November 21, 2010

J Viral Hepat. 2010 Nov 10. doi: 10.1111/j.1365-2893.2010.01394.x. [Epub ahead of print]

Ramcharran D, Wahed AS, Conjeevaram HS, Evans RW, Wang T, Belle SH, Yee LJ.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Division of Gastroenterology, School of Medicine, University of Michigan, Ann Arbor, MI, USA Department of Infectious Disease and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Division of Infectious Diseases, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Abstract

Summary.  In patients with chronic hepatitis C virus (HCV) infection, steatosis and fibrosis have been shown to be inversely associated with total cholesterol (TC) and low-density lipoprotein cholesterol. Steatosis and fibrosis have also been found to be associated with triglyceride (TG) levels; though, the direction of the relationship is inconsistent across studies. The objective of this study was to assess whether viral level and histological factors are associated with the serum lipid profile in a treatment-naïve cohort with chronic HCV genotype 1 infection. Participants were from the prospective Study of Viral Resistance to Antiviral Therapy (Virahep-C). Fasting lipid profiles were analysed for 160 African Americans and 170 Caucasian Americans. Linear regression was used to evaluate associations of each lipid with viral load and liver disease. TG levels were significantly and directly associated with HCV levels (P = 0.0034) and steatosis (P < 0.0001). Other lipid parameters were significantly lower in those with fibrosis [HDLc (P = 0.001) and TC levels (P = 0.004)] than in those without fibrosis. In patients with HCV genotype 1 infection, more severe liver disease was associated with lower lipid levels, with the exception of TG levels that were directly related to steatosis. The direct relationship between viral load and TG levels is consistent with proposed the mechanisms of very low density lipoprotein/HCV particle secretion. In contrast, the direct relationship between TG level and steatosis is inconsistent with posited mechanisms of HCV-induced steatosis, a possible reflection of HCV genotype 1 infection and a metabolic aetiology of steatosis.

© 2010 Blackwell Publishing Ltd.

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Gastroenterology. 2010 Nov 8. [Epub ahead of print]

Conjeevaram HS, Wahed AS, Afdhal N, Howell CD, Everhart JE, Hoofnagle JH; Virahep-C Study Group.

University of Michigan, Ann Arbor, MI.

Abstract

BACKGROUND & AIMS: Chronic hepatitis C is associated with an increased prevalence of insulin resistance, which might result from liver disease, metabolic factors, or the hepatitis C virus (HCV) itself. The effect of antiviral treatment on insulin sensitivity is not well known. We evaluated changes in insulin resistance and weight in patients with hepatitis C during and after peginterferon and ribavirin therapy.

METHODS: Virahep-C was a prospective, multi-center study of a 48-week course of combination antiviral therapy in patients infected with HCV genotype 1. Insulin resistance was estimated by the homeostasis model assessment index (HOMA2-IR) based on fasting glucose and insulin levels.

RESULTS: Among 341 patients, 40% had insulin resistance (HOMA2-IR > 2.0). The presence of insulin resistance was associated with increasing age, body mass index, (BMI) and fibrosis stage. Among patients with insulin resistance at the start of the trial, median decreases in HOMA2-IR values during treatment were 0.74 at 24 weeks and 0.89 at 48 weeks, whereas BMI decreased by 1.2 and 2.2 kg/m(2) at the same timepoints ( P <0.001 for all). At follow-up, HOMA2-IR and BMI levels returned toward baseline values in patients that did not respond or relapsed, but HOMA2-IR values remained significantly lower in patients with sustained virological response (SVR) ( P <0.001), despite increases in BMI.

CONCLUSIONS: In patients with HCV genotype 1 infections, therapy with peginterferon and ribavirin is associated with decreases in body weight and insulin resistance. Among patients with insulin resistance before treatment, resolution of HCV infection results in sustained improvements in the homeostasis model assessment index, so HCV could have a direct role in the pathogenesis of insulin resistance. All studies published in Gastroenterology are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.

Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID: 21070775 [PubMed - as supplied by publisher]

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Eur J Gastroenterol Hepatol. 2010 Nov 12. [Epub ahead of print]

Andersen ES, Moessner BK, Christensen PB, Kjær M, Krarup H, Lillevang S, Weis N.

aDepartments of Infectious Diseases, Hvidovre bInfectious Diseases cHepatology, Copenhagen University Hospital, Rigshospitalet dDepartments of Infectious Diseases eClinical Immunology, Odense University Hospital fUniversity of Copenhagen, Faculty of Health Sciences, Copenhagen gDepartment of Clinical Biochemistry, Aalborg University Hospital, Denmark.

Abstract

OBJECTIVE: Transient elastography (TE) is a noninvasive and well validated method for measurement of liver stiffness. The aim of this study was to use TE to evaluate whether patients with sustained virological response (SVR) have lower liver stiffness than patients with non-SVR after treatment for chronic hepatitis C (CHC).

METHODS: Patients with CHC, who had undergone liver biopsy before treatment with pegylated interferon and ribavirin, were included from four clinical centres in Denmark. All patients were examined with TE and had a blood test taken for hepatitis C virus-virus detection and analysis of alanine aminotransferase, platelet counts and hyaluronic acid.

RESULTS: For 110 (92%) of the 120 patients included, it was possible to obtain a successful measurement of liver stiffness. Of these, 71 (64.5%) had achieved SVR. Median follow-up time was 47 months. Patients with pretreatment minimal fibrosis (F0/F1) in their liver biopsy had median liver stiffness of 5.3 kPa for SVR versus 6.1 kPa for non-SVR (P=0.56). Patients with pretreatment moderate fibrosis (F2/F3) had median liver stiffness of 5.4 kPa for SVR versus 9.4 kPa for non-SVR (P<0.001). Median liver stiffness for patients with pretreatment cirrhosis (F4) was 6.8 kPa for SVR versus 24 kPa for non-SVR (P<0.001).

CONCLUSIONS: Examination with TE 4 years after treatment shows that patients with CHC, who have achieved SVR, have significantly lower liver stiffness than patients with non-SVR. This indicates that histological liver outcome improves during the first year after the treatment for CHC.

PMID: 21079513 [PubMed - as supplied by publisher]

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Clin Gastroenterol Hepatol. 2010 Sep 24. [Epub ahead of print]

Jacobson IM, Cacoub P, Dal Maso L, Harrison SA, Younossi ZM.

Division of Gastroenterology and Hepatology, Center for the Study of Hepatitis C, Joan and Sanford I. Weill Medical College of Cornell University, New York, New York.

Abstract

In addition to its effects in the liver, chronic hepatitis C virus (HCV) infection can have serious consequences for other organ systems. Extrahepatic manifestations include mixed cryoglobulinemia (MC) vasculitis, lymphoproliferative disorders, renal disease, insulin resistance, type 2 diabetes, sicca syndrome, rheumatoid arthritis-like polyarthritis, and autoantibody production; reductions in quality of life involve fatigue, depression, and cognitive impairment. MC vasculitis, certain types of lymphoma, insulin resistance, and cognitive function appear to respond to anti-HCV therapy. However, treatments for HCV and other biopsychosocial factors can reduce quality of life and complicate management. HCV treatment has a high overall cost that increases when extrahepatic manifestations are considered. HCV appears to have a role in the pathogenesis of MC vasculitis, certain types of lymphoma, and insulin resistance. Clinicians who treat patients with HCV infections should be aware of potential extrahepatic manifestations and how these can impact and alter management of their patients.

Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID: 20870037 [PubMed - as supplied by publisher

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