Changes in insulin sensitivity and body weight during and after peginterferon and ribavirin therapy for hepatitis C.
OBJECTIVE
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, multicenter study of a 48-week course of combination antiviral therapy in patients infected with HCV genotype 1. Insulin resistance (IR) 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 at the same time points (P < .001 for all). At follow-up, HOMA2-IR and BMI levels returned toward baseline values in patients who did not respond or relapsed, but HOMA2-IR values remained significantly lower in patients with sustained virologic response (SVR) (P < .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 HOMA-IR index, suggesting that HCV could have a direct role in the pathogenesis of insulin resistance.
Division of Gastroenterology, The University of Michigan, 3912 Taubman Center, 1500 East Medical Center Dr, Ann Arbor, Michigan 48109, USA. omsairam@med.umich.edu
Hari S
HS
Conjeevaram
Abdus S
AS
Wahed
Nezam
N
Afdhal
Charles D
CD
Howell
James E
JE
Everhart
Jay H
JH
Hoofnagle
D000328:Adult; D000367:Age Factors; D000998:Antiviral Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D007333:Insulin Resistance; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D015337:Multicenter Studies as Topic; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a