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Grancini V, Cogliati I, Alicandro G, Gaglio A, Gatti S, Donato MF, Orsi E, Resi V. Assessment of hepatic fibrosis with non-invasive indices in subjects with diabetes before and after liver transplantation. Front Endocrinol (Lausanne) 2024; 15:1359960. [PMID: 38505744 PMCID: PMC10948411 DOI: 10.3389/fendo.2024.1359960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 02/21/2024] [Indexed: 03/21/2024] Open
Abstract
Introduction One of the most common complications of cirrhosis is diabetes, which prevalence is strictly related to severity of hepatopathy. Actually, there are no data on the persistence of post-transplant glucose abnormalities and on a potential impact of diabetes on development of fibrosis in the transplanted liver. To this aim, we evaluated liver fibrosis in cirrhotic subjects before and after being transplanted. Methods The study included 111 individuals who had liver transplantation. The assessment was performed before and two years after surgery to investigate a potential impact of the persistence of diabetes on developing de novo fibrosis in the transplanted liver. The degree of fibrosis was assessed using the Fibrosis Index Based on 4 Factors (FIB-4) and the Aspartate to Platelet Ratio Index (APRI). Results At pre-transplant evaluation, 63 out of 111 (56.8%) subjects were diabetic. Diabetic subjects had higher FIB-4 (Geometric mean, 95% confidence interval: 9.74, 8.32-11.41 vs 5.93, 4.71-7.46, P<0.001) and APRI (2.04, 1.69-2.47 vs 1.18, 0.90-1.55, P<0.001) compared to non-diabetic subjects. Two years after transplantation, 39 out of 111 (35.1%) subjects remained with diabetes and continued to show significantly higher FIB-4 (3.14, 2.57-3.82 vs 1.87, 1.55-2.27, P<0.001) and APRI (0.52, 0.39-0.69 vs 0.26, 0.21-0.32, P<0.001) compared to subjects without diabetes. Discussion Thus, persistence of diabetes after surgery is a possible risk factor for an evolution to fibrosis in the transplanted liver, potentially leading to worsened long-term outcomes in this population.
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Affiliation(s)
- Valeria Grancini
- Endocrinology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Irene Cogliati
- Endocrinology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Gianfranco Alicandro
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Department of Pediatrics, Cystic Fibrosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Alessia Gaglio
- Endocrinology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Stefano Gatti
- Center for Preclinical Research, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - Maria Francesca Donato
- Hepatology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Emanuela Orsi
- Endocrinology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Veronica Resi
- Endocrinology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
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Du Y, Khera T, Liu Z, Tudrujek-Zdunek M, Dworzanska A, Cornberg M, Xu CJ, Tomasiewicz K, Wedemeyer H. Controlled Attenuation Parameter Is Associated with a Distinct Systemic Inflammatory Milieu after Clearance of HCV Infection. Biomedicines 2023; 11:1529. [PMID: 37371624 DOI: 10.3390/biomedicines11061529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 05/15/2023] [Accepted: 05/17/2023] [Indexed: 06/29/2023] Open
Abstract
Hepatitis C virus (HCV) infection is closely associated with lipid metabolism defects along with a high prevalence of hepatic steatosis. After HCV clearance, steatosis persists in many patients. However, the reasons behind this phenomenon are not completely clear. To investigate the association between 92 soluble inflammatory mediators (SIMs) and the steatosis grade, we made use of a cohort of 94 patients with chronic HCV infection who cleared HCV after direct-acting antiviral agent (DAA) treatment. Patients were classified into three groups according to their controlled attenuation parameter (CAP). CAP is associated with ALT, γ-GT and liver stiffness after HCV clearance. While stem cell factor (SCF) and tumor necrosis factor ligand superfamily member 12 (TWEAK) levels were significantly reduced in patients with CAP > 299 dB/m, the levels of fibroblast growth factor (FGF)-21 and interleukin-18 receptor 1 (IL-18R1) were higher in those patients at week 96 after virus clearance. These four markers also showed a linear correlation with CAP values. FGF-21 levels correlated with CAP only after HCV clearance. Taken together, these four biomarkers, namely SCF, TWEAK, FGF-21 and IL-18R1, are associated with CAP status after virus clearance. A potential role of these proteins in the pathogenesis of post-sustained viral response (SVR) nonalcoholic steatohepatitis requires further investigation.
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Affiliation(s)
- Yanqin Du
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
- Department of Infectious Diseases, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Tanvi Khera
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- International AIDS Vaccine Initiative (IAVI), 122002 Gurugram, Haryana, India
| | - Zhaoli Liu
- Centre for Individualized Infection Medicine (CiiM), a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), 30625 Hannover, Germany
- TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany
| | | | - Anna Dworzanska
- Department of Infectious Diseases, Medical University of Lublin, 20-081 Lublin, Poland
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany
| | - Cheng-Jian Xu
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- Centre for Individualized Infection Medicine (CiiM), a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), 30625 Hannover, Germany
- TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases, Medical University of Lublin, 20-081 Lublin, Poland
| | - Heiner Wedemeyer
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- Excellence Cluster Resist, Hannover Medical School, 30625 Hannover, Germany
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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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Ansari RM, Baker P. Identifying the predictors of Covid-19 infection outcomes and development of prediction models. J Infect Public Health 2021; 14:751-756. [PMID: 34022732 PMCID: PMC7970794 DOI: 10.1016/j.jiph.2021.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/15/2021] [Accepted: 03/14/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND The infection of Corona Virus Disease (Covid-19) is challenging health problems worldwide. COVID-19 pandemic is spreading all over the world with the number of infected cases increased to 54.4 million with 1.32 million deaths. Different types of statistical models have been developed to predict viral infection and multiple studies have compared the performance of these predictive models, but results were not consistent. This study aimed to develop and provide easy to use model to predict the Covid-19 infection severity in the patients and to help understanding the patient's condition. METHODS This study analyzed simulated data obtained from the large database for 340 patients with an active Covid-19 infection. The study identified predictors of Covid-19 outcomes that may be measured in two different ways: the total T-cell levels in the blood with T-cell subsets and number of cells in the blood infected with virus. All measures are relatively unobtrusive as they only require a blood sample, however there is a significant laboratory cost implications for measuring the number of cells infected with virus. This study used methodological approach using two different methods showing how multiple regression and logistic regression can be used in the context of Covid-19 longitudinal data to develop the prediction models. RESULTS This study has identified the predictors of Covid-19 infection outcomes and developed prediction models. In the regression model of Total_T Cell, the predictors BMI, comorbidity and Total_Tcell were all associated with increased levels of infection severity (p < 0.001). For BMI, the mean % of unhealthy cells increased by 0.42 (95% CI 0.24 to 0.60) and comorbidity predictor has on average 8.3% more unhealthy liver cells than without comorbidity (95% CI - 2.9%-1.29%). The results of multivariate logistic regression model predicting the Covid-19 Infection severity were promising. The significant predictors were observed such as Age (OR 0.95, p = 0.02, 95% CI: 0.91-0.99), Helper T_cells (OR O.93, p = 0.03, 95% CI: 0.87-0.99), Basic_Tcell (OR 1.11, p = 0.001, 95% CI: 1.06-1.71) and Comorbidity (OR 0.41, p = 0.05, 95% CI: 0.16-1.07). CONCLUSIONS In this study recommendation has been provided to clinical researchers on the best way to use the various Covid-19 infections measures along with identifying other possible predictors of Covid-19 infection. It is imperative to monitor closely the T-cell subsets using prediction models that might provide valuable information about the patient's condition during the treatment process.
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Affiliation(s)
- Rashid M Ansari
- School of Public Health, Faculty of Medicine, The University of Queensland, Australia.
| | - Peter Baker
- Senior Lecturer, Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, The University of Queensland, Australia.
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Chang ML, Yang Z, Yang SS. Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression. Int J Mol Sci 2020; 21:E8308. [PMID: 33167521 PMCID: PMC7663948 DOI: 10.3390/ijms21218308] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 10/30/2020] [Accepted: 11/01/2020] [Indexed: 12/13/2022] Open
Abstract
Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related to low-grade systemic inflammation characterized by altered adipokine regulation. Obesity-related digestive diseases, including gastroesophageal reflux disease, Barrett's esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, viral hepatitis-related diseases, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes, might cause specific alterations in adipokine profiles. These patterns and associated bases potentially contribute to the identification of prognostic biomarkers and therapeutic approaches for the associated digestive diseases. This review highlights important findings about altered adipokine profiles relevant to digestive diseases, including hepatic, pancreatic, gastrointestinal, and biliary tract diseases, with a perspective on clinical implications and mechanistic explorations.
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Affiliation(s)
- Ming-Ling Chang
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Zinger Yang
- Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA;
| | - Sien-Sing Yang
- Liver Center, Cathay General Hospital Medical Center, Taipei 10630, Taiwan;
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Chung W, Promrat K, Wands J. Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases. World J Hepatol 2020; 12:533-557. [PMID: 33033564 PMCID: PMC7522556 DOI: 10.4254/wjh.v12.i9.533] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/03/2020] [Accepted: 08/15/2020] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) negatively affects the development and progression of chronic liver diseases (CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma (HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.
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Affiliation(s)
- Waihong Chung
- Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, Providence, RI 02905, United States.
| | - Kittichai Promrat
- Division of Gastroenterology and Hepatology, Providence VA Medical Center, Providence, RI 02908, United States
| | - Jack Wands
- Liver Research Center, The Warren Alpert Medical School of Brown University, Providence, RI 02903, United States
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Cunha GM, Correa de Mello LL, Hasenstab KA, Spina L, Bussade I, Prata Mesiano JM, Coutinho W, Guzman G, Sajoux I. MRI estimated changes in visceral adipose tissue and liver fat fraction in patients with obesity during a very low-calorie-ketogenic diet compared to a standard low-calorie diet. Clin Radiol 2020; 75:526-532. [PMID: 32204895 DOI: 10.1016/j.crad.2020.02.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 02/20/2020] [Indexed: 02/07/2023]
Abstract
AIM To compare the changes in visceral adipose tissue (VAT), liver fat fraction, and liver stiffness using quantitative magnetic resonance imaging (MRI) during a very-low-calorie ketogenic (VLCK) diet and a standard low-calorie diet (LC). MATERIALS AND METHODS The study involved secondary analysis of prospective collected clinical data. Patients undergoing weight loss interventions were randomised to either a LC or a VLCK diet. VAT, liver fat fraction, and stiffness were measured at baseline and after 2 months. RESULTS Forty-six patients were included; 39 patients were evaluated at baseline and at 2 months follow-up. Mean weight loss was -9.7±3.8 kg (interquartile range [IQR]: -12.3; -7 kg) in the VLCK group and -1.67±2.2 kg (IQR: -3.3, -0.1 kg) in the LC group (p<0.0001). Mean VAT reductions were -39.3±40 cm2 (IQR: -52, -10 cm2) and -12.5±38.3 cm2 (IQR: -29, 5 cm2; p=0.0398), and mean liver proton density fat fraction (PDFF) reductions were -4.77±4.2% (IQR: -7.3, -1.7%) and -0.79±1.7%, (IQR: -1.8, -0.4%; p<0.005) in the VLCK group and in the LC group, respectively. No significant changes in liver stiffness occurred from baseline to follow-up. CONCLUSION A VLCK diet resulted in greater weight loss than a standard low-calorie diet and in significantly greater reduction in liver PDFF. As anthropometric measurements may not correlate with liver fat changes, it may be advantageous to include quantitative MRI to the monitoring strategies of patients undergoing weight-loss programmes.
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Affiliation(s)
- G M Cunha
- Liver Imaging Group, Radiology, University of California San Diego, California, USA; MRI Department, Clínica de Diagnóstico por Imagem - CDPI/DASA, Rio de Janeiro, Brazil.
| | - L Lugarino Correa de Mello
- Serviço de Obesidade, Transtornos Alimentares e Metabologia (SOTAM), Instituto Estadual de Endocrinologia (IEDE), Rio de Janeiro, Brazil
| | - K A Hasenstab
- Liver Imaging Group, Radiology, University of California San Diego, California, USA
| | - L Spina
- CliniCoop, Rio de Janeiro, Brazil
| | - I Bussade
- Departamento de Pós-Graduação Em Clínica Médica, Pontifícia Universidade Católica (PUC), Rio de Janeiro, Brazil
| | | | - W Coutinho
- Serviço de Obesidade, Transtornos Alimentares e Metabologia (SOTAM), Instituto Estadual de Endocrinologia (IEDE), Rio de Janeiro, Brazil
| | - G Guzman
- Medical Department Pronokal, Barcelona, Spain
| | - I Sajoux
- Medical Department Pronokal, Barcelona, Spain
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Wang CC, Cheng PN, Kao JH. Systematic review: chronic viral hepatitis and metabolic derangement. Aliment Pharmacol Ther 2020; 51:216-230. [PMID: 31746482 DOI: 10.1111/apt.15575] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 08/08/2019] [Accepted: 10/17/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The liver has a critical role in the metabolism of glucose and lipids. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection leads to a spectrum of liver disease including chronic hepatitis, cirrhosis and hepatocellular carcinoma. Metabolic syndrome (MetS) has a rising incidence owing to an epidemic of type 2 diabetes mellitus (T2DM) and obesity. Non-alcoholic fatty liver disease is a liver manifestation of MetS and has become the most common cause of chronic liver disease worldwide. AIM To summarise the interplay among hepatitis viruses, MetS and its components. METHODS We searched the literature about HBV, HCV infection, MetS, fatty liver and its components from PubMed. RESULTS With respect to the viral replication cycle, lipids are important mediators between viral entry and hepatocyte in HCV infection, but not in HBV infection. Thus, HCV infection is inversely associated with hyperlipidaemia and lipid rebound occurs following sustained viral response induced by interferon-based therapy or direct antiviral agents. In addition, HCV infection is positively associated with insulin resistance, hepatic steatosis, MetS and the risk of T2DM and atherosclerosis. In contrast, HBV infection may protect infected subjects from the development of MetS and hepatic steatosis. Accumulating evidence suggests that HBV infection is inversely associated with lipid metabolism, and exhibits no conclusive association with insulin resistance or the risk of T2DM and arteriosclerosis. CONCLUSIONS In patients with viral hepatitis and concurrent metabolic diseases, a multidisciplinary approach should be given rather than simply antiviral treatment.
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Affiliation(s)
- Chia-Chi Wang
- Department of Gastroenterology and Hepatology, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, Hualien, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, Department of Medical Research and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
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Haghgoo SM, Sharafi H, Alavian SM. Serum cytokines, adipokines and ferritin for non-invasive assessment of liver fibrosis in chronic liver disease: a systematic review. Clin Chem Lab Med 2019; 57:577-610. [PMID: 30231008 DOI: 10.1515/cclm-2018-0357] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Accepted: 07/27/2018] [Indexed: 02/06/2023]
Abstract
Chronic liver disease (CLD) is a major health problem worldwide. Non-alcoholic fatty liver disease (NAFLD), chronic hepatitis C (CHC), chronic hepatitis B (CHB), and alcoholic liver disease (ALD) are the most common etiologies of CLD. Liver biopsy is the gold standard for assessment of liver fibrosis, however, it is an invasive method. This review attempts to evaluate the usefulness of serum adiponectin, serum leptin, serum ferritin, serum transforming growth factor-β1 (TGF-β1), and serum platelet derived growth factor-BB (PDGF-BB) as non-invasive markers in the diagnosis of liver fibrosis/cirrhosis. A systematic search in MEDLINE, Web of Science, Scopus, and local databases was performed to identify articles published in English or Persian as of November 2017. Studies conducted among CLD patients, with biopsy proven fibrosis/cirrhosis, and providing sufficient details of patients' clinicopathological characteristics were included. In the 95 studies included, there were a total of 15,548 CLD patients. More than 83% of studies were carried out in Asia and Europe. The relationship between liver fibrosis/cirrhosis and serum levels of ferritin, adiponectin, leptin, TGF-β1, and PDGF-BB was assessed in 42, 33, 27, nine, and three studies, respectively. Serum levels of the markers, particularly ferritin, could successfully predict liver fibrosis/cirrhosis, however, these data might not be clinically replicated and further studies are needed.
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Affiliation(s)
- Seyyed Mortaza Haghgoo
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.,Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Heidar Sharafi
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.,Middle East Liver Diseases (MELD) Center, Tehran, Iran
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.,Middle East Liver Diseases (MELD) Center, Tehran, Iran
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Elfayoumy KN, Berengy MS, Emran T. Insulin/high-density lipoprotein cholesterol ratio: A newly-discovered predictor of esophageal varices in patients with hepatitis C virus-related cirrhosis in the absence of diabetes mellitus. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:155-162. [PMID: 30541737 DOI: 10.5152/tjg.2018.18237] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND/AIMS Insulin resistance (IR) is closely linked with chronic hepatitis C virus (HCV) and its complications, particularly hepatic fibrosis. The aim of the present study was to investigate some biochemical markers that are potentially related to IR as predictors of esophageal varices (EV) in patients with compensated HCV cirrhosis who do not have diabetes or metabolic syndrome. MATERIALS AND METHODS One hundred subjects without diabetes with compensated HCV-related cirrhosis who did not fulfill the diagnostic criteria of metabolic syndrome were subjected to clinical, laboratory, ultrasonographic, and endoscopic assessments. RESULTS EV were evident in 73 patients with lower platelet counts and high-density lipoprotein cholesterol (HDL-C) levels. On the contrary, the fasting values of both insulin and glucose, the homeostatic model assessment for insulin resistance (HOMA-IR) score, and the bipolar diameter of the spleen of patients with EV were higher than those of other patients who were varices-free. Multivariate analysis confirmed insulin/HDL-C ratio (P=0.01) and HOMA-IR score (P=0.039) as predictors for the presence of varices. The best cut-off values above which the risk of the latter occurrence increased were 0.147 (sensitivity 89%) and 2.24 (sensitivity 72.6%) for both predictors, respectively. CONCLUSION The present study recorded two valid predictors of HCV-related EV: HOMA-IR score and insulin/HDL-C ratio. The latter is more sensitive and is likely more convenient in the case of individuals without diabetes. The validity of two IR-related predictors in the absence of metabolic syndrome confirmed the suggestion that the mechanism of IR-related HCV is different from that of the traditional metabolic syndrome.
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Affiliation(s)
- Khaled Nagy Elfayoumy
- Department of Internal Medicine, Al-Azhar University School of Medicine, New Damietta, Damietta, Egypt
| | - Mahmoud Saad Berengy
- Department of Internal Medicine, Al-Azhar University School of Medicine, New Damietta, Damietta, Egypt
| | - Tarek Emran
- Department Clinical Pathology, Al-Azhar University School of Medicine, New Damietta, Damietta, Egypt
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11
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Diabetes Mellitus and Risk of Hepatic Fibrosis/Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2019; 2019:5308308. [PMID: 31080822 PMCID: PMC6475555 DOI: 10.1155/2019/5308308] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Accepted: 03/27/2019] [Indexed: 02/06/2023]
Abstract
Development of cirrhosis is two- to threefold greater in patients with diabetes mellitus (DM), and in this setting, the prevalence of cirrhosis is surging worldwide. The present review served to examine clinical ties between DM and liver fibrosis and hepatic cirrhosis and explore related biologic mechanisms. Pathways contributing to various etiologies of cirrhosis in conjunction with DM were key investigative targets.
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Andrade VGD, Yamashiro FDS, Oliveira CV, Moreira A, Winckler FC, Silva GF. INSULIN RESISTANCE REDUCTION AFTER SUSTAINED VIROLOGICAL RESPONSE WITH DIRECT ACTING ANTIVIRAL:NOT EVERY POPULATION IMPROVES. ARQUIVOS DE GASTROENTEROLOGIA 2019; 55:274-278. [PMID: 30540091 DOI: 10.1590/s0004-2803.201800000-69] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 08/15/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a serious public health problem, that affects approximately 170 million people worldwide. Chronic HCV infection is associated with hepatic insulin resistance and an increased risk of diabetes HCV-infected patients has been well documented. OBJECTIVE To assess the homeostasis model assessment of insulin resistance (HOMA-IR) index in patients treated with direct acting antiviral (DAAs) medication in the sustained virological response (SVR), categorized by the presence or absence of cirrhosis. METHODS A prospective study was conducted. Data were collected at the beginning of treatment (t-base) and in the twelfth week after the completion of treatment (t-SVR12). The inclusion criteria were presence of: HCV infection (RNA-HCV positive), age ≥18 years, completion of DAAs' therapy, and presence of diabetes with use of oral hypoglycemic agents. All samples were collected during the study period. The exclusion criteria were: presence of HBV/HIV co-infection, hepatocellular carcinoma at baseline, diabetic patients taking insulin and transplanted patients (liver/kidney). Fibrosis was assessed by hepatic elastography or biopsy (METAVIR). Cirrhosis was determined by clinical results or imaging. HOMA-IR was calculated as fasting insulin (μU/mL) × fasting glucose (mmol/L)/22.5) The patients were divided into two groups: the general study population (all patients, including the diabetic patients) and the special population (patients with normal values of HOMA-IR, which is >2.5, and without diabetes). The delta HOMA-IR value was calculated as: HOMA-IR at t-base - HOMA-IR at t-SVR12. For the descriptive statistical analysis, the paired t-test and generalized linear model assuming the log binding function were performed. A P value of < 0.05 was considered significant. RESULTS We included 150 patients, and 75 were cirrhotic. The mean age was 55.3±9.97 and body mass index was 27.4±5.18. Twenty-two (14.67%) were diabetic patients using oral hypoglycemic agents, and 17 (11%) were cirrhotic. In the general study population, the mean glucose and HOMA-IR values increased at t-SVR12, but insulin decreased. Delta HOMA-IR was negative at t-SVR12, but there was no significant difference. Excluding diabetic patients and those with normal HOMA-IR values (<2.5), mean glucose, insulin and HOMA-IR decreased at t-SVR12. Delta HOMA-IR decreased significantly at t-SVR12 (P: 0.02). CONCLUSION In the general population, glucose and HOMA-IR values increased at t-SVR12, but insulin decreased. In the special population, glucose, insulin, HOMA-IR and Delta HOMA-IR decreased at t-SVR12.
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Affiliation(s)
- Vanessa Gutierrez de Andrade
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| | - Fábio da Silva Yamashiro
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| | - Cássio Vieira Oliveira
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| | - Alecsandro Moreira
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| | - Fernanda Cristina Winckler
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| | - Giovanni Faria Silva
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
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Dong TS, Aby ES, Benhammou JN, Kawamoto J, Han SH, May FP, Pisegna JR. Metabolic syndrome does not affect sustained virologic response of direct-acting antivirals while hepatitis C clearance improves hemoglobin A1c. World J Hepatol 2018; 10:612-621. [PMID: 30310539 PMCID: PMC6177571 DOI: 10.4254/wjh.v10.i9.612] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 05/09/2018] [Accepted: 05/23/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To determine whether successful treatment with directacting antivirals (DAA) is associated with improvements in hemoglobin A1c (HbA1c) and if type 2 diabetes mellitus (T2DM) or metabolic syndrome affects sustained virologic response (SVR). METHODS We performed a retrospective analysis of all hepatitis C virus (HCV) patients at the VA Greater Los Angeles Healthcare System treated with varying DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment (SVR12). RESULTS A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2DM. Within that cohort, patients who achieved SVR12 had lower mean HbA1c pre treatment (7.35 vs 8.60, P = 0.02), and lower mean HbA1c post-treatment compared to non-responders (6.55 vs 8.61, P = 0.01). The mean reduction in HbA1c after treatment was greater for those who achieved SVR12 than for non-responders (0.79 vs 0.01, P = 0.03). In adjusted models, patients that achieved SVR12 were more likely to have a HbA1c decrease of ≥ 0.5 than those that did not achieve SVR12 (adjusted OR = 7.24, 95%CI: 1.22-42.94). CONCLUSION In HCV patients with T2DM, successful treatment with DAA was associated with a significant reduction in HbA1c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore, the presence of T2DM or metabolic syndrome does not adversely affect SVR12 rates in patients treated with DAA.
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Affiliation(s)
- Tien S Dong
- the Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States.
| | - Elizabeth S Aby
- the Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
| | - Jihane N Benhammou
- the Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
| | - Jenna Kawamoto
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
| | - Steven-Huy Han
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
- the Pfleger Liver Institute, Department of Surgery, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
| | - Folasade P May
- the Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
- VA Health Services Research and Development Center for the Study of Healthcare Innovation Center for the Study of Healthcare Innovation, Implementation and Policy (CSHIIP), Los Angeles, CA 90073, United States
- Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, United States
| | - Joseph R Pisegna
- the Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
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Yen YH, Lin MT, Kuo FY, Chang KC, Tsai MC, Tseng PL, Wu CK, Lin JT, Hu TH, Lu SN, Wang JH, Hung CH, Chen CH. The association between steatosis and diabetes with hepatocellular carcinoma in non-genotype 3 chronic hepatitis C patients. Liver Int 2018; 38:1064-1073. [PMID: 29164767 DOI: 10.1111/liv.13633] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 11/13/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Diabetes mellitus (DM) has been found to be strongly associated with an increased risk of hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients. Several studies have also found an association between metabolic steatosis and the risk of HCC in CHC patients, whether this latter association has been accounted for by the known relationship between DM and HCC is still unknown. METHODS A cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC and treated with interferon and ribavirin was studied. Cumulative incidence and HCC risk were analysed using the Kaplan-Meier method and Cox proportional hazard analysis. RESULTS Hepatocellular carcinoma developed in 140 subjects over a median follow-up period of 97.3 months, while 699 patients achieved sustained virological response (SVR). According to multivariate analyses, age ≥ 60 years, advanced fibrosis and genotype 1 were identified as independent factors significantly associated with HCC development in SVR patients. Furthermore, using the absence of steatosis and absence of DM as references, the presence of steatosis without DM (HR = 2.09, 95% CI = 1.12-3.9, P = .021), the presence of DM without steatosis (HR = 2.78, 95% CI = 1.3-5.92, P = .008) and the combined presence of steatosis and DM (HR = 3.25, 95% CI = 1.44-7.33, P = .004) were identified as independent factors significantly associated with HCC development in the SVR patients. In contrast, steatosis alone, DM alone and the combined presence of steatosis and DM were not associated with HCC development in non-SVR patients. CONCLUSIONS Steatosis and DM may be associated with HCC development in non-genotype 3 CHC patients with SVR.
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Affiliation(s)
- Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Tsung Lin
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Fang-Ying Kuo
- Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Chin Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Chao Tsai
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Po-Lin Tseng
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Cheng-Kun Wu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jung-Ting Lin
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Wahid B, Rafique S, Saleem K, Ali A, Idrees M. An Increase in Expression of SOCS1 Gene with Increase in Hepatitis C Virus Viral Load. J Interferon Cytokine Res 2018; 38:122-128. [DOI: 10.1089/jir.2017.0129] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Affiliation(s)
- Braira Wahid
- PCR Section, Genome Centre for Molecular Based Diagnostics and Research Centre, Al-Sudais Plaza Abdalian Cooperative Society, Lahore, Pakistan
- Virology Lab, Centre for Applied Molecular Biology (CAMB), Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
| | - Shazia Rafique
- Division of Molecular Virology and Diagnostics Center of Excellence in Molecular Biology (CEMB), Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
| | - Komal Saleem
- PCR Section, Genome Centre for Molecular Based Diagnostics and Research Centre, Al-Sudais Plaza Abdalian Cooperative Society, Lahore, Pakistan
- Virology Lab, Centre for Applied Molecular Biology (CAMB), Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
| | - Amjad Ali
- Virology Lab, Centre for Applied Molecular Biology (CAMB), Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
| | - Muhammad Idrees
- PCR Section, Genome Centre for Molecular Based Diagnostics and Research Centre, Al-Sudais Plaza Abdalian Cooperative Society, Lahore, Pakistan
- Virology Lab, Centre for Applied Molecular Biology (CAMB), Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
- Division of Molecular Virology and Diagnostics Center of Excellence in Molecular Biology (CEMB), Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
- Vice Chancellor Hazara University Mansehra, Pakistan
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Saeed MJ, Olsen MA, Powderly WG, Presti RM. Diabetes Mellitus is Associated With Higher Risk of Developing Decompensated Cirrhosis in Chronic Hepatitis C Patients. J Clin Gastroenterol 2017; 51:70-76. [PMID: 27306942 PMCID: PMC5154898 DOI: 10.1097/mcg.0000000000000566] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
GOALS To investigate the association of diabetes with risk of decompensated cirrhosis in patients with chronic hepatitis C (CHC). BACKGROUND Direct-acting antivirals are highly effective in treating CHC but very expensive. CHC patients at high risk of progression to symptomatic liver disease may benefit most from early treatment. STUDY We conducted a retrospective cohort study using the 2006 to 2013 Truven Health Analytics MarketScan Commercial Claims and Encounters database including inpatient, outpatient, and pharmacy claims from private insurers. CHC and cirrhosis were identified using ICD-9-CM diagnosis codes; baseline diabetes was identified by diagnosis codes or antidiabetic medications. CHC patients were followed to identify decompensated cirrhosis. Multivariable Cox proportional hazards regression was used to model the risk of decompensated cirrhosis by baseline cirrhosis. RESULTS There were 75,805 CHC patients with median 1.9 years follow-up. A total of 10,317 (13.6%) of the CHC population had diabetes. The rates of decompensated cirrhosis per 1000 person-years were: 185.5 for persons with baseline cirrhosis and diabetes, 119.8 for persons with cirrhosis and no diabetes, 35.3 for persons with no cirrhosis and diabetes, and 17.1 for persons with no cirrhosis and no diabetes. Diabetes was associated with increased risk of decompensated cirrhosis in persons with baseline cirrhosis (adjusted hazard ratio=1.4; 95% confidence interval, 1.3-1.6) and in persons without baseline cirrhosis (adjusted hazard ratio=1.9; 95% confidence interval, 1.7-2.1). CONCLUSIONS In a privately insured US population with CHC, the adjusted risk of decompensated cirrhosis was higher in diabetic compared with nondiabetic patients. Diabetes status should be included in prioritization of antiviral treatment.
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Affiliation(s)
- Mohammed J Saeed
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Margaret A Olsen
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - William G Powderly
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Rachel M Presti
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
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Nirei K, Matsumura H, Kumakawa M, Matsumoto N, Nakamura H, Yamagami H, Matsuoka S, Moriyama M. Steatosis influences the clinical profiles and long-term outcomes of interferon-treated chronic hepatitis C and liver cirrhosis patients. Int J Med Sci 2017; 14:45-52. [PMID: 28138308 PMCID: PMC5278658 DOI: 10.7150/ijms.17202] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 11/01/2016] [Indexed: 12/30/2022] Open
Abstract
Objective: This study aimed to assess the relationship between steatosis and long-term outcomes of patients with chronic hepatitis C (CH) and liver cirrhosis (LC). Patients and methods: The study population included 282 subjects with CH or LC who underwent liver biopsy at our institute. All patients achieved a sustained virological response (SVR) to interferon (IFN). Clinical characteristics, including age, gender and body mass index (BMI), were compared. The liver biopsy specimens of all patients were examined and scores were assigned to indicate the severity of each of the following features: inflammatory cell infiltration in the periportal, parenchymal and portal areas; F (fibrosis) stage; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; bile duct damage; hepatic steatosis. Results: Of the 282 patients, 112 (39.7%) were free of steatosis. The other 170 patients (60.3%) had steatosis. The blood biochemical parameters of the patients with hepatic steatosis were significantly poorer than those of patients free of steatosis. Inflammatory cell infiltration and F stage were both significantly more severe in patients with than in those without steatosis. The incidences of hepatocellular carcinoma differed significantly between the two groups. However, the incidences of hepatocellular carcinoma did not differ significantly between the groups with BMI above and below 25. Conclusion: We consider hepatic steatosis to potentially affect the blood biochemical parameters and clinical profiles of Japanese patients with CH due to hepatitis virus type C. Patients with this form of CH showed favorable clinical responses to IFN. Furthermore, fibrosis and steatosis appear to affect the long-term outcomes of these patients. However, BMI alone cannot be used to predict HCC development.
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Affiliation(s)
- Kazushige Nirei
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan 30-1 Oyaguchi Kamicho, Itabashiku, Tokyo 173-8610, Japan
| | - Hiroshi Matsumura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan 30-1 Oyaguchi Kamicho, Itabashiku, Tokyo 173-8610, Japan
| | - Mariko Kumakawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan 30-1 Oyaguchi Kamicho, Itabashiku, Tokyo 173-8610, Japan
| | - Naoki Matsumoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan 30-1 Oyaguchi Kamicho, Itabashiku, Tokyo 173-8610, Japan
| | - Hitomi Nakamura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan 30-1 Oyaguchi Kamicho, Itabashiku, Tokyo 173-8610, Japan
| | - Hiroaki Yamagami
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan 30-1 Oyaguchi Kamicho, Itabashiku, Tokyo 173-8610, Japan
| | - Shunichi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan 30-1 Oyaguchi Kamicho, Itabashiku, Tokyo 173-8610, Japan
| | - Mitsuhiko Moriyama
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan 30-1 Oyaguchi Kamicho, Itabashiku, Tokyo 173-8610, Japan
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Pareek AS, Garger YB, Joshi PM, Romero CM, Seth AK. Secondary Causes of Diabetes Mellitus. PRINCIPLES OF DIABETES MELLITUS 2017:311-326. [DOI: 10.1007/978-3-319-18741-9_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Chang ML, Kuo CJ, Huang HC, Chu YY, Chiu CT. Association between Leptin and Complement in Hepatitis C Patients with Viral Clearance: Homeostasis of Metabolism and Immunity. PLoS One 2016; 11:e0166712. [PMID: 27870883 PMCID: PMC5117713 DOI: 10.1371/journal.pone.0166712] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2016] [Accepted: 11/02/2016] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The association between leptin and complement in hepatitis C virus (HCV) infection remains unknown. METHODS A prospective study was conducted including 474 (250 genotype 1, 224 genotype 2) consecutive chronic hepatitis C (CHC) patients who had completed an anti-HCV therapy course and undergone pre-therapy and 24-week post-therapy assessments of interferon λ3-rs12979860 and HCV RNA/genotypes, anthropometric measurements, metabolic and liver profiles, and complement component 3 (C3), C4, and leptin levels. RESULTS Of the 474 patients, 395 had a sustained virological response (SVR). Pre-therapy leptin levels did not differ between patients with and without an SVR. Univariate and multivariate analyses showed that sex (pre- and post-therapy, p<0.001), body mass index (BMI) (pre- and post-therapy, p<0.001), and C3 levels (pre-therapy, p = 0.027; post-therapy, p = 0.02) were independently associated with leptin levels with or without HCV infection. Pre-therapy BMI, total cholesterol (TC), C4 levels, and the rs12979860 genotype were independently associated with pre-therapy C3 levels in all patients. Post-therapy BMI, alanine aminotransferase, TC, C4 levels, white blood cell counts, and hepatic steatosis were independently associated with the post-therapy C3 levels of SVR patients. Compared with pre-therapy levels, SVR patients showed higher 24-week post-therapy C4 (20.32+/-7.30 vs. 21.55+/-7.07 mg/dL, p<0.001) and TC (171.68+/-32.67 vs. 186.97+/-36.09 mg/dL, p<0.001) levels; however, leptin and C3 levels remained unchanged after therapy in patients with and without an SVR. CONCLUSIONS Leptin and C3 may maintain immune and metabolic homeostasis through association with C4 and TC. Positive alterations in C4 and TC levels reflect viral clearance after therapy in CHC patients.
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Affiliation(s)
- Ming-Ling Chang
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chia-Jung Kuo
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Hsin-Chih Huang
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Yin-Yi Chu
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Cheng-Tang Chiu
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
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Determinant Factors of the Direct Medical Costs Associated with Genotype 1 Hepatitis C Infection in Treatment-Experienced Patients. Drugs R D 2016; 15:335-49. [PMID: 26416653 PMCID: PMC4662942 DOI: 10.1007/s40268-015-0109-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective Limited evidence is available on predictors of medical resource utilization (MRU) and related direct costs, especially in treatment-experienced patients infected with genotype 1 hepatitis C virus (HCV). This study aimed at investigating patient and treatment characteristics that predict MRU and related non-drug costs in treatment-experienced patients with chronic hepatitis C (CHC) treated with simeprevir (SMV) or telapravir (TVR) in combination with pegylated interferon and ribavirin (PegIFN/R). Patients and Methods A total of 709 patients who completed the 72-week ATTAIN trial were included in the study. Cost data were analysed from the UK NHS perspective. Descriptive statistics and regression analyses were used to determine patterns and predictors of total MRU-related costs associated with SMV/PegIFN/R and TVR/PegIFN/R. Results Independent predictors for total MRU-related costs were age, region and the following interaction terms: (1) gender × F3–F4 METAVIR score × baseline viral load (BLVL), (2) body mass index (BMI) × F3–F4 METAVIR score × prior response to PegIFN/R and (3) gender × achievement of SVR at 12 weeks (SVR12) × BLVL. A F3–F4 METAVIR score was a stronger predictor of total MRU-related costs than SVR12. Predictors of adverse events included older age, female gender, low BMI, TVR/PegIFN/R and SVR12. Wilcoxon rank sum test revealed comparable total MRU-related costs between SMV/PegIFN/R and TVR/PegIFN/R. Conclusion To the best of our knowledge, this study is the first to describe the relationship between commonly admitted predictors of MRU-related costs and their joint effect on total MRU-related costs in treatment-experienced patients with CHC. The identified predictors of MRU-related costs suggest that significant treatment costs can be avoided by starting treatment early before the disease progresses. Furthermore, adverse events seem to be the most important factor to take into consideration for the choice of treatment, especially when therapeutic options are associated with similar levels of medical resource utilization and associated costs. Electronic supplementary material The online version of this article (doi:10.1007/s40268-015-0109-5) contains supplementary material, which is available to authorized users.
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Nomair AM, ElDeeb MMK, Maharem DA. Aldose reductase (-106) C/T gene polymorphism and possibility of macrovascular complications in Egyptian type 2 diabetic patients. Indian J Endocrinol Metab 2016; 20:648-655. [PMID: 27730075 PMCID: PMC5040045 DOI: 10.4103/2230-8210.190549] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION Over the past three decades, the number of people with diabetes mellitus (DM) has more than doubled globally, making it one of the most important public health challenges to all nations. Aldose reductase (AR) is a rate-limiting enzyme in the polyol pathway, which has been implicated in the pathogenesis of diabetic microvascular complications; however, the association of the AR gene with diabetic macrovascular complications has rarely been investigated. AIM The study aimed to identify the possible association between C(-106) T polymorphism of the AR gene and diabetic macroangiopathy in a cohort of Egyptian patients with type 2 DM. SETTINGS AND DESIGN This study was conducted on 100 Egyptian subjects, the control group (n = 20) and the patient group (n = 80) with type 2 diabetes which were further subdivided into two subgroups with (n = 48) and without macroangiopathic complications (n = 32) as evidenced by carotid intima-media thickness, electrocardiography (ECG) ischemic changes, cerebrovascular insufficiency, and peripheral vascular insufficiency. SUBJECTS AND METHODS All studied subjects were subjected to detailed history taking, clinical examination, ECG, carotid ultrasonography, routine laboratory investigations, and molecular studies including the detection of AR C(-106) T gene polymorphisms using the polymerase chain reaction (PCR)/restriction fragment length polymorphism technique. RESULTS The genotype distribution and allele frequency of AR C(-106) T showed no statistical significance also the genotypes were not associated with any of the different studied parameters. CONCLUSIONS The results suggest that the C(-106) T polymorphism in the AR gene is not involved in the pathogenesis of macroangiopathy in type 2 diabetes.
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Affiliation(s)
- Azhar Mohamed Nomair
- Department of Chemical Pathology, Medical Research Institute, Alexandria University, Egypt
| | | | - Dalia Aly Maharem
- Department of Internal Medicine, Medical Research Institute, Alexandria University, Egypt
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Adinolfi LE, Rinaldi L, Guerrera B, Restivo L, Marrone A, Giordano M, Zampino R. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations. Int J Mol Sci 2016; 17:ijms17060803. [PMID: 27231906 PMCID: PMC4926337 DOI: 10.3390/ijms17060803] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 05/15/2016] [Accepted: 05/19/2016] [Indexed: 02/06/2023] Open
Abstract
The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV)-associated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases.
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Affiliation(s)
- Luigi Elio Adinolfi
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Luca Rinaldi
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Barbara Guerrera
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Luciano Restivo
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Aldo Marrone
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Mauro Giordano
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Rosa Zampino
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
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Kralj D, Jukić LV, Stojsavljević S, Duvnjak M, Smolić M, Čurčić IB. Hepatitis C Virus, Insulin Resistance, and Steatosis. J Clin Transl Hepatol 2016; 4:66-75. [PMID: 27047774 PMCID: PMC4807145 DOI: 10.14218/jcth.2015.00051] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Revised: 02/15/2016] [Accepted: 02/16/2016] [Indexed: 12/15/2022] Open
Abstract
Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide. Liver steatosis is a common finding in many hepatic and extrahepatic disorders, the most common being metabolic syndrome (MS). Over time, it has been shown that the frequent coexistence of these two conditions is not coincidental, since many epidemiological, clinical, and experimental studies have indicated HCV to be strongly associated with liver steatosis and numerous metabolic derangements. Here, we present an overview of publications that provide clinical evidence of the metabolic effects of HCV and summarize the available data on the pathogenetic mechanisms of this association. It has been shown that HCV infection can induce insulin resistance (IR) in the liver and peripheral tissues through multiple mechanisms. Substantial research has suggested that HCV interferes with insulin signaling both directly and indirectly, inducing the production of several proinflammatory cytokines. HCV replication, assembly, and release from hepatocytes require close interactions with lipid droplets and host lipoproteins. This modulation of lipid metabolism in host cells can induce hepatic steatosis, which is more pronounced in patients with HCV genotype 3. The risk of steatosis depends on several viral factors (including genotype, viral load, and gene mutations) and host features (visceral obesity, type 2 diabetes mellitus, genetic predisposition, medication use, and alcohol consumption). HCV-related IR and steatosis have been shown to have a remarkable clinical impact on the prognosis of HCV infection and quality of life, due to their association with resistance to antiviral therapy, progression of hepatic fibrosis, and development of hepatocellular carcinoma. Finally, HCV-induced IR, oxidative stress, and changes in lipid and iron metabolism lead to glucose intolerance, arterial hypertension, hyperuricemia, and atherosclerosis, resulting in increased cardiovascular mortality.
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Affiliation(s)
- Dominik Kralj
- Department of Gastroenterology and Hepatology, Sisters of Charity University Hospital Center, Zagreb, Croatia
| | - Lucija Virović Jukić
- Department of Gastroenterology and Hepatology, Sisters of Charity University Hospital Center, Zagreb, Croatia
| | - Sanja Stojsavljević
- Department of Gastroenterology and Hepatology, Sisters of Charity University Hospital Center, Zagreb, Croatia
| | - Marko Duvnjak
- Department of Gastroenterology and Hepatology, Sisters of Charity University Hospital Center, Zagreb, Croatia
| | - Martina Smolić
- Department of Pharmacology, Faculty of Medicine, University of Osijek, Osijek, Croatia
| | - Ines Bilić Čurčić
- Department of Pharmacology, Faculty of Medicine, University of Osijek, Department of Endocrinology and metabolism disorders, University Hospital Center, Osijek, Osijek, Croatia
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24
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Vanni E, Bugianesi E, Saracco G. Treatment of type 2 diabetes mellitus by viral eradication in chronic hepatitis C: Myth or reality? Dig Liver Dis 2016; 48:105-11. [PMID: 26614641 DOI: 10.1016/j.dld.2015.10.016] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 10/05/2015] [Accepted: 10/16/2015] [Indexed: 12/15/2022]
Abstract
Chronic hepatitis C is a systemic disease inducing metabolic alterations leading to extrahepatic consequences. In particular, hepatitis C virus (HCV) infection seems to increase the risk of incident type 2 diabetes mellitus in predisposed individuals, independently of liver disease stage. The mechanisms through which hepatitis C induces T2DM involve direct viral effects, insulin resistance, pro-inflammatory cytokines and other immune-mediated processes. Many studies have reported the clinical consequences of type 2 diabetes mellitus on hepatitis C outcome, but very few studies have addressed the issue of microangiopathic complications among patients with hepatitis C only, who develop type 2 diabetes mellitus. Moreover, clinical trials in HCV-positive patients have reported improvement in glucose metabolism after antiviral treatment; recent studies have suggested that this metabolic amelioration might have a clinical impact on type 2 diabetes mellitus-related complications. These observations raise the question as to whether the HCV eradication may also have an impact on the future morbidity and mortality due to type 2 diabetes mellitus. The scope of this review is to summarise the current evidence linking successful antiviral treatment and the prevention of type 2 diabetes mellitus and its complications in hepatitis C-infected patients.
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Affiliation(s)
- Ester Vanni
- Gastro-hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Elisabetta Bugianesi
- Gastro-hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Giorgio Saracco
- Gastroenterology Unit, Oncology Department, University of Turin, Italy.
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25
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Knobler H, Malnick S. Hepatitis C and insulin action: An intimate relationship. World J Hepatol 2016; 8:131-138. [PMID: 26807209 PMCID: PMC4716529 DOI: 10.4254/wjh.v8.i2.131] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2015] [Revised: 12/10/2015] [Accepted: 12/29/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection has been shown to be linked to a higher prevalence of type 2 diabetes compared with the general population or with patients with chronic hepatitis B infection and diabetes is the most common extra-hepatic manifestation of HCV. The HCV-diabetes association is due to insulin resistance (IR) that occurs early in the course of the disease even in patients without or with minimal fibrosis. The mechanisms for HCV-induced IR are only partly understood and include a direct inhibitory effect of HCV on insulin signaling pathway. IR in chronic HCV results in an increased progression rate of hepatic fibrosis, cirrhosis and hepatocellular carcinoma. Some but not all studies found that IR reduces the response rate to interferon/ribavirin therapy. Whether IR affects the response to the new direct-acting antiviral treatments is still unknown.
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Affiliation(s)
- Hilla Knobler
- Hilla Knobler, Diabetes and Metabolic Disease Unit, Kaplan Medical Center, Rehovot 76100, Israel
| | - Stephen Malnick
- Hilla Knobler, Diabetes and Metabolic Disease Unit, Kaplan Medical Center, Rehovot 76100, Israel
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26
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Abstract
Hepatitis C infection is a common cause of cirrhosis and indication for liver transplantation in the United States. The incidence of chronic hepatitis C has been declining, but rates of cirrhosis and hepatocellular carcinoma are projected to increase. The outcome of chronic hepatitis C is variable. It is estimated that 20% to 25% will develop cirrhosis over a 25-year to 30-year period. The rate of disease progression is influenced by many host, viral, and environmental factors. Few can be modified.
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Chettouh H, Lequoy M, Fartoux L, Vigouroux C, Desbois-Mouthon C. Hyperinsulinaemia and insulin signalling in the pathogenesis and the clinical course of hepatocellular carcinoma. Liver Int 2015; 35:2203-17. [PMID: 26123841 DOI: 10.1111/liv.12903] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 06/09/2015] [Indexed: 12/11/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and is one of the leading causes of cancer-related death. The risk factors for HCC include cirrhosis, chronic viral hepatitis, heavy alcohol intake and metabolic diseases such as obesity, type 2 diabetes and metabolic syndrome. Insulin resistance is a common denominator of all of these conditions and is tethered to hyperinsulinaemia. Here, we give an overview of the recent advances linking hyperinsulinaemia to HCC development and progression. In particular, we summarise the underlying causes of hyperinsulinaemia in the setting of chronic liver diseases. We present epidemiological evidence linking metabolic diseases to HCC risk and HCC-related mortality, as well as the pathogenic cellular and molecular mechanisms explaining this relation. A better understanding of the mechanisms by which insulin participates in HCC biology might ultimately provide novel opportunities for prevention and treatment.
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Affiliation(s)
- Hamza Chettouh
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France
| | - Marie Lequoy
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,Service d'Hépatologie, AP-HP, Hôpital Saint-Antoine, Paris, France
| | - Laetitia Fartoux
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,Service d'Hépatologie, AP-HP, Hôpital Saint-Antoine, Paris, France
| | - Corinne Vigouroux
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,Laboratoire Commun de Biologie et Génétique Moléculaires AP-HP, Hôpital Saint-Antoine, Paris, France.,ICAN, Institute of Cardiometabolism and Nutrition, Paris, France
| | - Christèle Desbois-Mouthon
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.,INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France
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28
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Giustina RD, Marconcini ML, Bansho ETO, Tonon D, Pasinato APBF, Dantas-Corrêa EB, Schiavon LL, Narciso-Schiavon JL. Factors associated with steatosis in liver biopsies of individuals with chronic hepatitis C infection in southern Brazil. Arab J Gastroenterol 2015; 16:59-62. [PMID: 26169501 DOI: 10.1016/j.ajg.2015.06.002] [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: 03/09/2015] [Revised: 06/04/2015] [Accepted: 06/20/2015] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND STUDY AIMS Infection by the hepatitis C virus (HCV) is associated with various metabolic disorders that are collectively referred to as dysmetabolic syndrome associated with HCV. Hepatic steatosis is a common finding in chronic HCV infection and has been reported in 30-70% of patients. Here, we determine the prevalence of steatosis in patients with HCV, identify the characteristics associated with the presence of steatosis in liver biopsies and assess the association between steatosis and the severity of liver disease. PATIENTS AND METHODS This analytic cross-sectional study evaluated HCV carriers (adults) at the Gastroenterology and Hepatology Outpatient Clinic of a public university hospital between July 2013 and June 2014 using retrospective data collection. The patients were divided into two groups according to the presence or absence of steatosis in their liver biopsies. The groups were compared for the presence of risk factors for steatosis and clinical, laboratory, virological and histological characteristics. RESULTS One hundred and four patients aged 49.5±9.3 years were included in the study; 56.0% of the patients were men. Steatosis was observed in 65.4% of the liver biopsies. When comparing individuals with and without steatosis, patients with steatosis exhibited a higher proportion of non-1 genotype (43.9 vs. 20.7%; p=0.034), higher median triglyceride levels (101.0 vs. 75.0; p=0.034), ferritin levels (333.0 vs. 193.5; p=0.025) and gamma glutamyl transferase levels (2.92 xULN vs. 1.87; p=0.030). Multivariate analysis demonstrated that triglyceride levels were independently associated with the presence of steatosis (OR=1.016; 95% CI 1.002-1.031; p=0.026). CONCLUSIONS Hepatic steatosis was observed in 65.4% of individuals with HCV. We observed that elevated triglyceride levels were associated independently with the presence of hepatic steatosis; we did not demonstrate an association between hepatic steatosis and histological severity.
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Affiliation(s)
- Renata D Giustina
- Núcleo de Estudos em Gastroenterologia e Hepatologia, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil
| | - Maíra L Marconcini
- Núcleo de Estudos em Gastroenterologia e Hepatologia, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil
| | - Emilia T O Bansho
- Núcleo de Estudos em Gastroenterologia e Hepatologia, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil
| | - Débora Tonon
- Núcleo de Estudos em Gastroenterologia e Hepatologia, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil
| | - Ana P B F Pasinato
- Serviço de Anatomia Patológica (SAP) - University Hospital Polydoro Ernani de São Thiago, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil
| | - Esther B Dantas-Corrêa
- Núcleo de Estudos em Gastroenterologia e Hepatologia, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil
| | - Leonardo L Schiavon
- Núcleo de Estudos em Gastroenterologia e Hepatologia, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil
| | - Janaína L Narciso-Schiavon
- Núcleo de Estudos em Gastroenterologia e Hepatologia, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil.
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29
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Coppo C, Bonfanti D, Bo S, Giordanino C, Gallo M, Cococcia S, Ciccone G, Smedile A, Ciancio A, Bugianesi E, Fagoonee S, Pellicano R, Rizzetto M, Saracco GM. Risk of microangiopathy in type 2 diabetes mellitus patients with or without chronic hepatitis C: Results of a retrospective long-term controlled cohort study. Dig Liver Dis 2015; 47:405-410. [PMID: 25733341 DOI: 10.1016/j.dld.2015.01.157] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 01/26/2015] [Accepted: 01/29/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND Patients with chronic hepatitis C have an increased risk of diabetes mellitus but the type and risk of developing diabetes-related complications have not yet been evaluated. METHODS In order to compare the incidence of diabetic microangiopathy in patients with new onset diabetes without microangiopathy we recruited 54 hepatitis C virus (HCV)-positive and 119 HCV-negative patients from January 2005 to December 2006. All patients were followed-up every 6 months for liver and diabetic complications and incidence of cardiovascular diseases up to December 2012 when data were retrospectively analyzed. RESULTS The two cohorts were comparable at enrolment except for mean body mass index, obesity rate and family history of diabetes (p=0.007). After 7.2 years of follow-up, 13 HCV-positive (24.1%) and 37 HCV-negative patients (31%) showed at least one microangiopathic complication (p=0.34); 5 HCV-positive (9.3%) and 13 HCV-negative patients (10.8%) reported cardiovascular diseases (p=0.2); 14 HCV-positive (24.5%) compared to 0 HCV-negative patients developed liver-related complications (p=0.0003). One HCV-positive patient died due to liver cancer, 1 HCV-negative patient died from myocardial infarction (p=0.3). Increasing age (HR=1.04, 95% CI: 1.00-1.07, p=0.04) and smoking (HR=2.94, 95% CI: 1.06-8.17, p=0.04) were positively associated to diabetic complications. CONCLUSIONS Incidence of microangiopathy is not significantly different in diabetics with or without chronic hepatitis C.
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Affiliation(s)
- Claudia Coppo
- Gastroenterology Unit, Department of Oncology, University of Turin, Turin, Italy
| | - Daria Bonfanti
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Simona Bo
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Chiara Giordanino
- Gastroenterology Unit, Department of Oncology, University of Turin, Turin, Italy
| | - Monica Gallo
- Gastroenterology Unit, Department of Oncology, University of Turin, Turin, Italy
| | - Sara Cococcia
- Gastroenterology Unit, Department of Oncology, University of Turin, Turin, Italy
| | - Giovannino Ciccone
- Unit of Cancer Epidemiology, University of Turin, Molinette Hospital and CPO Piemonte, Turin, Italy
| | - Antonina Smedile
- Gastro-Hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Alessia Ciancio
- Gastro-Hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Elisabetta Bugianesi
- Gastro-Hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Sharmila Fagoonee
- Institute for Biostructures and Bioimages (CNR), Molecular Biotechnology Center, University of Turin, Italy
| | - Rinaldo Pellicano
- Gastro-Hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Mario Rizzetto
- Gastro-Hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
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Akpo EIH, Cerri K, Kleintjens J. Predicting the impact of adverse events and treatment duration on medical resource utilization-related costs in hepatitis C genotype 1 treatment-naïve patients receiving antiviral therapy. PHARMACOECONOMICS 2015; 33:409-422. [PMID: 25577042 PMCID: PMC4381112 DOI: 10.1007/s40273-014-0249-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
OBJECTIVES Studies on medical resource utilization (MRU) and related costs are important for evaluating the potential patient management and cost-effectiveness implications of antiviral treatments for hepatitis C virus (HCV) infection. The objectives of this study were (i) to compare the MRU and related costs for two treatment approaches; (ii) to identify the main drivers of resource use and costs; and (iii) to assess the effects of various treatment regimen attributes on MRU-related costs in a UK clinical setting. METHODS The analysis used data collected alongside the simeprevir (SMV) phase III trials for treatment-naïve genotype 1 HCV-infected patients; these data covered outpatient consultations with specialists, emergency room visits and hospital admissions. Logistic regressions were constructed to estimate the predictors of resource utilization, and a two-part multivariable analysis model was used to determine the total costs of treatment in the UK. RESULTS Data on 731 patients receiving SMV plus pegylated interferon and ribavirin (SMV/PegIFN/R) or PegIFN/R were included in the analysis. While MRU was similar between the SMV and PegIFN/R groups, MRU-related costs were significantly lower in the SMV group than in the PegIFN/R group (P < 0.05). High body mass index (P < 0.05), severe fibrosis (P < 0.05), shortened treatment duration to 24 weeks (P < 0.05), and anaemia and rash during treatment (P < 0.001) were identified as predictors of hospitalization and outpatient visits and as drivers of total costs. Univariate sensitivity analyses suggested that shortened treatment duration and lower occurrence of rash lead to large cost savings. CONCLUSION This study identified both baseline and on-treatment antiviral therapy characteristics as drivers of MRU-related costs for HCV patients following antiviral therapy. The shortened treatment duration and reduction in rash due to treatment with SMV triple therapy lead to substantial non-drug cost savings, compared with PegIFN/R treatment. This suggests that there are potential patient management and cost-effectiveness implications associated with the choice of specific antiviral treatments.
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31
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Kalafateli M, Triantos C, Tsochatzis E, Michalaki M, Koutroumpakis E, Thomopoulos K, Kyriazopoulou V, Jelastopulu E, Burroughs A, Lambropoulou-Karatza C, Nikolopoulou V. Adipokines levels are associated with the severity of liver disease in patients with alcoholic cirrhosis. World J Gastroenterol 2015; 21:3020-3029. [PMID: 25780301 PMCID: PMC4356923 DOI: 10.3748/wjg.v21.i10.3020] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2014] [Revised: 10/31/2014] [Accepted: 12/14/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the adipokine levels of leptin, adiponectin, resistin, visfatin, retinol-binding protein 4 (RBP4), apelin in alcoholic liver cirrhosis (ALC). METHODS Forty non-diabetic ALC patients [median age: 59 years, males: 35 (87.5%), Child-Pugh (CP) score: median 7 (5-12), CP A/B/C: 18/10/12, Model for End-stage Liver Disease (MELD): median 10 (6-25), follow-up: median 32.5 mo (10-43)] were prospectively included. The serum adipokine levels were estimated in duplicate by ELISA. Somatometric characteristics were assessed with tetrapolar bioelectrical impedance analysis. Pearson's rank correlation coefficient was used to assess possible associations with adipokine levels. Univariate and multivariate Cox regression analysis was used to determine independent predictors for overall survival. RESULTS Body mass index: median 25.9 (range: 20.1-39.3), fat: 23.4% (7.6-42.1), fat mass: 17.8 (5.49-45.4), free fat mass: 56.1 (39.6-74.4), total body water (TBW): 40.6 (29.8-58.8). Leptin and visfatin levels were positively associated with fat mass (P < 0.001/P = 0.027, respectively) and RBP4 with TBW (P = 0.025). Median adiponectin levels were significantly higher in CPC compared to CPA (CPA: 7.99 ± 14.07, CPB: 7.66 ± 3.48, CPC: 25.73 ± 26.8, P = 0.04), whereas median RBP4 and apelin levels decreased across the spectrum of disease severity (P = 0.006/P = 0.034, respectively). Following adjustment for fat mass, visfatin and adiponectin levels were significantly increased from CPA to CPC (both P < 0.001), whereas an inverse correlation was observed for both RBP4 and apelin (both P < 0.001). In the multivariate Cox regression analysis, only MELD had an independent association with overall survival (HR = 1.53, 95%CI: 1.05-2.32; P = 0.029). CONCLUSION Adipokines are associated with deteriorating liver function in a complex manner in patients with alcoholic liver cirrhosis.
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32
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Jain MK, Adams-Huet B, Terekhova D, Kushner LE, Bedimo R, Li X, Holodniy M. Acute and chronic immune biomarker changes during interferon/ribavirin treatment in HIV/HCV co-infected patients. J Viral Hepat 2015; 22:25-36. [PMID: 24506344 PMCID: PMC4127161 DOI: 10.1111/jvh.12226] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Accepted: 12/04/2013] [Indexed: 12/14/2022]
Abstract
Chronic viral infections lead to persistent immune activation, which is alleviated by eradicating or suppressing the infection. To understand the effects of interferon treatment on immune system activation by chronic infections, we evaluated kinetic patterns of a broad spectrum of serum biomarkers during HCV treatment in HIV/HCV co-infected patients. HCV viral load and 50 biomarkers were analysed at baseline and 27 time points during pegylated interferon-alpha and ribavirin (IFN/RBV) treatment of 12 HIV/HCV co-infected patients. We evaluated biomarker changes from baseline for each time point and biomarker correlations with clinical parameters, treatment response and liver histopathology. IL-1α, IL-12p40, IL-1RA, IP-10, MIG, MIP-1α/1β, HGF, sCD40L, TRAIL and leptin increased in the first day. IL-12p70, IL-17A, IL-10, GROα, IL-8, MCP-3, IL-4 and M-CSF peaked later during week 1. IL-1α, HGF, IP-10, MIP-1α, TRAIL, sCD40L, IL-10, IL-12p70, MCP-3, FGFb, ENA-78, TGF-β, IL-2, IFN-γ, IL-6, IL-15, IL-7 and PDGF-BB decreased below baseline over the course of treatment. Higher BMI, baseline HCV viral load and leptin levels were associated with lack of sustained virologic response. ENA-78 was associated with sustained viral response. Positive correlations were found between liver inflammation and baseline CD4 count, sVCAM and HGF; fibrosis stage and HGF; liver steatosis, BMI and leptin. Our findings suggest IFN/RBV treatment initially increases levels of several biomarkers, but eventually leads to a decline in many immune markers. These findings shed light on the relationship between IFN treatment and immune activation by chronic viral infections, such as HCV.
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Affiliation(s)
- Mamta K. Jain
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - Beverley Adams-Huet
- Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX
| | - Darya Terekhova
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - Lauren E. Kushner
- AIDS Research Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA
| | - Roger Bedimo
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
,Department of Internal Medicine, North Texas VA Medical Center, Dallas, TX
| | - Xilong Li
- Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX
| | - Mark Holodniy
- AIDS Research Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA
,Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States
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Lonardo A, Adinolfi LE, Restivo L, Ballestri S, Romagnoli D, Baldelli E, Nascimbeni F, Loria P. Pathogenesis and significance of hepatitis C virus steatosis: an update on survival strategy of a successful pathogen. World J Gastroenterol 2014; 20:7089-7103. [PMID: 24966582 PMCID: PMC4064057 DOI: 10.3748/wjg.v20.i23.7089] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 01/17/2014] [Accepted: 04/01/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a successful pathogen on the grounds that it exploits its host's metabolism to build up viral particles; moreover it favours its own survival by inducing chronic disease and the development of specific anatomic changes in the infected organ. Steatosis, therefore, is associated with HCV infection by necessity rather than by chance alone. Approximately 6% of HCV patients have steatohepatitis. Interestingly, HCV steatosis occurs in the setting of multiple metabolic abnormalities (hyperuricemia, reversible hypocholesterolemia, insulin resistance, arterial hypertension and expansion of visceral adipose tissue) collectively referred to as "hepatitis C-associated dysmetabolic syndrome" (HCADS). General, nonalcoholic fatty liver disease (NAFLD)-like, mechanisms of steatogenesis (including increased availability of lipogenic substrates and de novo lipogenesis; decreased oxidation of fatty substrates and export of fatty substrates) are shared by all HCV genotypes. However, genotype 3 seemingly amplifies such steatogenic molecular mechanisms reported to occur in NAFLD via more profound changes in microsomal triglyceride transfer protein; peroxisome proliferator-activated receptor alpha; sterol regulatory element-binding proteins and phosphatase and tensin homologue. HCV steatosis has a remarkable clinical impact in as much as it is an acknowledged risk factor for accelerated fibrogenesis; for impaired treatment response to interferon and ribavirin; and development of hepatocellular carcinoma. Recent data, moreover, suggest that HCV-steatosis contributes to premature atherogenesis via both direct and indirect mechanisms. In conclusion, HCV steatosis fulfills all expected requirements necessary to perpetuate the HCV life cycle. A better understanding of the physiology of HCADS will likely result in a more successful handling of disease with improved antiviral success rates.
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Mastroianni CM, Lichtner M, Mascia C, Zuccalà P, Vullo V. Molecular mechanisms of liver fibrosis in HIV/HCV coinfection. Int J Mol Sci 2014; 15:9184-208. [PMID: 24865485 PMCID: PMC4100089 DOI: 10.3390/ijms15069184] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2014] [Revised: 05/15/2014] [Accepted: 05/15/2014] [Indexed: 12/14/2022] Open
Abstract
Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV). Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.
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Affiliation(s)
- Claudio M Mastroianni
- Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
| | - Miriam Lichtner
- Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
| | - Claudia Mascia
- Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
| | - Paola Zuccalà
- Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
| | - Vincenzo Vullo
- Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
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Imran M, Manzoor S, Ashraf J, Khalid M, Tariq M, Khaliq HM, Azam S. Role of viral and host factors in interferon based therapy of hepatitis C virus infection. Virol J 2013; 10:299. [PMID: 24079723 PMCID: PMC3849893 DOI: 10.1186/1743-422x-10-299] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2013] [Accepted: 09/24/2013] [Indexed: 02/07/2023] Open
Abstract
The current standard of care (SOC) for hepatitis C virus (HCV) infection is the combination of pegylated interferon (PEG-IFN), Ribavirin and protease inhibitor for HCV genotype 1. Nevertheless, this treatment is successful only in 70-80% of the patients. In addition, the treatment is not economical and is of immense physical burden for the subject. It has been established now, that virus-host interactions play a significant role in determining treatment outcomes. Therefore identifying biological markers that may predict the treatment response and hence treatment outcome would be useful. Both IFN and Ribavirin mainly act by modulating the immune system of the patient. Therefore, the treatment response is influenced by genetic variations of the human as well as the HCV genome. The goal of this review article is to summarize the impact of recent scientific advances in this area regarding the understanding of human and HCV genetic variations and their effect on treatment outcomes. Google scholar and PubMed have been used for literature research. Among the host factors, the most prominent associations are polymorphisms within the region of the interleukin 28B (IL28B) gene, but variations in other cytokine genes have also been linked with the treatment outcome. Among the viral factors, HCV genotypes are noteworthy. Moreover, for sustained virological responses (SVR), variations in core, p7, non-structural 2 (NS2), NS3 and NS5A genes are also important. However, all considered single nucleotide polymorphisms (SNPs) of IL28B and viral genotypes are the most important predictors for interferon based therapy of HCV infection.
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Affiliation(s)
- Muhammad Imran
- Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology (NUST), 44000 Islamabad, Pakistan.
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Komase K, Maekawa S, Miura M, Sueki R, Kadokura M, Shindo H, Shindo K, Amemiya F, Nakayama Y, Inoue T, Sakamoto M, Yamashita A, Moriishi K, Enomoto N. Serum RANTES level influences the response to pegylated interferon and ribavirin therapy in chronic hepatitis C. Hepatol Res 2013; 43:865-75. [PMID: 23279319 DOI: 10.1111/hepr.12032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2012] [Revised: 11/18/2012] [Accepted: 11/26/2012] [Indexed: 02/08/2023]
Abstract
AIM Prediction of treatment responses to pegylated interferon (PEG IFN) plus ribavirin (RBV) therapy is uncertain for genotype 1b chronic hepatitis C. METHODS In this study, 96 patients were investigated for the correlation between 36 pretreatment serum chemokine/cytokine levels and PEG IFN/RBV treatment efficacy by a sandwich enzyme-linked immunoassay (ELISA) and a bead array. RESULTS First, chemokines/cytokines were measured semiquantitatively by sandwich ELISA in 31 randomly-selected patients and the serum regulated on activation normal T-cell expressed and secreted (RANTES) level was found to be significantly higher in the sustained virological response (SVR) group than the non-SVR group (P = 0.048). Precise RANTES measurement in all 96 patients using a bead array confirmed this correlation (P = 0.002). However, the genetic RANTES haplotype was not significantly related to the serum level. The serum RANTES level was extracted by multivariate analysis (odds ratio = 4.09, 95% confidence interval = 1.02-16.5, P = 0.048) as an independent variable contributing to SVR. CONCLUSION The serum RANTES level is an important determinant influencing the virological response to PEG IFN/RBV therapy in chronic hepatitis C.
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Affiliation(s)
- Kazuki Komase
- First Department of Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
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Ezzat WM, Elhosary YA, Abdulla NA, Raslan HM, Saleh OM, Ibrahim MH, Rasheed MA, El-Hariri H. Insulin resistance and early virological response in chronic HCV infection. J Genet Eng Biotechnol 2013. [DOI: 10.1016/j.jgeb.2012.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Shiraki M, Nishiguchi S, Saito M, Fukuzawa Y, Mizuta T, Kaibori M, Hanai T, Nishimura K, Shimizu M, Tsurumi H, Moriwaki H. Nutritional status and quality of life in current patients with liver cirrhosis as assessed in 2007-2011. Hepatol Res 2013; 43:106-12. [PMID: 23409849 DOI: 10.1111/hepr.12004] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2012] [Revised: 10/07/2012] [Accepted: 10/15/2012] [Indexed: 02/08/2023]
Abstract
AIM Current guidelines recommended adequate nutritional support for patients with liver cirrhosis to improve clinical outcome and quality of life (QOL). However, these evidences were obtained more than 10 years ago when malnutrition prevailed. In recent years, the impact of obesity on liver damage and carcinogenesis has grown. We attempted to elucidate the nutritional state and QOL in present cirrhotics. METHODS A research group supported by the Ministry of Health, Labor and Welfare of Japan recruited 294 cirrhotics between 2007 and 2011. Subjects comprised 171 males and 123 females, 158 of whom had hepatocellular carcinoma (HCC) and Child-Pugh grades A : B : C were 154:91:49. Anthropometry, blood biochemistry and indirect calorimetry were conducted, and QOL was measured using Short Form-8. RESULTS The mean body mass index (BMI) of all patients was 23.1 ± 3.4 kg/m(2) , and 31% showed obesity (BMI ≥ 25.0). In subjects without ascites, edema or HCC, mean BMI was 23.6 ± 3.6, and 34% had obesity. Protein malnutrition defined as serum albumin of less than 3.5 g/dL and energy malnutrition as respiratory quotient of less than 0.85 appeared in 61% and 43%, respectively, and protein-energy malnutrition (PEM) in 27% of all subjects. Among subjects without HCC, each proportion was 67%, 48% and 30%, respectively. QOL was significantly lower on all subscales than Japanese national standard values, but was similar regardless the presence or absence of HCC. CONCLUSION While PEM is still present in liver cirrhosis, an equal proportion has obesity in recent patients. Thus, in addition to guidelines for PEM, establishment of nutrition and exercise guidelines seems essential for obese patients with liver cirrhosis.
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Affiliation(s)
- Makoto Shiraki
- The First Department of Internal Medicine, Gifu University School of Medicine, Gifu
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Gheit SA, Keddeas MW, Safwat E. Rapid virological response as a predictor of a sustained virological response in Egyptian patients with chronic hepatitis C genotype 4. EGYPTIAN LIVER JOURNAL 2013. [DOI: 10.1097/01.elx.0000424248.63976.02] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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40
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Giordanino C, Ceretto S, Bo S, Smedile A, Ciancio A, Bugianesi E, Pellicano R, Fagoonee S, Versino E, Costa G, Arese D, Sacco M, Rizzetto M, Saracco G. Type 2 diabetes mellitus and chronic hepatitis C: which is worse? Results of a long-term retrospective cohort study. Dig Liver Dis 2012; 44:406-412. [PMID: 22245505 DOI: 10.1016/j.dld.2011.12.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2011] [Revised: 11/30/2011] [Accepted: 12/05/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUND The long-term outcome in patients with chronic hepatitis C and type 2 diabetes mellitus treated with interferon and ribavirin is unclear. We compared incidence of liver-related events and mortality rates between hepatitis C virus-positive patients with or without diabetes mellitus, and the incidence of diabetes-related events between diabetic patients with and without hepatitis C. METHODS Retrospective study of 309 patients with chronic hepatitis C. Incidence of liver-related events, diabetes-related events and mortality rates were assessed over a mean follow-up of 11.02±4.9 years. RESULTS 50 (16%) chronic hepatitis C patients had diabetes mellitus. Diabetics showed a higher number of diabetes- and liver-related events than non-diabetics (10% vs 1.5%, p=0.006; 18% vs 5.7%, p=0.007, respectively) with a mortality of 14% vs 1.5% (p=0.0003). Baseline cirrhosis (p=0.002) and non-sustained virological response (p=0.01) were independent risk factors for liver events; diabetes mellitus (p=0.01) and hypertension (p=0.0017) were independent factors for diabetes-related events. CONCLUSIONS In patients with chronic hepatitis C, comorbidity with diabetes mellitus was associated with a higher mortality rate and incidence of liver/diabetes-related events. Independent risk factors for liver-related events were the non-response to antiviral therapy and cirrhosis at baseline.
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Affiliation(s)
- Chiara Giordanino
- Division of Gastroenterology, University of Turin, San Luigi Medical School, Orbassano, Italy.
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Abstract
This review will focus on the impact of steatosis and insulin resistance on the response to antiviral therapy for chronic hepatitis C. Hepatitis C virus (HCV) infection is known to have direct and/or indirect effects on lipid and glucose metabolism, leading to, among other disturbances, steatosis and insulin resistance, respectively. Some of these disturbances have a marked HCV genotype distribution. For example, on average, patients with HCV genotype 3 have the highest prevalence and severity of viral fatty liver. On the other hand, the current global spread of the metabolic syndrome represents a formidable cofactor of morbidity in HCV-related chronic liver disease. Thus, the pathogenesis of steatosis and insulin resistance in patients with chronic hepatitis C may often be dual, i.e. viral and metabolic. This distinction is relevant because the effect (if any) of steatosis or insulin resistance on the response to antiviral agents seems to depend on their pathogenesis. Accumulating data suggest that viral fatty liver may not impact on response to therapy, while metabolic steatosis does. Similarly, viral insulin resistance may not reduce the rate of response to therapy to the same extent that metabolic insulin resistance does. Some implications for patient management are discussed.
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Affiliation(s)
- F Negro
- Divisions of Gastroenterology and Hepatology and Clinical Pathology, University Hospitals, Geneva, Switzerland.
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Mizuta T. Can exercise be a new approach for chronic hepatitis C? Hepatol Res 2011; 41:925-7. [PMID: 21951871 DOI: 10.1111/j.1872-034x.2011.00885.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Toshihiko Mizuta
- Department of Internal Medicine, Saga Medical School, Saga, Japan
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Kaddai V, Negro F. Current understanding of insulin resistance in hepatitis C. Expert Rev Gastroenterol Hepatol 2011; 5:503-16. [PMID: 21780897 DOI: 10.1586/egh.11.43] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Important breakthroughs have been made in recent years into understanding the close interaction between hepatitis C virus (HCV) infection and glucose homeostasis. Both cross-sectional and longitudinal studies have demonstrated that infection with HCV is associated with an increased risk of developing insulin resistance and Type 2 diabetes. A direct effect of HCV on hepatocyte insulin signaling has been shown in experimental models. Some preliminary observations seem to suggest that indirect mechanisms involving extrahepatic organs might also play a role. The interaction between HCV and glucose metabolism has significant clinical consequences. Insulin resistance and Type 2 diabetes not only accelerate the histological and clinical progression of chronic hepatitis C, but also reduce the virological response to IFN-α-based therapy. Thus, understanding the mechanisms underlying HCV-associated glucose metabolism derangements is of paramount interest in order to improve the clinical management of chronic hepatitis C. This article will focus on the studies that consistently argue in favor of an interrelation between HCV and insulin resistance and will highlight the latest discoveries in this field.
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Affiliation(s)
- Vincent Kaddai
- Department of Pathology and Immunology, Centre Médical Universitaire, Rue Michel-Servet 1, Geneva, Switzerland
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Nobili V, Carter-Kent C, Feldstein AE. The role of lifestyle changes in the management of chronic liver disease. BMC Med 2011; 9:70. [PMID: 21645344 PMCID: PMC3127780 DOI: 10.1186/1741-7015-9-70] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2010] [Accepted: 06/06/2011] [Indexed: 12/18/2022] Open
Abstract
The prevalence of obesity worldwide has dramatically increased during the last three decades. With obesity comes a variety of adverse health outcomes which are grouped under the umbrella of metabolic syndrome. The liver in particular seems to be significantly impacted by fat deposition in the presence of obesity. In this article we discuss several liver conditions which are directly affected by overweight and obese status, including non-alcoholic fatty liver disease, chronic infection with hepatitis C virus and post-liver transplant status. The deleterious effects of obesity on liver disease and overall health can be significantly impacted by a culture that fosters sustained nutritional improvement and regular physical activity. Here we summarize the current evidence supporting non-pharmacological, lifestyle interventions that lead to weight reduction, improved physical activity and better nutrition as part of the management and treatment of these liver conditions.
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Affiliation(s)
- Valerio Nobili
- Metabolic and Autoimmunity Liver Unit, Bambino Gesù Children's Hospital and Research Institute, S, Onofrio Square, 4, 00165 Rome, Italy.
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Moschen AR, Fritz T, Clouston AD, Rebhan I, Bauhofer O, Barrie HD, Powell EE, Kim SH, Dinarello CA, Bartenschlager R, Jonsson JR, Tilg H. Interleukin-32: a new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis. Hepatology 2011; 53:1819-29. [PMID: 21381070 DOI: 10.1002/hep.24285] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2010] [Accepted: 02/23/2011] [Indexed: 01/01/2023]
Abstract
UNLABELLED Interleukin 32 (IL-32) is a recently described proinflammatory cytokine that activates p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), thereby inducing proinflammatory cytokines such as IL-1β and tumor necrosis factor alpha (TNF-α). We investigated the role of IL-32 in patients with chronic hepatitis C virus (HCV) infection. Steady-state hepatic messenger RNA (mRNA) levels of IL-32 were determined in a cohort of 90 subjects; anti-IL-32 staining was used in a second cohort of 132 consecutive untreated chronic HCV patients. Correlations with histological features of steatosis, inflammation, and fibrosis were made. In vitro, endogenous IL-32 in monocytes and in the human hepatoma cell line Huh-7.5 were examined. The effects of IL-32-overexpression and IL-32-silencing on HCV replication were studied using HCV luciferase reporter viruses. There were highly significant positive associations between hepatic IL-32 mRNA expression and liver steatosis, inflammation, fibrosis, smooth muscle actin (SMA) area, and serum alanine aminotransferase (ALT) levels. IL-32 protein expression was positively associated with portal inflammation, SMA area, and ALT. In vitro, IL-1β and TNF-α significantly induced IL-32 expression in human Huh-7.5 cells. Alone, stimulation with interferon alpha (IFN-α) did not induce IL-32 expression in Huh-7.5. However, IFN-α exerted a significant additive effect on TNF-α-induced but not IL-1β-induced IL-32 expression, particularly in CD14+ monocytes. This effect was dependent both on NF-κB and Jak/STAT signaling. Viral infection of Huh-7.5 cells resulted in a significant (11-fold) induction of IL-32 mRNA expression. However, modulation of IL-32 in Huh-7.5 cells by overexpression or silencing did not influence HCV virus replication as determined by luciferase assays. CONCLUSION IL-32 is a novel proinflammatory cytokine involved in HCV-associated liver inflammation/fibrosis. IL-32 is expressed by human hepatocytes and hepatoma cells and its expression is regulated by proinflammatory stimuli.
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Affiliation(s)
- Alexander R Moschen
- Christian Doppler Research Laboratory for Gut Inflammation, Innsbruck Medical University, Innsbruck, Austria
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Negro F. Mechanisms of hepatitis C virus-related insulin resistance. Clin Res Hepatol Gastroenterol 2011; 35:358-63. [PMID: 21354385 DOI: 10.1016/j.clinre.2011.01.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2011] [Accepted: 01/17/2011] [Indexed: 02/04/2023]
Abstract
The hepatitis C virus (HCV) infection has been shown to have direct and/or indirect effects on glucose metabolism, leading to insulin resistance and, in predisposed individuals, type 2 diabetes. This is supported by several experimental, clinical and epidemiological data. The detailed molecular events leading to insulin resistance in HCV-infected patients are unclear. HCV infects primarily the liver and, to a very minor extent, mononuclear cells. Direct interactions between HCV products and the hepatocyte insulin signaling pathway have been reported by several authors. However, recent evidence supports the existence of a significant extrahepatic component of HCV-induced insulin resistance. Thus, the molecular pathogenesis of glucose metabolism disturbances observed in hepatitis C is much more complex than expected. The clinical management of such condition remains empirical.
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Affiliation(s)
- Francesco Negro
- Departments of Internal Medicine and Pathology and Immunology, Divisions of Gastroenterology and hepatology and of Clinical pathology, University Hospitals, University of Geneva Medical Center, 1, rue Michel-Servet, 1205 Geneva, Switzerland.
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Li L, Yang Y, Yang G, Lu C, Yang M, Liu H, Zong H. The role of JAZF1 on lipid metabolism and related genes in vitro. Metabolism 2011; 60:523-30. [PMID: 20580384 DOI: 10.1016/j.metabol.2010.04.021] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2010] [Revised: 04/09/2010] [Accepted: 04/23/2010] [Indexed: 12/11/2022]
Abstract
JAZF1 is a novel gene that is associated with diabetes mellitus and prostate cancer according to genomewide association studies; however, little is known about the function of this gene in regulating metabolism. In the present study, we have shown the expression of JAZF1 in various mouse tissues. To elucidate its role in metabolism, we investigated the influence of an overexpression of JAZF1 on 3T3-L1 adipose cells and hepatoma carcinoma Hepa1-6 cells that represent target tissues for diabetes and insulin resistance. In both cells, JAZF1 overexpression led to a substantial reduction in the expression of acetyl-coenzyme A carboxylase, fatty acid synthetase, and sterol regulatory element-binding protein 1 messenger RNA (mRNA). The level of hormone-sensitive lipase mRNA significantly increased. The expression of JAZF1 in 3T3-L1 adipocyte exhibited suppressive effects on lipid accumulation and decreased droplet size. In addition, the transcription for glucose transport 1 was significantly higher than the control in the Hepa1-6 cell line; but it was not significantly different in 3T3-L1. These results showed that JAZF1 in adipocytes and liver cells reduces lipid synthesis and increases lipolysis mainly by down-regulating the levels of sterol regulatory element-binding protein 1, acetyl-coenzyme A carboxylase, and fatty acid synthetase mRNA expression and by increasing hormone-sensitive lipase mRNA expression. Because it had an effect on the decrease of the maturation of lipid droplets and fat storage, we speculate that JAZF1 might represent a potential target against diabetes and obesity.
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Affiliation(s)
- Ling Li
- The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education and Department of Clinical Biochemistry, Chongqing Medical University, 400016 Chongqing, China.
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Delgado-Borrego A, Kamegaya Y, Jordan SH, Agrawal S, Valim C, Chung RT. HCV synergizes with body weight in the promotion of insulin resistance. J Viral Hepat 2011; 18:135-41. [PMID: 20497310 PMCID: PMC3806633 DOI: 10.1111/j.1365-2893.2010.01291.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) infection appears to contribute to the development of insulin resistance (IR). Among the multiple determinants of IR, body mass index (BMI) is the most important. We investigated the contribution of HCV to BMI-associated IR using a transgenic mouse model expressing HCV core protein. Eight transgenic and five nontransgenic littermate controls were evaluated. Glucose and insulin tolerance tests (ITT) were performed on two separate occasions. Multivariate linear mixed modelling was used to evaluate and compare the effect of weight on IR between HCV core transgenic and nontransgenic controls. There were no statistically significant differences in glucose or ITT (P = 0.58 and P = 0.59, respectively) between the two groups, and no difference in median weights between transgenic and control mice (P = 0.11). However, there was greater variance in the distributions of Tg when compared to nontransgenic mice for both glucose and insulin tolerance. When evaluating this closely, a differential contribution of weight to IR curves between these groups was noted (P = 0.05). Among nontransgenic mice, IR curves for mice of different weights were comparable, however, for transgenic mice, higher weights resulted in larger levels of IR curves with slower decay. In all animals, steatosis was absent or minimal. We conclude that weight has a greater effect on IR in HCV core expressing transgenic mice than littermate controls. HCV therefore synergizes with weight in the promotion of IR. Steatosis was not a prerequisite for the development of IR, implying that HCV's effects on IR may be independent of steatosis.
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Affiliation(s)
- Aymin Delgado-Borrego
- Gastroenterology and Nutrition Unit, Department of Medicine, Children’s Hospital Boston,Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital
| | - Yoshitaka Kamegaya
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital
| | - Sergio H. Jordan
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital
| | - Saurabh Agrawal
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital
| | - Clarissa Valim
- Division of Biostatistics, Clinical Research Program, Children’s Hospital Boston
| | - Raymond T. Chung
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital,Address correspondence to: Raymond T. Chung, M.D., Massachusetts General Hospital, 55 Fruit St. GI Unit, Warren 1007, Boston, MA 02114, Telephone: (617) 724-7562. Fax: (617) 643-0446,
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Cheung O, Sterling RK, Salvatori J, Williams K, Hubbard S, Luketic VA, Stravitz TR, Sanyal AJ, Contos MJ, Mills S, Shiffman ML. Mild alcohol consumption is not associated with increased fibrosis in patients with chronic hepatitis C. J Clin Gastroenterol 2011; 45:76-82. [PMID: 20818236 DOI: 10.1097/mcg.0b013e3181e12511] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Excessive alcohol consumption is associated with an increased risk for fibrosis progression and cirrhosis in patients with chronic hepatitis C virus (HCV) infection. However, the impact of mild-moderate alcohol use on the severity of liver fibrosis is unclear. GOALS The objective of this retrospective study was to assess the impact of mild alcohol consumption on liver fibrosis in patients with chronic HCV. STUDY 857 patients with well-characterized chronic HCV were enrolled. All underwent liver biopsy to assess hepatic fibrosis. The duration of HCV infection was determined by detailed questionnaires and personal interviews. Alcohol use history was estimated by the Skinner Alcohol Examination Questionnaire. Mild alcohol use was defined as 1 to 3 alcoholic beverages/day (<30 grams/d). Participants were divided into 4 groups based on their average lifetime daily alcohol consumption (essentially none, <1, 1 to 3 or >3 drinks/d) and into quartiles based on their presumed duration of HCV infection (<23, 23 to 31, 31 to 38, or >38 y). RESULTS Mean alcohol consumption was 2.7 drinks/d; mean duration of HCV infection was 29 years. Daily alcohol consumption was not significantly higher among participants with advanced fibrosis (bridging fibrosis or cirrhosis) when compared with those with none or portal fibrosis (3.2 vs. 2.2 drinks/d, respectively, P=NS). The degree of fibrosis increased significantly with the duration of HCV infection (P<0.0001) and was independent of mild-moderate alcohol consumption. CONCLUSIONS Mild alcohol use does not seem to adversely affect the severity of fibrosis in patients with chronic HCV.
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Affiliation(s)
- Onpan Cheung
- Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA, USA
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Iwasa M, Hara N, Iwata K, Ishidome M, Sugimoto R, Tanaka H, Fujita N, Kobayashi Y, Takei Y. Restriction of calorie and iron intake results in reduction of visceral fat and serum alanine aminotransferase and ferritin levels in patients with chronic liver disease. Hepatol Res 2010; 40:1188-94. [PMID: 20880065 DOI: 10.1111/j.1872-034x.2010.00724.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM To clarify the impact of visceral fat on chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and hepatitis C, we investigated the effects of lifestyle modifications on the amount of visceral fat, liver biochemistry and serum ferritin levels in patients with liver disease. METHODS Eighty-two patients (NAFLD, n = 37; hepatitis C, n = 45) were advised to adopt lifestyle modifications, including dietary changes and exercise, and these were maintained for 6 months. Bodyweight, percentage of body fat, visceral fat area (VFA) and serum alanine aminotransferase (ALT) and ferritin were measured before and after intervention. RESULTS In NAFLD, the mean VFA of 134.5 cm(2) was significantly reduced to 125.3 cm(2) after 6 months (P < 0.001). ALT levels improved significantly between the values measured before and after intervention (P = 0.039). The VFA prior to intervention was 100 cm(2) in hepatitis C patients and it was reduced significantly after 6 months to 95.6 cm(2) (P < 0.001). ALT levels also improved significantly in the hepatitis C patients (P < 0.001). The serum ferritin levels also reduced in these patients. Improvements in serum ALT and ferritin levels correlated with the amount of visceral fat reduction in both groups (P = 0.046, P = 0.008, respectively). CONCLUSION These findings demonstrate that restriction of calorie and iron intake results in reduction of visceral fat, liver enzymes and ferritin in patients with chronic liver disease. Visceral fat may be a central target for future interventions, not only in NAFLD but also in hepatitis C.
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Affiliation(s)
- Motoh Iwasa
- Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Sciences, Institute of Medical Science, Mie University Graduate School of Medicine Division of Dietary Service, Mie University School Hospital, Tsu, Japan
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