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.
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Affiliation(s)
- Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Gianluca Svegliati-Baroni
- Liver Disease and Transplant Unit, Polytechnic University of Marche, Ancona, Italy
- Obesity Center, Polytechnic University of Marche, Ancona, Italy
| | - Alessio Ortolani
- Department of Gastroenterology, Azienda Ospedaliera Marche Nord Pesaro, Pesaro, Italy
| | - Monica Cucco
- Liver Disease and Transplant Unit, Polytechnic University of Marche, Ancona, Italy
- Department of Gastroenterology, Polytechnic University of Marche, Ancona, Italy
| | - Giulio V Dalla Riva
- School of Mathematics and Statistics University of Canterbury, Statistics University of Canterbury, Canterbury, New Zealand
| | - Edoardo G Giannini
- Department of Internal Medicine, Gastroenterology Unit, University of Genova, IRCCS Policlinico San Martino, Genoa, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gianludovico Rapaccini
- Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | | | | | - Marco Zoli
- Department of Medical and Surgical Sciences, Internal Medicine-Zoli Unit, Alma Mater Studiorum - Università di Bologna, Padova, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Puglia, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Florence, Florence, Italy
| | - Andrea Mega
- Gastroenterology Unit, Ospedale Generale Regionale di Bolzano, Bolzano, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples Federico II, Portici, Italy
| | - Antonio Gasbarrini
- Internal Medicine, Gastroenterology, and Liver Unit, University Hospital Agostino Gemelli, Roma, Lazio, Italy
| | | | - Gabriele Missale
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Emilia-Romagna, Italy
| | - Alberto Masotto
- Gastroenterology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Veneto, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, Federico II University Hospital, Napoli, Italy
| | - Giovanni Raimondo
- Clinical and Experimental Medicine, University Hospital of Messina, Messina, Italy
| | - Francesco Azzaroli
- Division of Gastroenterology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gianpaolo Vidili
- Department of Clinical and Experimental Medicine, Universita degli Studi di Sassari, Sassari, Italy
| | - Filippo Oliveri
- Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine, University of Pisa, Pisa, Italy
| | - Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Rafael Ramirez Morales
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Franco Trevisani
- Division of Medical Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Luca Miele
- Internal Medicine and Gastroenterology, Fondazione Policlinico Gemelli, Rome, Italy
- Internal Medicine, Universita Cattolica del Sacro Cuore, Roma, Italy
| | - Giulio Marchesini
- Department of Medical & Surgical Sciences, University of Bologna Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Bologna, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
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Impact of eradication of hepatitis C virus on liver-related and -unrelated diseases: morbidity and mortality of chronic hepatitis C after SVR. J Gastroenterol 2022; 58:299-310. [PMID: 36585501 DOI: 10.1007/s00535-022-01940-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 12/05/2022] [Indexed: 12/31/2022]
Abstract
Hepatitis C virus infection is characterized by chronic liver inflammation and fibrogenesis, leading to end-stage liver failure and hepatocellular carcinoma over the course of 20 to 30 years. It seems not only the chronicity of hepatitis C but also the presence of the virus in non-hepatic tissues creates a favorable environment for the potential development of pathogenic impacts on extrahepatic systems and organs. Numerous extra-hepatic manifestations have been reported in association with HCV infection, all of which can substantially affect morbidity, mortality, and quality of life. With the recent development of DAAs, antiviral treatment can cure almost all patients with HCV infection, even those intolerant of or unresponsive to IFN treatment, and several large multicenter studies have confirmed the association of DAA-induced SVR with reductions in liver-related and liver-unrelated complications, such as cardiovascular events, end stage renal disease, and so on. Because, in addition to liver-related diseases, extrahepatic lesions are threatening for patients, it is important to eradicate the virus before these progress and affect life prognosis; in other words, patients should be treated before reaching the point of no return. Tailored surveillance with biomarkers such as M2BPGi and Ang-2, which can be used to identify patients with an elevated risk of EHM, and early prevention or treatment for these patients could improve the morbidity, mortality and QOL. Advancement of both basic and clinical research in this field including the development of more precise biomarkers is highly anticipated.
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Salvatore T, Galiero R, Caturano A, Rinaldi L, Criscuolo L, Di Martino A, Albanese G, Vetrano E, Catalini C, Sardu C, Docimo G, Marfella R, Sasso FC. Current Knowledge on the Pathophysiology of Lean/Normal-Weight Type 2 Diabetes. Int J Mol Sci 2022; 24:ijms24010658. [PMID: 36614099 PMCID: PMC9820420 DOI: 10.3390/ijms24010658] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/21/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023] Open
Abstract
Since early times, being overweight and obesity have been associated with impaired glucose metabolism and type 2 diabetes (T2D). Similarly, a less frequent adult-onset diabetes in low body mass index (BMI) people has been known for many decades. This form is mainly found in developing countries, whereby the largest increase in diabetes incidence is expected in coming years. The number of non-obese patients with T2D is also on the rise among non-white ethnic minorities living in high-income Western countries due to growing migratory flows. A great deal of energy has been spent on understanding the mechanisms that bind obesity to T2D. Conversely, the pathophysiologic features and factors driving the risk of T2D development in non-obese people are still much debated. To reduce the global burden of diabetes, we need to understand why not all obese people develop T2D and not all those with T2D are obese. Moreover, through both an effective prevention and the implementation of an individualized clinical management in all people with diabetes, it is hoped that this will help to reduce this global burden. The purpose of this review is to take stock of current knowledge about the pathophysiology of diabetes not associated to obesity and to highlight which aspects are worthy of future studies.
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Affiliation(s)
- Teresa Salvatore
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
| | - Raffaele Galiero
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
| | - Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
| | - Livio Criscuolo
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
| | - Anna Di Martino
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
| | - Gaetana Albanese
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
| | - Erica Vetrano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
| | - Christian Catalini
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
| | - Celestino Sardu
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
| | - Giovanni Docimo
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
- Mediterrannea Cardiocentro, I–80122 Napoli, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I–80138 Naples, Italy
- Correspondence:
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19
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Onikanni SA, Lawal B, Bakare OS, Ajiboye BO, Ojo OA, Farasani A, Kabrah SM, Batiha GES, Conte-Junior CA. Cancer of the Liver and its Relationship with Diabetes mellitus. Technol Cancer Res Treat 2022; 21:15330338221119743. [PMID: 36533882 PMCID: PMC9772979 DOI: 10.1177/15330338221119743] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
A high increase witnessed in type II diabetes mellitus (T2DM) globally has increasingly posed a serious threat to global increases in liver cancer with the association between diabetes mellitus type II and the survival rate in liver cancer patients showing unstable findings. An increase in the development and progression of chronic liver disease from diabetes mellitus patients may be connected to cancer of the liver with several links such as Hepatitis B and C virus and heavy consumption of alcohol. The link between T2DM patients and liver cancer is centered on non-alcoholic fatty liver disease (NAFLD) which could be a serious threat globally if not clinically addressed. Several reports identified metformin treatment as linked to a lower risk of liver cancer prognosis while insulin treatment or sulphonylureas posed a serious threat. Mechanistically, the biological linkage between diabetes type II mellitus and liver cancer are still complex to understand with only the existence of a relationship between NAFLD and high level of energy intake and diabetes mellitus induces hepatic damage, increased liver weight thereby causes multiple pro-inflammatory cytokines that lead to the development of liver cancer. Therefore, this review gives an account of the pathophysiological importance of liver cancer position with T2DM, with the role of NAFLD as an important factor that bridges them.
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Affiliation(s)
- Sunday Amos Onikanni
- Department of Chemical Sciences, Biochemistry Unit, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria,College of Medicine, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan,Sunday Amos Onikanni, College of Medicine, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
| | - Bashir Lawal
- PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei,Graduate Institute for Cancer Biology & Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei
| | | | - Basiru Olaitan Ajiboye
- Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, Ekiti State, Nigeria
| | - Oluwafemi Adeleke Ojo
- Phytomedicine, Molecular Toxicology, and Computational Biochemistry Research Laboratory (PMTCB-RL), Department of Biochemistry, Bowen University, Iwo, 232101, Nigeria
| | - Abdullah Farasani
- Biomedical Research Unit, Medical Research Center, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia,Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Saeed M Kabrah
- Department of Laboratory Medicine Faculty of Applied medical sciences, Umm Al-Qura University, Kingdom of Saudi Arabia
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, AlBeheira, Egypt
| | - Carlos Adam Conte-Junior
- Analytical and Molecular Laboratorial Center (CLAn), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ, 21941-909, Brazil
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20
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Sparvoli JMH, Sparvoli AC, Dumith SDC, Pereira AA, Paula ALMD, Garcia L, Belarmino V, Hora VPD, Martínez AMBD, Gonçalves CV. Impact of hepatitis C virus eradication with direct-acting antivirals on glycidic metabolism. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2022; 67:314-322. [PMID: 36468927 DOI: 10.20945/2359-3997000000543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Objective To compare the glucose metabolism of patients with chronic hepatitis C virus infection treated with direct-acting antivirals (DAAs) in pretreatment and sustained viral response (SVR) periods. Materials and methods This was an intervention pre-post study of 273 patients with chronic hepatitis C virus infection treated with DAAs from March 2018 to December 2019. Glycidic metabolism was evaluated through homeostasis model assessment (HOMA) - insulin resistance (IR) and HOMA-β indices and assessments of insulinemia and HbA1c levels. These parameters were analyzed with a T test by paired comparison of the means of the variables and Wilcoxon's test paired for the median; in the variables with an abnormal distribution, the Z score was generated for the mean in both the pretreatment and SVR periods. Statistical significance was considered at p ≤ 0.05. Results Among 273 participants, 125 (45.8%) had prediabetes, and 50 (18.3%) had diabetes. In SVR, there was a significant increase in platelets, albumin, alkaline phosphatase, cholesterol and triglycerides and a significant decrease in aspartate aminotransferase, alanine aminotransferase, gamma GT and bilirubin. The HOMA-IR and HOMA-β indices increased in SVR from 1.95 to 2.29 (p = 0.087) and 71.20 to 82.60 (p = 0.001), respectively. Insulinemia increased from 7.60 μU/mL to 8.90 μU/mL (p = 0.011). HbA1c decreased from 5.6 to 5.4 (p < 0.001). Among patients with prediabetes and those with diabetes, the reduction in HbA1c values was significant (p = 0.006 and p = 0.026, respectively). Conclusion SVR significantly impacts and leads to improvement in glucose metabolism in patients with chronic liver disease induced by hepatitis C virus.
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21
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Peng H, Hou M, Wu Z, Wang J, Zhou M, Zhuang X, Xing J, Tao Q, Huang L, Zhou F, Zhang S, Feng Q, Hou Y, Yu Q. Plasma exosomal miR-122 regulates the efficacy of metformin via AMPK in type 2 diabetes and hepatocellular carcinoma. Heliyon 2022; 8:e11503. [DOI: 10.1016/j.heliyon.2022.e11503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 08/25/2022] [Accepted: 11/01/2022] [Indexed: 11/16/2022] Open
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22
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Ma W, Wu W, Wen W, Xu F, Han D, Lyu J, Huang Y. Association of NAFLD with cardiovascular disease and all-cause mortality: a large-scale prospective cohort study based on UK Biobank. Ther Adv Chronic Dis 2022; 13:20406223221122478. [PMID: 36159632 PMCID: PMC9493675 DOI: 10.1177/20406223221122478] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 08/03/2022] [Indexed: 12/02/2022] Open
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome, sharing the similar cardiometabolic risk factors with cardiovascular disease (CVD). Whether NAFLD by itself is associated with increased cardiovascular events and death remain an issue to debate. This study aimed to further investigate the association between NAFLD and adverse CVD outcomes. METHODS Participants were followed up until the end of 2020 in current analysis. NAFLD is defined using fatty liver index (FLI). Cox proportional hazard model was used to analyze the association between NAFLD and all-cause mortality, major adverse cardiovascular events (MACEs), CVD mortality, fatal/nonfatal acute myocardial infarction (AMI), and fatal/nonfatal stroke. C-index was calculated to evaluate the model enhancement when adding NAFLD factor. RESULTS After screening the data of 502,492 participants in the original cohort, 215,245 eligible participants were included in this study for MACEs outcome. Compared with non-NAFLD participants, the multivariable adjusted hazard ratios of NAFLD group was 1.25 (1.14-1.36) for MACEs; 1.14 (1.08-1.20) for all-cause mortality; 1.61(1.42-1.82) for CVD mortality; 1.58(1.19-2.11) for AMI mortality; and 1.18 (0.85-1.64) for stroke mortality. When adding FLI, C-index of NAFLD model improved for all-cause mortality, MACEs, and CVD mortality compared with that in the traditional CVD risk factor model. CONCLUSION NAFLD is an independent risk factor for all-cause mortality and adverse CVD outcomes. Based on the traditional CVD risk factor model, additionally screening NAFLD could improve the prediction efficiency for adverse CVD outcomes.
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Affiliation(s)
- Wen Ma
- Department of Cardiology, Shunde Hospital,
Southern Medical University, Foshan, P.R. China
- Department of Clinical Research, The First
Affiliated Hospital, Jinan University, Guangzhou, P.R. China
- School of Public Health, Xi’an Jiaotong
University Health Science Center, Xi’an, P.R. China
| | - Wentao Wu
- School of Public Health, Xi’an Jiaotong
University Health Science Center, Xi’an, P.R. China
| | - Weixing Wen
- Department of Cardiology, Shunde Hospital,
Southern Medical University, Foshan, P.R. China
| | - Fengshuo Xu
- School of Public Health, Xi’an Jiaotong
University Health Science Center, Xi’an, P.R. China
| | - Didi Han
- School of Public Health, Xi’an Jiaotong
University Health Science Center, Xi’an, P.R. China
| | - Jun Lyu
- Department of Clinical Research, The First
Affiliated Hospital, Jinan University, Guangzhou 510630, P.R. China
- Guangdong Provincial Key Laboratory of
Traditional Chinese Medicine Informatization (2021B1212040007), Guangzhou,
P.R. China
| | - Yuli Huang
- Department of Cardiology, Shunde Hospital,
Southern Medical University, Jiazi Road, Lunjiao, Shunde, Foshan 528300,
P.R. China
- The George Institute for Global Health,
Faculty of Medicine, University of New South Wales Sydney, Sydney, NSW,
Australia
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23
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Coronary Microvascular Dysfunction in Diabetes Mellitus: Pathogenetic Mechanisms and Potential Therapeutic Options. Biomedicines 2022; 10:biomedicines10092274. [PMID: 36140374 PMCID: PMC9496134 DOI: 10.3390/biomedicines10092274] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/04/2022] [Accepted: 09/09/2022] [Indexed: 11/16/2022] Open
Abstract
Diabetic patients are frequently affected by coronary microvascular dysfunction (CMD), a condition consisting of a combination of altered vasomotion and long-term structural change to coronary arterioles leading to impaired regulation of blood flow in response to changing cardiomyocyte oxygen requirements. The pathogenesis of this microvascular complication is complex and not completely known, involving several alterations among which hyperglycemia and insulin resistance play particularly central roles leading to oxidative stress, inflammatory activation and altered barrier function of endothelium. CMD significantly contributes to cardiac events such as angina or infarction without obstructive coronary artery disease, as well as heart failure, especially the phenotype associated with preserved ejection fraction, which greatly impact cardiovascular (CV) prognosis. To date, no treatments specifically target this vascular damage, but recent experimental studies and some clinical investigations have produced data in favor of potential beneficial effects on coronary micro vessels caused by two classes of glucose-lowering drugs: glucagon-like peptide 1 (GLP-1)-based therapy and inhibitors of sodium-glucose cotransporter-2 (SGLT2). The purpose of this review is to describe pathophysiological mechanisms, clinical manifestations of CMD with particular reference to diabetes, and to summarize the protective effects of antidiabetic drugs on the myocardial microvascular compartment.
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24
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Mare R, Sporea I. Gastrointestinal and Liver Complications in Patients with Diabetes Mellitus-A Review of the Literature. J Clin Med 2022; 11:5223. [PMID: 36079153 PMCID: PMC9456591 DOI: 10.3390/jcm11175223] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/25/2022] [Accepted: 09/01/2022] [Indexed: 11/29/2022] Open
Abstract
The number of diabetes mellitus patients has increased over the last few years in developing countries, along with obesity and sedentary lifestyle. Besides macroangiopathy and microangiopathy, damage to the nerve fibers of the peripheral nervous system is the most common chronic complication of diabetes. Digestive complications in diabetic patients represent a consequence of diabetic autonomic neuropathy involving the gastrointestinal tract, but unfortunately not always evaluated by diabetologists. Aside from the complications encountered in the digestive tract, patients with diabetes mellitus are prone to developing liver diseases. This review will describe the prevalence of these complications, the modality of diagnosis, and therapeutical solutions in order to reduce the risk of progression of these complications in diabetic subjects.
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Affiliation(s)
- Ruxandra Mare
- Department of Internal Medicine II, Gastroenterology and Hepatology Unit, Advanced Research Center in Gastroenterology and Hepatology “Victor Babes” University of Medicine and Pharmacy, 30041 Timisoara, Romania
- Regional Center of Research in Advanced Hepatology, Academy of Medical Science, 30041 Timisoara, Romania
| | - Ioan Sporea
- Department of Internal Medicine II, Gastroenterology and Hepatology Unit, Advanced Research Center in Gastroenterology and Hepatology “Victor Babes” University of Medicine and Pharmacy, 30041 Timisoara, Romania
- Regional Center of Research in Advanced Hepatology, Academy of Medical Science, 30041 Timisoara, Romania
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Rajewski P, Zarębska-Michaluk D, Janczewska E, Gietka A, Mazur W, Tudrujek-Zdunek M, Tomasiewicz K, Belica-Wdowik T, Baka-Ćwierz B, Dybowska D, Halota W, Lorenc B, Sitko M, Garlicki A, Berak H, Horban A, Orłowska I, Simon K, Socha Ł, Wawrzynowicz-Syczewska M, Jaroszewicz J, Deroń Z, Czauż-Andrzejuk A, Citko J, Krygier R, Piekarska A, Laurans Ł, Dobracki W, Białkowska J, Tronina O, Wietlicka-Piszcz M, Pawłowska M, Flisiak R. Hepatitis C Infection as a Risk Factor for Hypertension and Cardiovascular Diseases: An EpiTer Multicenter Study. J Clin Med 2022; 11:5193. [PMID: 36079122 PMCID: PMC9456581 DOI: 10.3390/jcm11175193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 08/17/2022] [Accepted: 08/29/2022] [Indexed: 11/21/2022] Open
Abstract
Hepatitis C infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, more and more is being heard about extrahepatic manifestations of the hepatitis C infection including its possible influence on the development of hypertension and cardiovascular diseases. In the given work, the frequency analysis of the incidence of hypertension and cardiovascular diseases among 2898 HCV-infected patients treated in Poland and the assessment of their relevance to the HCV genotype and the progression of liver fibrosis can be found. The prevalence of hypertension in the group of analyzed patients was 39% and was significantly associated with old age (OR = 1.08 (1.07-1.08)) and female sex, as well as the progression of liver fibrosis (OR = 1.54 (1.29-1.85)). Hypertension was found in 47.6% of patients with F4 fibrosis, 42.1% of patients with F3 fibrosis, and 25% of patients with F1 fibrosis. The incidence of cardiovascular disease in the studied group of patients was as follows: all incidents, 131 (4.52%); including ischemic heart disease 104, (3.95%); stroke, 2 (0.07%); atherosclerosis, 21 (0.72%); and aneurysms, 4 (0.14%). The obtained results prove that the prevalence of cardiovascular diseases is significantly associated with the advanced age of patients and the progression of liver fibrosis. The relevance of sex and the HCV genotype to the prevalence frequency of cardiovascular diseases in the study group has not been proven. This being the case, no differences in the frequency of their incidence depending on the HCV genotype, including genotype 3, was found. Hepatitis C infection as a non-classical risk factor for cardiovascular disease and hypertension does require further studying.
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Affiliation(s)
- Paweł Rajewski
- Department of Internal and Infectious Diseases, Provincial Infectious Disease Hospital, 85-030 Bydgoszcz, Poland
| | - Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Voivodship Hospital and Jan Kochanowski University, 25-369 Kielce, Poland
| | - Ewa Janczewska
- Hepatology Outpatient Clinic, ID Clinic, 41-400 Mysłowice, Poland
| | - Andrzej Gietka
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, 02-507 Warsaw, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Specialist Hospital in Chorzów, Medical University of Silesia, 40-055 Katowice, Poland
| | - Magdalena Tudrujek-Zdunek
- Department of Infectious Diseases and Hepatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases and Hepatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Teresa Belica-Wdowik
- Regional Center for Diagnosis and Treatment of Viral Hepatitis and Hepatology, John Paul II Hospital, 31-202 Kraków, Poland
| | - Barbara Baka-Ćwierz
- Regional Center for Diagnosis and Treatment of Viral Hepatitis and Hepatology, John Paul II Hospital, 31-202 Kraków, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland
| | - Waldemar Halota
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Department of Infectious Diseases, Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University Collegium Medicum, 30-252 Kraków, Poland
| | - Aleksander Garlicki
- Department of Infectious and Tropical Diseases, Jagiellonian University Collegium Medicum, 30-252 Kraków, Poland
| | - Hanna Berak
- Hospital for Infectious Diseases in Warsaw, 01-201 Warsaw, Poland
| | - Andrzej Horban
- Hospital for Infectious Diseases in Warsaw, 01-201 Warsaw, Poland
| | - Iwona Orłowska
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Krzysztof Simon
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Łukasz Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, 70-204 Szczecin, Poland
| | - Marta Wawrzynowicz-Syczewska
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, 70-204 Szczecin, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases, Medical University of Silesia in Katowice, 41-902 Bytom, Poland
| | - Zbigniew Deroń
- Ward of Infectious Diseases and Hepatology, Biegański Regional Specialist Hospital, 91-347 Łódź, Poland
| | - Agnieszka Czauż-Andrzejuk
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-089 Białystok, Poland
| | - Jolanta Citko
- Medical Practice of Infections, Regional Hospital, 10-561 Olsztyn, Poland
| | - Rafał Krygier
- Infectious Diseases and Hepatology Outpatient Clinic NZOZ “Gemini”, 62-571 Żychlin, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, 90-419 Łódź, Poland
| | - Łukasz Laurans
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, 70-204 Szczecin, Poland
- Multidisciplinary Regional Hospital in Gorzów Wielkopolski, 66-400 Gorzów Wielkopolski, Poland
| | | | - Jolanta Białkowska
- Department of Infectious and Liver Diseases, Medical University of Łódź, 90-419 Łódź, Poland
| | - Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Magdalena Wietlicka-Piszcz
- Department of Theoretical Fundations of Biomedical Sciences and Medical Informatics, Nicolaus Copernicus University, 87-100 Toruń, Poland
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-089 Białystok, Poland
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Ismaiel A, Ciobanu OS, Ismaiel M, Leucuta DC, Popa SL, David L, Ensar D, Al Srouji N, Dumitrascu DL. Atherogenic Index of Plasma in Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis. Biomedicines 2022; 10:2101. [PMID: 36140201 PMCID: PMC9495578 DOI: 10.3390/biomedicines10092101] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 08/24/2022] [Accepted: 08/25/2022] [Indexed: 02/07/2023] Open
Abstract
(1) Background: Approximately a billion people worldwide are affected by NAFLD, which places a high clinical burden and financial cost on society. Liver biopsy is the gold standard for diagnosing NAFLD, but its invasivity limits the early diagnosis of NAFLD. Hence, it is important to look for alternate techniques in detecting and diagnosing NAFLD. NAFLD is associated with atherosclerosis. The purpose of this study was to assess the effectiveness of the atherogenic index of plasma (AIP) as a non-invasive modality for predicting NAFLD. (2) Methods: A search using electronic databases PubMed, EMBASE, and Scopus was carried out to find observational studies, looking at research that had been published up until the date of 11 May 2022. The included studies' quality, risk of bias, and internal validity were evaluated using the QUADAS-2 quality assessment tool. The key summary outcomes were the mean difference (MD) and area under the curve (AUC). (3) Results: A total of eight studies (81,178 participants) were included in our review, while 17% of the included participants had NAFLD. A sex distribution of 57.8% men and 42.2% women was observed. The AIP between NAFLD and the controls was not significant (MD 0.212 [95% CI 0.231-0.655]). A significant MD in AIP between the males and females with NAFLD was observed (MD 0.246 [95% CI 0.098-0.395]). The AIP predicted NAFLD with an AUC of 0.764 as well as in males (AUC 0.761) and females (AUC 0.733). (4) Conclusions: There was a substantial MD in the AIP between both sexes, but there was no significant difference in the AIP values between patients with NAFLD and the controls. The AIP is a reliable biomarker for the diagnosis of NAFLD since its ability to predict the development of NAFLD was comparable to that of the other biomarkers.
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Affiliation(s)
- Abdulrahman Ismaiel
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Oana Sabina Ciobanu
- Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Mohamed Ismaiel
- Department of Surgery, St Michael’s Hospital, A96 D628 Dublin, Ireland
| | - Daniel-Corneliu Leucuta
- Department of Medical Informatics and Biostatistics, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania
| | - Stefan-Lucian Popa
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Liliana David
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Dilara Ensar
- Department of Medicine, Tallaght University Hospital, D24 NR0A Dublin, Ireland
| | - Nahlah Al Srouji
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Dan L. Dumitrascu
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
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Popescu MS, Firu DM, Pădureanu V, Mărginean CM, Mitruț R, Arsene AL, Mărgăritescu DN, Calina D, Docea AO, Mitruț P. Effects of Achieving Sustained Virologic Response after Direct-Acting Antiviral Agents on Long-Term Liver Fibrosis in Diabetics vs. in Non-Diabetic Patients with Chronic Hepatitis C Infection. Biomedicines 2022; 10:2093. [PMID: 36140194 PMCID: PMC9495608 DOI: 10.3390/biomedicines10092093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/22/2022] [Accepted: 08/24/2022] [Indexed: 12/15/2022] Open
Abstract
Because of the prevalence of HCV worldwide as well as its undiagnosed population due to a lack of screening, HCV can be considered a modern pandemic disease. In 2016, the World Health Organization (WHO) set goals for HCV's elimination that included a 65 percent reduction in mortality and an 80 percent reduction in newly infected cases by 2030. This study is a follow-up evaluation of 80 patients who received interferon-free treatment with direct-acting agents (DAA) for chronic HCV infection between the second half of 2017 and the end of 2018. They were assessed using a FibroMax test prior to DAA administration. Two pills/day of Ombitasvir 12.5 mg/Paritaprevir 75 mg/Ritonavir 50 mg and two pills/day of Dasabuvir 250 mg were given to the patients for 8 weeks. After treatment, all 80 patients in this study achieved an SVR (sustained virologic response), and the FibroMax test was performed three years later. Our study found that successfully treating HCV infection can play a significant role in reducing fibrosis in T2DM patients. In comparison to those of ActiTest and SteatoTest, FibroMax scores showed a significantly greater reduction in T2DM patients than in treatment-naive patients.
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Affiliation(s)
- Marian-Sorin Popescu
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan-Mihai Firu
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Vlad Pădureanu
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Cristina Maria Mărginean
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Radu Mitruț
- Department of Cardiology, University and Emergency Hospital, 050098 Bucharest, Romania
| | - Andreea Letitia Arsene
- Department of Microbiology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | | | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Paul Mitruț
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Casas-Deza D, Martínez-Sapiña A, Espina S, Garcia-Rodriguez B, Fernandez-Bonilla EM, Sanz-Paris A, Gonzalez-Irazabal Y, Bernal-Monterde V, Arbones-Mainar JM. Evaluation of Cardiovascular Risk Factors after Hepatitis C Virus Eradication with Direct-Acting Antivirals in a Cohort of Treatment-Naïve Patients without History of Cardiovascular Disease. J Clin Med 2022; 11:jcm11144049. [PMID: 35887813 PMCID: PMC9315656 DOI: 10.3390/jcm11144049] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 07/10/2022] [Accepted: 07/11/2022] [Indexed: 12/04/2022] Open
Abstract
Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes. Objective: To evaluate the impact of DAA treatment on different risk factors associated with cardiovascular disease. Methods: Prospective study with two-year follow-up. All patients treated with DAAs in the Liver Clinic of a tertiary hospital were included. Patients co-infected with HBV or HIV, with other causes of liver disease, on lipid-lowering treatment, pregnant, or with previous HCV treatment were excluded. The results were analyzed using linear mixed models. Results: 167 patients (53% female, 9.6% cirrhosis) were included. Low plasma lipid levels were observed before initiating HCV eradication. During the first year after treatment with DAA, we observed a sustained increase in cholesterol, triglycerides, HDL cholesterol (only in men), and LDL-cholesterol levels. An ameliorated glycemic control was also observed with a decrease in fasting insulin and reduced HOMA. Iron metabolism and coagulation function also improved with lower levels of serum ferritin and prothrombin activity; these biochemical changes resulted in a new diagnosis of hypercholesterolaemia in 17.4% of patients, requiring initiation of statins in 15%. Two non-fatal cardiovascular events were observed during the first 2 years of follow-up. Conclusions: DAA treatments returned plasma lipids to the normal range without increasing either the occurrence of cardiovascular events or the consumption of lipid-lowering medication beyond what is normal in a sex- and age-matched population.
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Affiliation(s)
- Diego Casas-Deza
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (D.C.-D.); (S.E.); (E.M.F.-B.)
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (B.G.-R.); (A.S.-P.); (Y.G.-I.)
| | - Ana Martínez-Sapiña
- Clinical Microbiology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain;
| | - Silvia Espina
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (D.C.-D.); (S.E.); (E.M.F.-B.)
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (B.G.-R.); (A.S.-P.); (Y.G.-I.)
| | - Beatriz Garcia-Rodriguez
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (B.G.-R.); (A.S.-P.); (Y.G.-I.)
- Clinical Biochemistry Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain
| | - Eva M. Fernandez-Bonilla
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (D.C.-D.); (S.E.); (E.M.F.-B.)
| | - Alejandro Sanz-Paris
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (B.G.-R.); (A.S.-P.); (Y.G.-I.)
- Nutrition Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain
| | - Yolanda Gonzalez-Irazabal
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (B.G.-R.); (A.S.-P.); (Y.G.-I.)
- Clinical Biochemistry Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain
| | - Vanesa Bernal-Monterde
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (D.C.-D.); (S.E.); (E.M.F.-B.)
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (B.G.-R.); (A.S.-P.); (Y.G.-I.)
- Correspondence: (V.B.-M.); (J.M.A.-M.)
| | - Jose M. Arbones-Mainar
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; (B.G.-R.); (A.S.-P.); (Y.G.-I.)
- Translational Research Unit, Miguel Servet University Hospital, Instituto Aragonés de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain
- Centro de Investigación Biomédica en Red Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, 28029 Madrid, Spain
- Correspondence: (V.B.-M.); (J.M.A.-M.)
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Elsharkawy A, Samir R, El-Kassas M. Fibrosis regression following hepatitis C antiviral therapy. World J Hepatol 2022; 14:1120-1130. [PMID: 35978676 PMCID: PMC9258254 DOI: 10.4254/wjh.v14.i6.1120] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 04/16/2022] [Accepted: 05/12/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is one of the most common causes of liver pathology. It is a major etiological factor of continuous liver injury by triggering an uncontrolled inflammatory response, causing liver fibrosis and cirrhosis. Liver fibrosis is a dynamic process that can be reversible upon timely cessation of the injurious agent, which in cases of HCV is represented by the sustained virological response (SVR) following antiviral therapies. Direct-acting antiviral therapy has recently revolutionized HCV therapy and minimized complications. Liver fibrosis can be assessed with variable invasive and non-invasive methods, with certain limitations. Despite the broad validation of the diagnostic and prognostic value of non-invasive modalities of assessment of liver fibrosis in patients with HCV, the proper interpretation of liver stiffness measurement in patients after SVR remains unclear. It is also still a debate whether this regression is caused by the resolution of liver injury following treatment of HCV, rather than true fibrosis regression. Regression of liver fibrosis can possess a positive impact on patient's quality of life reducing the incidence of complications. However, fibrosis regression does not abolish the risk of developing hepatocellular carcinoma, which mandates regular screening of patients with advanced fibrosis.
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Affiliation(s)
- Aisha Elsharkawy
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
| | - Reham Samir
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt.
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30
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Salama II, Raslan HM, Abdel-Latif GA, Salama SI, Sami SM, Shaaban FA, Abdelmohsen AM, Fouad WA. Impact of direct-acting antiviral regimens on hepatic and extrahepatic manifestations of hepatitis C virus infection. World J Hepatol 2022; 14:1053-1073. [PMID: 35978668 PMCID: PMC9258264 DOI: 10.4254/wjh.v14.i6.1053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 04/01/2022] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a common cause of liver disease and is associated with various extrahepatic manifestations (EHMs). This mini-review outlines the currently available treatments for HCV infection and their prognostic effect on hepatic manifestations and EHMs. Direct-acting antiviral (DAA) regimens are considered pan-genotypic as they achieve a sustained virological response (SVR) > 85% after 12 wk through all the major HCV genotypes, with high percentages of SVR even in advanced fibrosis and cirrhosis. The risk factors for DAA failure include old males, cirrhosis, and the presence of resistance-associated substitutions (RAS) in the region targeted by the received DAAs. The effectiveness of DAA regimens is reduced in HCV genotype 3 with baseline RAS like A30K, Y93H, and P53del. Moreover, the European Association for the Study of the Liver recommended the identification of baseline RAS for HCV genotype 1a. The higher rate of hepatocellular carcinoma (HCC) after DAA therapy may be related to the fact that DAA regimens are offered to patients with advanced liver fibrosis and cirrhosis, where interferon was contraindicated to those patients. The change in the growth of pre-existing subclinical, undetectable HCC upon DAA treatment might be also a cause. Furthermore, after DAA therapy, the T cell-dependent immune response is much weaker upon HCV clearance, and the down-regulation of TNF-α or the elevated neutrophil to lymphocyte ratio might increase the risk of HCC. DAAs can result in reactivation of hepatitis B virus (HBV) in HCV co-infected patients. DAAs are effective in treating HCV-associated mixed cryoglobulinemia, with clinical and immunological responses, and have rapid and high effectiveness in thrombocytopenia. DAAs improve insulin resistance in 90% of patients, increase glomerular filtration rate, and decrease proteinuria, hematuria and articular manifestations. HCV clearance by DAAs allows a significant improvement in atherosclerosis and metabolic and immunological conditions, with a reduction of major cardiovascular events. They also improve physical function, fatigue, cognitive impairment, and quality of life. Early therapeutic approach with DAAs is recommended as it cure many of the EHMs that are still in a reversible stage and can prevent others that can develop due to delayed treatment.
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Affiliation(s)
- Iman Ibrahim Salama
- Department of Community Medicine Research, National Research Center, Giza 12622, Dokki, Egypt.
| | - Hala M Raslan
- Department of Internal Medicine, National Research Center, Giza 12622, Dokki, Egypt
| | - Ghada A Abdel-Latif
- Department of Community Medicine Research, National Research Center, Giza 12622, Dokki, Egypt
| | - Somaia I Salama
- Department of Community Medicine Research, National Research Center, Giza 12622, Dokki, Egypt
| | - Samia M Sami
- Department of Child Health, National Research Center, Giza 12622, Dokki, Egypt
| | - Fatma A Shaaban
- Department of Child Health, National Research Center, Giza 12622, Dokki, Egypt
| | - Aida M Abdelmohsen
- Department of Community Medicine Research, National Research Center, Giza 12622, Dokki, Egypt
| | - Walaa A Fouad
- Department of Community Medicine Research, National Research Center, Giza 12622, Dokki, Egypt
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Rojano-Toimil A, Rivera-Esteban J, Manzano-Nuñez R, Bañares J, Martinez Selva D, Gabriel-Medina P, Ferrer R, Pericàs JM, Ciudin A. When Sugar Reaches the Liver: Phenotypes of Patients with Diabetes and NAFLD. J Clin Med 2022; 11:jcm11123286. [PMID: 35743358 PMCID: PMC9225139 DOI: 10.3390/jcm11123286] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/03/2022] [Accepted: 06/06/2022] [Indexed: 01/27/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) have been traditionally linked to one another. Recent studies suggest that NAFLD may be increasingly common in other types of diabetes such as type 1 diabetes (T1DM) and less frequently ketone-prone and Maturity-onset Diabetes of the Young (MODY) diabetes. In this review, we address the relationship between hyperglycemia and insulin resistance and the onset and progression of NAFLD. In addition, despite the high rate of patients with T2DM and other diabetes phenotypes that can alter liver metabolism and consequently develop steatosis, fibrosis, and cirrhosis, NALFD screening is not still implemented in the daily care routine. Incorporating a clinical algorithm created around a simple, non-invasive, cost-effective model would identify high-risk patients. The principle behind managing these patients is to improve insulin resistance and hyperglycemia states with lifestyle changes, weight loss, and new drug therapies.
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Affiliation(s)
- Alba Rojano-Toimil
- Endocrinology Department, Vall d’Hebron University Hospital, 08035 Barcelona, Spain;
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
| | - Jesús Rivera-Esteban
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
- Medicine Department Bellaterra, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
| | - Ramiro Manzano-Nuñez
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
| | - Juan Bañares
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
| | - David Martinez Selva
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
- Spanish Network of Biomedical Research Centers, Diabetes and Metabolic Associated Disorders (CIBERdem), 28029 Madrid, Spain
| | - Pablo Gabriel-Medina
- Biochemistry Department, Vall d’Hebron University Hospital, 08035 Barcelona, Spain; (P.G.-M.); (R.F.)
- Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona (UAB), Bellaterra, 08193 Barcelona, Spain
| | - Roser Ferrer
- Biochemistry Department, Vall d’Hebron University Hospital, 08035 Barcelona, Spain; (P.G.-M.); (R.F.)
| | - Juan M Pericàs
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Spanish Network of Biomedical Research Centers, Liver and Digestive Diseases (CIBERehd), 28801 Madrid, Spain
- Correspondence: (J.M.P.); (A.C.)
| | - Andreea Ciudin
- Endocrinology Department, Vall d’Hebron University Hospital, 08035 Barcelona, Spain;
- Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (J.R.-E.); (R.M.-N.); (J.B.); (D.M.S.)
- Medicine Department Bellaterra, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
- Spanish Network of Biomedical Research Centers, Diabetes and Metabolic Associated Disorders (CIBERdem), 28029 Madrid, Spain
- Correspondence: (J.M.P.); (A.C.)
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Metabolic Dysfunction-Associated Fatty Liver Disease Is Associated with the Risk of Incident Cardiovascular Disease: A Prospective Cohort Study in Xinjiang. Nutrients 2022; 14:nu14122361. [PMID: 35745091 PMCID: PMC9231197 DOI: 10.3390/nu14122361] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 05/26/2022] [Accepted: 06/02/2022] [Indexed: 12/28/2022] Open
Abstract
In 2020, a group of international experts proposed a new term ‘metabolic dysfunction-associated fatty liver disease’ (MAFLD) to replace ‘non-alcoholic fatty liver disease’. This study aimed to describe the epidemic characteristics of MAFLD, incidence of cardiovascular disease (CVD), and relationship between MAFLD and incident CVD. In 2016, 12,794 Uyghur adults from Kashgar, Xinjiang, were grouped according to the presence or absence of MAFLD. The primary outcome was the occurrence of CVD events. Fatty liver was diagnosed using ultrasound. The prevalence of MAFLD was 16.55%. After excluding patients with previous CVD, 11,444 participants were followed up for a median period of 4.7 years. During the follow-up period, the overall CVD incidence was 10.40% (1190/11,444). The incidence of CVD in the patients with MAFLD was significantly higher than that in the non-MAFLD patients (18.38% vs. 9.02%, p < 0.001; multivariable-adjusted hazard ratio = 1.37, 95% CI = 1.20−1.56). The prevalence of MAFLD was relatively low, whereas the incidence of CVD was relatively high among the Uyghur adults in rural Xinjiang. Individuals with MAFLD have a higher risk of developing CVD independent of traditional cardiovascular risk factors, obesity, type 2 diabetes mellitus (T2DM), and dyslipidaemia.
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Genomic Relevance of FGFR2 on the Prognosis of HCV-Induced Hepatocellular Carcinoma Patients. J Clin Med 2022; 11:jcm11113093. [PMID: 35683481 PMCID: PMC9181427 DOI: 10.3390/jcm11113093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 05/25/2022] [Accepted: 05/27/2022] [Indexed: 12/24/2022] Open
Abstract
The Fibroblast Growth Factor Receptors (FGFRs) are known to regulate cancer metabolism in different tumor types, including hepatocellular carcinoma (HCC). Several risk factors are associated with HCC, of which viral infections (Hepatitis B and C) and cirrhosis are prominent. In Pakistan as well as in highly developed countries like the United States, hepatitis C virus HCV infections are most commonly reported in HCC. Here, we aimed to investigate the clinical relevance of FGFR receptors in HCC and their role in HCV-positive HCC cases. 264 HCC samples along with their clinical information and 96 normal liver samples were collected. qPCR was done to estimate the expression of FGFR1, FGFR2, FGFR3 and FGFR4. Three independent HCV-induced HCC cohorts (containing 293 HCC samples) were used for validation. According to in vitro results, FGFR1 was upregulated in HCV+ HCC patients. However, in all three independent cohorts of HCC, significant a down-regulation of FGFR1 was observed. FGFR2 overexpression was observed in the in vitro cohort as well as in three independent HCC cohorts. Interestingly, a strong correlation of FGFR2 expression was observed between cirrhosis and HCV in all four HCC cohorts. Our study suggested that FGFR2 expression can be used to classify HCC patients based on HCV infection. This FGFR2-based classification may lead to new therapeutic strategies against HCV-positive HCC subtypes.
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Triglyceride and Glucose Index as a Screening Tool for Nonalcoholic Liver Disease in Patients with Metabolic Syndrome. J Clin Med 2022; 11:jcm11113043. [PMID: 35683431 PMCID: PMC9181222 DOI: 10.3390/jcm11113043] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/18/2022] [Accepted: 05/25/2022] [Indexed: 02/04/2023] Open
Abstract
Background: Nonalcoholic fatty liver disease (NAFLD) is regarded as a component of metabolic syndrome, which involves insulin resistance (IR) as the primary physiopathological event. The aim of this study was to establish the association between IR, assessed using the triglyceride and glucose index (TyG), and histopathological features of NAFLD lesions. Methods: The study included 113 patients with metabolic syndrome. Fasting plasma glucose (FPG), fasting lipid profiles and liver enzymes were measured. IR was assessed by the TyG index. Liver biopsy was performed for assessment steatosis and fibrosis. Results: the TyG index had a mean value of 8.93 ± 1.45, with a higher value in the patients with overweight (p = 0.002) and obesity (p = 0.004) characteristics than in the patients with normal weight. The TyG index mean value was 8.78 ± 0.65 in subjects without NASH, 8.91 ± 0.57 in patients with borderline NASH and 9.13 ± 0.55 in patients with definite NASH. A significant difference was found between subjects without NASH and the ones with definite NASH (p = 0.004), as well as in patients with early fibrosis vs. those with significant fibrosis. The analysis of the area under the ROC curve proved that the TyG index is a predictor of NASH (p = 0.043). Conclusion: the TyG index is a facile tool that can be used to identify individuals at risk for NAFLD.
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Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome in Women: Effects of Lifestyle Modifications. J Clin Med 2022; 11:jcm11102759. [PMID: 35628889 PMCID: PMC9146022 DOI: 10.3390/jcm11102759] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/11/2022] [Accepted: 05/11/2022] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most widespread liver disease, characterized by fatty acids liver accumulation and subsequent fibrosis. NAFLD prevalence ranges from 80% to 90% in obese subjects and is estimated to be around 50% in patients with metabolic syndrome. In this clinical scenario, diet and lifestyle modifications can play an important role. There are several imaging techniques that can accurately diagnose fatty liver. Recently, ultrasound has acquired a leading role in the diagnosis and follow-up of fatty liver disease. Furthermore, elastosonography represents a valid alternative to liver biopsy. Shear wave elastosonography evaluates the elastic and mechanical properties of liver tissue. The aim is to evaluate the effects of lifestyle and nutritional interventions and a loss of body weight during hepatic steatosis through ultrasonographic and elastosonographic techniques. Thirty-two female subjects with metabolic syndrome were subjected to clinical, anthropometric, and laboratory assessments, as well as abdominal ultrasonographic/elastosonographic measurements taken from enrollment time (T0) and after 3 months (T1) of lifestyle modifications. After 3 months of lifestyle changes, significant weight loss was observed, with a marked improvement in all adiposity indices. The laboratory parameters at T1 showed significant decreases in total and LDL cholesterol, triglycerides, basal blood glucose, 120 min glycaemia, basal insulin and HOMA Index (p < 0.001). A similar improvement was observed at T1 for steatosis degree (p < 0.01) and elastosonographic measurements (Kpa p < 0.001). The linear regression analysis of the baseline conditions documented that the size of the liver positively correlated with body weight, BMI, neck and waist circumferences, waist to height ratio (WhtR), insulin and HOMA Index, fat mass and visceral fat, and steatosis grade. After 3 months, the liver size showed improvement with positive correlations to all previous variables. Hepatic stiffness (Kpa) positively correlated with neck circumference, visceral fat, and ALT, with basal insulin, gamma-GT, and AST, and with waist circumference, WhtR, and fat mass. The degree of steatosis was positively correlated with more variables and with greater statistical significance at T1 with respect to T0. Particularly, the positive correlations between the degree of steatosis and neck circumference (p < 0.001), HOMA Index, and triglycerides (p < 0.001) appeared to be very significant. NAFLD management in women with metabolic syndrome should be focused on lifestyle modifications. Moreover, liver involvement and improvement at follow-up could be evaluated in a non-invasive manner through ultrasonographic and elastosonographic techniques.
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Ciardullo S, Mantovani A, Ciaccio A, Carbone M, Invernizzi P, Perseghin G. Hepatitis C virus infection and diabetes: A complex bidirectional relationship. Diabetes Res Clin Pract 2022; 187:109870. [PMID: 35398458 DOI: 10.1016/j.diabres.2022.109870] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 03/22/2022] [Accepted: 04/04/2022] [Indexed: 11/03/2022]
Abstract
Chronic hepatitis C (CHC) and diabetes represent two severe chronic conditions responsible for a considerable number of deaths worldwide. They have a complex, bidirectional relationship. On the one hand, several cohort studies have shown that chronic HCV infection increases both the risk of developing diabetes in non-diabetic subjects (by inducing insulin resistance and promoting β-cell dysfunction) as well as the risk of developing macro and microvascular complications in patients with known diabetes; on the other hand, diabetes is an independent risk factor for liver-related events among patients with CHC, including a higher incidence of hepatocellular carcinoma, liver-related death and transplantation. Importantly, sustained virological response, which can be obtained in the vast majority of patients with the use of direct antiviral agents, does not only lead to a lower rate of liver-related outcomes, but also to improvements of glycemic control and reduction in the rate of complications among patients with diabetes. The aim of this review is to summarize available clinical evidence on the association among CHC, diabetes and related clinical outcomes. We will also briefly discuss the biological mechanisms underpinning the association between CHC and diabetes, as well as the implications this relationship should have on everyday clinical practice.
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Affiliation(s)
- Stefano Ciardullo
- Department of Medicine and Rehabilitation, Monza Policlinico di Monza, Monza, Italy; Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy.
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, University of Verona
| | - Antonio Ciaccio
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Marco Carbone
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Gianluca Perseghin
- Department of Medicine and Rehabilitation, Monza Policlinico di Monza, Monza, Italy; Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy
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Boonchai P, Kositamongkol C, Jitrukthai S, Phothirat S, Mepramoon E, Nimitpunya P, Srivanichakorn W, Chaisathaphol T, Washirasaksiri C, Auesomwang C, Sitasuwan T, Tinmanee R, Sayabovorn N, Charatcharoenwitthaya P, Phisalprapa P. Clinical Differences and Non-Alcoholic Fatty Liver Disease-Related Factors of Lean and Non-Lean Patients with Metabolic Syndrome. J Clin Med 2022; 11:jcm11092445. [PMID: 35566571 PMCID: PMC9103281 DOI: 10.3390/jcm11092445] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 04/19/2022] [Accepted: 04/24/2022] [Indexed: 12/10/2022] Open
Abstract
This study investigated differences in the clinical data and prevalence of lean and non-lean patients with non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). Data on patients with MetS who had results of ultrasonography or transient elastography were collected from a Thai university hospital database. Patients with exclusion criteria for NAFLD diagnosis were excluded. Patients’ clinical characteristic and the performances of three non-invasive scoring systems (fatty liver index [FLI], fibrosis-4 [FIB-4] index, and NAFLD fibrosis score [NFS]) were evaluated. The 743 subjects were classified into two groups: lean MetS (131 patients) and non-lean MetS (612 patients). The NAFLD prevalence in the non-lean group (62.6%) was higher than that in the lean group (31.3%). The age-adjusted odds ratio was 3.43. Advanced fibrosis was detected in 7.6% of lean patients and 10.8% of non-lean patients. FLI was not sensitive enough to detect NAFLD in the lean group at a high cutoff, but it performed acceptably at a low cutoff. FIB-4 performed better than NFS in determining advanced fibrosis. NAFLD was more common in non-lean than lean patients. Lean patients with MetS had a relatively higher risk of NAFLD than the general population. FLI and FIB-4 index performed acceptably in both groups.
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Affiliation(s)
- Punyisa Boonchai
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Chayanis Kositamongkol
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Suchanart Jitrukthai
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Sukumal Phothirat
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Euarat Mepramoon
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Pongpol Nimitpunya
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Weerachai Srivanichakorn
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Thanet Chaisathaphol
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Chaiwat Washirasaksiri
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Chonticha Auesomwang
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Tullaya Sitasuwan
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Rungsima Tinmanee
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Naruemit Sayabovorn
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;
| | - Pochamana Phisalprapa
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; (P.B.); (C.K.); (S.J.); (S.P.); (E.M.); (P.N.); (W.S.); (T.C.); (C.W.); (C.A.); (T.S.); (R.T.); (N.S.)
- Correspondence: ; Tel./Fax: +66-2-419-7190
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Nevola R, Messina V, Marrone A, Coppola N, Rescigno C, Esposito V, Sangiovanni V, Claar E, Pisaturo M, Fusco FM, Rosario P, Izzi A, Pisapia R, Rosato V, Maggi P, Adinolfi LE. Epidemiology of HCV and HBV in a High Endemic Area of Southern Italy: Opportunities from the COVID-19 Pandemic-Standardized National Screening or One Tailored to Local Epidemiology? BIOLOGY 2022; 11:609. [PMID: 35453808 PMCID: PMC9028790 DOI: 10.3390/biology11040609] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/13/2022] [Accepted: 04/14/2022] [Indexed: 12/16/2022]
Abstract
The COVID-19 pandemic led to the hospitalization of an unselected population with the possibility to evaluate the epidemiology of viral hepatitis. Thus, a retrospective multicenter study was conducted in an area of Southern Italy with the aim of assessing the prevalence of HCV and HBV markers and the ability of current screening program to capture cases. We evaluated 2126 hospitalized patients in seven COVID Centers of Naples and Caserta area in which 70% of the Campania population lives. HBsAg and HCV-Ab prevalence was 1.6% and 5.1%, respectively, with no differences between gender. Decade distribution for birth year shows a bimodal trend of HCV prevalence, with a peak (11.6%) in the decade 1930-1939 and a second peak (5.6%) for those born in 1960-1969. An analysis of the screening period imposed by the Italian government for those born between 1969 and 1989 shows that only 17% of cases of HCV infection could be captured. A small alignment of the screening period, i.e., those born from 1960 to 1984, would capture 40% of cases. The data confirm the high endemicity of our geographical area for hepatitis virus infections and underline the need for a tailored screening program according to the regional epidemiology.
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Affiliation(s)
- Riccardo Nevola
- Internal Medicine Unit, Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.M.); (L.E.A.)
- Hepatology Unit, Ospedale Evangelico Betania, 80147 Naples, Italy; (E.C.); (V.R.)
| | - Vincenzo Messina
- Infectious Diseases Unit, AORN Sant’Anna e San Sebastiano, 81100 Caserta, Italy; (V.M.); (P.M.)
| | - Aldo Marrone
- Internal Medicine Unit, Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.M.); (L.E.A.)
| | - Nicola Coppola
- Infectious Diseases Unit, Department of Mental Health and Public Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (N.C.); (M.P.)
| | - Carolina Rescigno
- Infectious Diseases and Neurology Unit, Cotugno Hospital, 80131 Naples, Italy; (C.R.); (A.I.); (R.P.)
| | - Vincenzo Esposito
- IVth Division of Immunodeficiency and Gender Infectious Diseases, Cotugno Hospital, 80131 Naples, Italy; (V.E.); (P.R.)
| | - Vincenzo Sangiovanni
- IIIrd Infectious Diseases Unit, Cotugno Hospital, 80131 Naples, Italy; (V.S.); (F.M.F.)
| | - Ernesto Claar
- Hepatology Unit, Ospedale Evangelico Betania, 80147 Naples, Italy; (E.C.); (V.R.)
| | - Mariantonietta Pisaturo
- Infectious Diseases Unit, Department of Mental Health and Public Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (N.C.); (M.P.)
| | - Francesco Maria Fusco
- IIIrd Infectious Diseases Unit, Cotugno Hospital, 80131 Naples, Italy; (V.S.); (F.M.F.)
| | - Pietro Rosario
- IVth Division of Immunodeficiency and Gender Infectious Diseases, Cotugno Hospital, 80131 Naples, Italy; (V.E.); (P.R.)
| | - Antonio Izzi
- Infectious Diseases and Neurology Unit, Cotugno Hospital, 80131 Naples, Italy; (C.R.); (A.I.); (R.P.)
| | - Raffaella Pisapia
- Infectious Diseases and Neurology Unit, Cotugno Hospital, 80131 Naples, Italy; (C.R.); (A.I.); (R.P.)
| | - Valerio Rosato
- Hepatology Unit, Ospedale Evangelico Betania, 80147 Naples, Italy; (E.C.); (V.R.)
| | - Paolo Maggi
- Infectious Diseases Unit, AORN Sant’Anna e San Sebastiano, 81100 Caserta, Italy; (V.M.); (P.M.)
| | - Luigi Elio Adinolfi
- Internal Medicine Unit, Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (A.M.); (L.E.A.)
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Schmid A, Arians M, Karrasch T, Pons-Kühnemann J, Schäffler A, Roderfeld M, Roeb E. Improvement of Type 2 Diabetes Mellitus and Attenuation of NAFLD Are Associated with the Success of Obesity Therapy. J Clin Med 2022; 11:jcm11071756. [PMID: 35407364 PMCID: PMC8999703 DOI: 10.3390/jcm11071756] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 03/16/2022] [Indexed: 12/13/2022] Open
Abstract
Obesity and type 2 diabetes mellitus (T2D) represent important comorbidities of the metabolic syndrome, which are associated with non-alcoholic fatty liver disease (NAFLD)-related hepatic fibrosis. In total, 160 morbidly obese patients-81 following a low-calorie formula diet (LCD) program and 79 undergoing bariatric surgery (Roux-en-Y gastric bypass, RYGB)-were examined for anthropometric and metabolic parameters at base-line and during 12 months of weight loss, focusing on a putative co-regulation of T2D parameters and liver fibrosis risk. High NAFLD fibrosis scores (NFS) before intervention were associated with elevated HbA1c levels and T2D. Loss of weight and body fat percentage (BFL) were associated with improved glucose and lipid metabolism and reduced risk of NAFLD-related fibrosis, with particularly beneficial effects by RYGB. Both T2D improvement and NFS decrease were positively associated with high BFL. A highly significant correlation of NFS reduction with BFL was restricted to male patients while being absent in females, accompanied by generally higher BFL in men. Overall, the data display the relation of BFL, T2D improvement, and reduced NAFLD-related fibrosis risk during weight loss in morbidly obese individuals induced by diet or RYGB. Furthermore, our data suggest a considerable sexual dimorphism concerning the correlation of fat loss and improved risk of liver fibrosis.
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Affiliation(s)
- Andreas Schmid
- Department of Internal Medicine III, Justus Liebig University, 35392 Giessen, Germany; (A.S.); (T.K.); (A.S.)
| | - Miriam Arians
- Department of Gastroenterology, Internal Medicine II, Justus Liebig University, Klinikstr. 33, 35392 Giessen, Germany; (M.A.); (M.R.)
| | - Thomas Karrasch
- Department of Internal Medicine III, Justus Liebig University, 35392 Giessen, Germany; (A.S.); (T.K.); (A.S.)
| | - Jörn Pons-Kühnemann
- Institute of Medical Informatics, Justus Liebig University, 35392 Giessen, Germany;
| | - Andreas Schäffler
- Department of Internal Medicine III, Justus Liebig University, 35392 Giessen, Germany; (A.S.); (T.K.); (A.S.)
| | - Martin Roderfeld
- Department of Gastroenterology, Internal Medicine II, Justus Liebig University, Klinikstr. 33, 35392 Giessen, Germany; (M.A.); (M.R.)
| | - Elke Roeb
- Department of Gastroenterology, Internal Medicine II, Justus Liebig University, Klinikstr. 33, 35392 Giessen, Germany; (M.A.); (M.R.)
- Correspondence:
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The Coexistence of Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus. J Clin Med 2022; 11:jcm11051375. [PMID: 35268466 PMCID: PMC8910939 DOI: 10.3390/jcm11051375] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/28/2022] [Accepted: 03/01/2022] [Indexed: 12/12/2022] Open
Abstract
The incidence of nonalcoholic fatty liver disease (NAFLD) is growing worldwide. Epidemiological data suggest a strong relationship between NAFLD and T2DM. This is associated with common risk factors and pathogenesis, where obesity, insulin resistance and dyslipidemia play pivotal roles. Expanding knowledge on the coexistence of NAFLD and T2DM could not only protect against liver damage and glucotoxicity, but may also theoretically prevent the subsequent occurrence of other diseases, such as cancer and cardiovascular disorders, as well as influence morbidity and mortality rates. In everyday clinical practice, underestimation of this problem is still observed. NAFLD is not looked for in T2DM patients; on the contrary, diagnosis for glucose metabolism disturbances is usually not performed in patients with NAFLD. However, simple and cost-effective methods of detection of fatty liver in T2DM patients are still needed, especially in outpatient settings. The treatment of NAFLD, especially where it coexists with T2DM, consists mainly of lifestyle modification. It is also suggested that some drugs, including hypoglycemic agents, may be used to treat NAFLD. Therefore, the aim of this review is to detail current knowledge of NAFLD and T2DM comorbidity, its prevalence, common pathogenesis, diagnostic procedures, complications and treatment, with special attention to outpatient clinics.
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Brodosi L, Petta S, Petroni ML, Marchesini G, Morelli MC. Management of Diabetes in Candidates for Liver Transplantation and in Transplant Recipients. Transplantation 2022; 106:462-478. [PMID: 34172646 PMCID: PMC9904447 DOI: 10.1097/tp.0000000000003867] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 05/31/2021] [Accepted: 06/02/2021] [Indexed: 11/25/2022]
Abstract
Diabetes is common in patients waitlisted for liver transplantation because of end-stage liver disease or hepatocellular cancer as well as in posttransplant phase (posttransplantation diabetes mellitus). In both conditions, the presence of diabetes severely affects disease burden and long-term clinical outcomes; careful monitoring and appropriate treatment are pivotal to reduce cardiovascular events and graft and recipients' death. We thoroughly reviewed the epidemiology of diabetes in the transplant setting and the different therapeutic options, from lifestyle intervention to antidiabetic drug use-including the most recent drug classes available-and to the inclusion of bariatric surgery in the treatment cascade. In waitlisted patients, the old paradigm that insulin should be the treatment of choice in the presence of severe liver dysfunction is no longer valid; novel antidiabetic agents may provide adequate glucose control without the risk of hypoglycemia, also offering cardiovascular protection. The same evidence applies to the posttransplant phase, where oral or injectable noninsulin agents should be considered to treat patients to target, limiting the impact of disease on daily living, without interaction with immunosuppressive regimens. The increasing prevalence of liver disease of metabolic origin (nonalcoholic fatty liver) among liver transplant candidates, also having a higher risk of noncirrhotic hepatocellular cancer, is likely to accelerate the acceptance of new drugs and invasive procedures, as suggested by international guidelines. Intensive lifestyle intervention programs remain however mandatory, both before and after transplantation. Achievement of adequate control is mandatory to increase candidacy, to prevent delisting, and to improve long-term outcomes.
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Affiliation(s)
- Lucia Brodosi
- IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater University, Bologna, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Maria L. Petroni
- IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater University, Bologna, Italy
| | - Giulio Marchesini
- IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater University, Bologna, Italy
| | - Maria C. Morelli
- IRCCS – Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Meritsi A, Manesis E, Koussis P, Rapti S, Latsou D, Tsitsopoulos E, Moshoyianni H, Manolakopoulos S, Pektasides D, Thanopoulou A. PNPLA3 rs 738409 and Other Nongenetic Factors Associated with Hepatic Steatosis Estimated by Magnetic Resonance Imaging Proton Density Fat Fraction in Adult Greek Subjects with Type 2 Diabetes Mellitus. Metab Syndr Relat Disord 2022; 20:124-131. [PMID: 34962148 DOI: 10.1089/met.2021.0098] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Objectives: Nonalcoholic fatty liver disease is dramatically increasing in parallel with the pandemic of type 2 diabetes mellitus. We investigated factors associated with hepatic steatosis (HS) in adult Greek individuals with established type 2 diabetes mellitus. Materials and Methods: We investigated 120 consecutive people with type 2 diabetes attending the Diabetic Outpatient Clinic at an Academic Hospital in Athens, Greece. All of them had demographic, clinical, and biochemical data recorded. HS was estimated by magnetic resonance imaging determined by proton density fat fraction software and defined as the percentage of total liver fat divided by the liver volume. HS of >5% was considered abnormal. The PNPLA3 (I148M) variant was evaluated as a genetic factor by standard molecular techniques. FibroMax™ was also calculated. Results: Of the 120 participants, median age was 61.7, 46% were females, diabetes duration was 10 years, and HbA1c (glycated hemoglobin) was 6.7%. The median value of HS was 7.8. The PNPLA3 rs738409 CC/CG/GG genotype frequencies were 54.2%, 35%, and 10.8%, respectively. In multivariate analysis, PNPLA3 rs738409 (β = 0.425, P = 0.001), waist circumference (β = 2.448, P = 0.001), and female sex (β = 0.419, P = 0.002) had a direct association with HS, while duration of diabetes (β = -0.179, P = 0.011) had an inverse association with HS. Conclusions: HS in type 2 diabetes is the sum of interplay of various factors exerting a direct or an inverse association, the most prominent among them being abdominal obesity and PNPLA3 molecular variability.
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Affiliation(s)
- Angeliki Meritsi
- Diabetic Center, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | | | - Stamatia Rapti
- Laboratory of Molecular Genetics, Biomedicine SA, Athens, Greece
| | - Dimitra Latsou
- Department of Social and Educational Policy, University of Peloponnese, Corinth, Greece
| | | | | | - Spilios Manolakopoulos
- Liver & Gastrointestinal Unit, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Pektasides
- 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Thanopoulou
- Diabetic Center, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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HCV Genotype Has No Influence on the Incidence of Diabetes-EpiTer Multicentre Study. J Clin Med 2022; 11:jcm11020379. [PMID: 35054072 PMCID: PMC8780546 DOI: 10.3390/jcm11020379] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 12/30/2021] [Accepted: 01/05/2022] [Indexed: 12/17/2022] Open
Abstract
HCV infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, one finds more and more extrahepatic manifestations of HCV infection, including its possible influence on the development of diabetes. In the presented work, one finds the frequency analysis of the incidence of diabetes among 2898 HCV infected patients treated in Poland, and the assessment of their relevance to the HCV genotype and the progression of fibrosis. The results indicate that the hepatitis C infection seems to be a risk factor for diabetes in persons with more advanced liver fibrosis, for older people, and for the male gender. Thus, one found no differences regarding the frequency of its incidence depending on HCV genotype, including genotype 3.
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Xing Y, Chen J, Liu J, Song G, Ma H. Relationship Between Serum Uric Acid-to-Creatinine Ratio and the Risk of Metabolic-Associated Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes 2022; 15:257-267. [PMID: 35140486 PMCID: PMC8818775 DOI: 10.2147/dmso.s350468] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 01/19/2022] [Indexed: 11/23/2022] Open
Abstract
PURPOSE To investigate the association between serum uric acid-to-creatinine ratio (SUA/Cr) and the risk of developing metabolic-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS Overall, 1434 patients with T2DM who were admitted to Hebei General Hospital from January 2019 to December 2019 were selected as the study subjects. According to abdominal ultrasound findings, patients were divided into two groups: MAFLD group and non-MAFLD group. A total of 734 patients were diagnosed with MAFLD. Participants were divided into three study groups according to the SUA/Cr ratio. Chi-square test and one-way analysis of variance were used to perform a comparison between groups. The relationship between SUA/Cr ratio and MAFLD risk was analyzed using correlation analysis and regression analysis. Furthermore, subgroup analyses were performed to verify the robustness of the results. RESULTS The detection rate of MAFLD in patients with T2DM was 51.2%, and the detection rate of progressive liver fibrosis in T2DM patients with MAFLD was 36.6%. A significantly higher SUA/Cr ratio was seen in the MAFLD group than in the non-MAFLD group. After adjusting for confounding factors, multivariate logistic regression analysis revealed that the SUA/Cr ratio was an independent risk factor for MAFLD development. Stronger correlations were found in participants with a body mass index ranging between 23 and 28 kg/m2, HbA1C >7%, or female sex. CONCLUSION An elevated SUA/Cr index is independently correlated with an increased risk of MAFLD in Chinese adults with T2DM.
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Affiliation(s)
- Yuling Xing
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China
- Graduate School of Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China
| | - Jinhu Chen
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China
- Graduate School of Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China
| | - Jing Liu
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China
- Graduate School of Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China
| | - Guangyao Song
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China
| | - Huijuan Ma
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China
- Correspondence: Huijuan Ma, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China, Tel +86 18032838686, Email
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Drożdż K, Nabrdalik K, Hajzler W, Kwiendacz H, Gumprecht J, Lip GYH. Metabolic-Associated Fatty Liver Disease (MAFLD), Diabetes, and Cardiovascular Disease: Associations with Fructose Metabolism and Gut Microbiota. Nutrients 2021; 14:103. [PMID: 35010976 PMCID: PMC8746577 DOI: 10.3390/nu14010103] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 12/23/2021] [Accepted: 12/23/2021] [Indexed: 12/13/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition associated with type 2 diabetes (T2DM) and cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies NAFLD, the current nomenclature has been revised, and the term metabolic-associated fatty liver disease (MAFLD) has been proposed. The new definition emphasizes the bidirectional relationships and increases awareness in looking for fatty liver disease among patients with T2DM and CVD or its risk factors, as well as looking for these diseases among patients with NAFLD. The most recommended treatment method of NAFLD is lifestyle changes, including dietary fructose limitation, although other treatment methods of NAFLD have recently emerged and are being studied. Given the focus on the liver-gut axis targeting, bacteria may also be a future aim of NAFLD treatment given the microbiome signatures discriminating healthy individuals from those with NAFLD. In this review article, we will provide an overview of the associations of fructose consumption, gut microbiota, diabetes, and CVD in patients with NAFLD.
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Affiliation(s)
- Karolina Drożdż
- Department of Internal Medicine, Diabetology and Nephrology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (K.D.); (H.K.); (J.G.); (G.Y.H.L.)
| | - Katarzyna Nabrdalik
- Department of Internal Medicine, Diabetology and Nephrology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (K.D.); (H.K.); (J.G.); (G.Y.H.L.)
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool L14 3PE, UK
| | - Weronika Hajzler
- Doctoral School, Department of Pediatric Hematology and Oncology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland;
| | - Hanna Kwiendacz
- Department of Internal Medicine, Diabetology and Nephrology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (K.D.); (H.K.); (J.G.); (G.Y.H.L.)
| | - Janusz Gumprecht
- Department of Internal Medicine, Diabetology and Nephrology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (K.D.); (H.K.); (J.G.); (G.Y.H.L.)
| | - Gregory Y. H. Lip
- Department of Internal Medicine, Diabetology and Nephrology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (K.D.); (H.K.); (J.G.); (G.Y.H.L.)
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool L14 3PE, UK
- Department of Clinical Medicine, Aalborg University, 9100 Aalborg, Denmark
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Zhang C, Liu S, Yang M. Hepatocellular Carcinoma and Obesity, Type 2 Diabetes Mellitus, Cardiovascular Disease: Causing Factors, Molecular Links, and Treatment Options. Front Endocrinol (Lausanne) 2021; 12:808526. [PMID: 35002979 PMCID: PMC8733382 DOI: 10.3389/fendo.2021.808526] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 12/07/2021] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which will affect more than a million people by the year 2025. However, current treatment options have limited benefits. Nonalcoholic fatty liver disease (NAFLD) is the fastest growing factor that causes HCC in western countries, including the United States. In addition, NAFLD co-morbidities including obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVDs) promote HCC development. Alteration of metabolites and inflammation in the tumor microenvironment plays a pivotal role in HCC progression. However, the underlying molecular mechanisms are still not totally clear. Herein, in this review, we explored the latest molecules that are involved in obesity, T2DM, and CVDs-mediated progression of HCC, as they share some common pathologic features. Meanwhile, several therapeutic options by targeting these key factors and molecules were discussed for HCC treatment. Overall, obesity, T2DM, and CVDs as chronic metabolic disease factors are tightly implicated in the development of HCC and its progression. Molecules and factors involved in these NAFLD comorbidities are potential therapeutic targets for HCC treatment.
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Affiliation(s)
- Chunye Zhang
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, United States
| | - Shuai Liu
- The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO, United States
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48
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The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2021; 22:ijms222413219. [PMID: 34948020 PMCID: PMC8704688 DOI: 10.3390/ijms222413219] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/25/2021] [Accepted: 12/02/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut microbiota, and interaction between the brain-liver-axis and the regulation of hepatic lipid metabolism. The new therapeutic approaches in the treatment of NAFLD are targeting some of these milestones along the pathophysiological pathway and include drugs like agonists of peroxisome proliferator-activated receptors (PPARs), glucagon-like peptide-1 (GLP-1) agonists, sodium/glucose transport protein 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists, probiotics, and symbiotics. Further efforts in biomedical sciences should focus on the investigation of the relationship between the microbiome, liver metabolism, and response to inflammation, systemic consequences of metabolic syndrome.
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Role and Treatment of Insulin Resistance in Patients with Chronic Kidney Disease: A Review. Nutrients 2021; 13:nu13124349. [PMID: 34959901 PMCID: PMC8707041 DOI: 10.3390/nu13124349] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 11/26/2021] [Accepted: 11/30/2021] [Indexed: 01/11/2023] Open
Abstract
Patients with chronic kidney disease (CKD) and dialysis have higher mortality than those without, and cardiovascular disease (CVD) is the main cause of death. As CVD is caused by several mechanisms, insulin resistance plays an important role in CVD. This review summarizes the importance and mechanism of insulin resistance in CKD and discusses the current evidence regarding insulin resistance in patients with CKD and dialysis. Insulin resistance has been reported to influence endothelial dysfunction, plaque formation, hypertension, and dyslipidemia. A recent study also reported an association between insulin resistance and cognitive dysfunction, non-alcoholic fatty liver disease, polycystic ovary syndrome, and malignancy. Insulin resistance increases as renal function decrease in patients with CKD and dialysis. Several mechanisms increase insulin resistance in patients with CKD, such as chronic inflammation, oxidative stress, obesity, and mineral bone disorder. There is the possibility that insulin resistance is the potential future target of treatment in patients with CKD.
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50
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Su PY, Chen YY, Lai JH, Chen HM, Yao CT, Liu IL, Zeng YH, Huang SP, Hsu YC, Wu SS, Siao FY, Yen HH. Real-World Experience of Chronic Hepatitis C-Related Compensated Liver Cirrhosis Treated with Glecaprevir/Pibrentasvir: A Multicenter Retrospective Study. J Clin Med 2021; 10:jcm10225236. [PMID: 34830518 PMCID: PMC8619604 DOI: 10.3390/jcm10225236] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 11/05/2021] [Accepted: 11/09/2021] [Indexed: 12/18/2022] Open
Abstract
Background: Glecaprevir/pibrentasvir is a protease inhibitor-containing pangenotypic direct-acting antiviral regimen that has been approved for the treatment of chronic hepatitis C. The present study aimed to evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients with compensated cirrhosis in a real-world setting. Methods: We evaluated the real-world safety and efficacy of glecaprevir/pibrentasvir in patients with compensated cirrhosis from five hospitals in the Changhua Christian Care System, who underwent treatment between August 2018 and October 2020. The primary endpoint was a sustained virological response observed 12 weeks after completion of the treatment. Results: Ninety patients, including 70 patients who received the 12-week therapy and 20 patients who received the 8-week therapy, were enrolled. The mean age of the patients was 65 years, and 57.8% of the patients were males. Sixteen (17.8%) patients had end-stage renal disease, and 15 (16.7%) had co-existing hepatoma. The hepatitis C virus genotypes 1 (40%) and 2 (35.6%) were most common. The common side effects included anorexia (12.2%), pruritus (7.8%), abdominal discomfort (7.8%), and malaise (7.8%). Laboratory adverse grade ≥3 events included anemia (6.3%), thrombocytopenia (5.1%), and jaundice (2.2%). The overall sustained virological response rates were 94.4% and 97.7% in the intention-to-treat and per-protocol analyses, respectively. Conclusions: the glecaprevir/pibrentasvir treatment regimen was highly effective and well tolerated among patients with compensated cirrhosis in the real-world setting.
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Affiliation(s)
- Pei-Yuan Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Yang-Yuan Chen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
- Division of Gastroenterology, Department of Internal Medicine, Yuanlin Christian Hospital, Changhua 500, Taiwan
- Department of Hospitality, MingDao University, Changhua 500, Taiwan
| | - Jun-Hung Lai
- Division of Gastroenterology, Department of Internal Medicine, Erhlin Christian Hospital, Changhua 500, Taiwan;
| | - Hung-Ming Chen
- Division of Gastroenterology, Department of Internal Medicine, Yunlin Christian Hospital, Yunlin 648, Taiwan;
| | - Chih-Ta Yao
- Division of Gastroenterology, Department of Internal Medicine, Lukang Christian Hospital, Changhua 500, Taiwan;
| | - I-Ling Liu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Ya-Huei Zeng
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Siou-Ping Huang
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Yu-Chun Hsu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Shun-Sheng Wu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Fu-Yuan Siao
- Department of Emergency Medicine, Changhua Christian Hospital, Changhua 500, Taiwan;
- Department of Kinesiology, Health and Leisure, Chienkuo Technology University, Changhua 500, Taiwan
| | - Hsu-Heng Yen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
- Artificial Intelligence Development Center, Changhua Christian Hospital, Changhua 500, Taiwan
- General Education Center, Chienkuo Technology University, Changhua 500, Taiwan
- Department of Electrical Engineering, Chung Yuan University, Taoyuan 320, Taiwan
- College of Medicine, National Chung Hsing University, Taichung 400, Taiwan
- Correspondence: ; Tel.: +886-4-723-8595-5501
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