Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3

• Published in: Gut Vol. 61; no. 1; pp. 128 - 134
• Main Authors: Thompson, Alexander J, Patel, Keyur, Chuang, Wan-Long, Lawitz, Eric J, Rodriguez-Torres, Maribel, Rustgi, Vinod K, Flisiak, Robert, Pianko, Stephen, Diago, Moises, Arora, Sanjeev, Foster, Graham R, Torbenson, Michael, Benhamou, Yves, Nelson, David R, Sulkowski, Mark S, Zeuzem, Stefan, Pulkstenis, Erik, Subramanian, G Mani, McHutchison, John G
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.01.2012; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: ACHIEVE; Adult; albinterferon alpha-2b; Albumins - therapeutic use; Antiviral Agents - therapeutic use; Biological and medical sciences; diabetes mellitus; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; HCV; Hepacivirus - genetics; Hepacivirus - isolation & purification; Hepatitis C virus; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Human viral diseases; Humans; Infectious diseases; Insulin Resistance; interferon; Interferon-alpha - therapeutic use; Linear Models; Liver cirrhosis; Logistic Models; Male; Medical sciences; Metabolic disorders; Mortality; Multivariate Analysis; Polyethylene Glycols - therapeutic use; Recombinant Proteins - therapeutic use; Rodents; sustained virologic response; Treatment Outcome; Viral diseases; Viral hepatitis; Viral Load; California; Endocrinopathy; Typing; Metabolic diseases; Hepatic disease; Genotype; Clearance; Infection; Target tissue resistance; Microbiological investigation; Viral disease; Gastroenterology; Digestive diseases; Insulin resistance; Viral hepatitis C
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gut.2010.236158

ObjectivesGenotype-specific associations between hepatitis C virus (HCV) and insulin resistance (IR) have been described, but a causal relationship remains unclear. This study investigated the association between a sustained virological response (SVR) and IR after chronic HCV therapy.Methods2255 treatment-naive patients with chronic HCV genotype 1 or 2/3 were enrolled in two phase 3 trials of albinterferon alpha-2b versus pegylated interferon alpha-2a for 48 or 24 weeks, respectively. IR was measured before treatment and 12 weeks after treatment using homeostasis model assessment (HOMA)-IR.ResultsPaired HOMA-IR measurements were available in 1038 non-diabetic patients (497 with genotype 1; 541 with genotype 2/3). At baseline the prevalence of HOMA-IR >3 was greater in patients with genotype 1 than 2/3 (33% vs 27%; p=0.048). There was a significant reduction in the prevalence of IR in patients with genotype 1 achieving SVR (δ 10%; p<0.001), but not in genotype 1 non-responders or those with genotype 2/3. Multivariate analysis indicated that SVR was associated with a significant reduction in mean HOMA-IR in patients with genotype 1 (p=0.004), but not in those with genotype 2/3, which was independent of body mass index, alanine transaminase, γ-glutamyl transpeptidase and lipid level changes.ConclusionsSVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but not in those with genotype 2/3. Genotype 1 may have a direct effect on the development of IR, independent of host metabolic factors, and may be partially reversed by viral eradication.