Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis C and in the response to antiviral therapy.
OBJECTIVE
To assess whether insulin resistance is associated with liver fibrosis in a group of patients with chronic hepatitis C virus (HCV) infection and whether there were any differences in insulin resistance between Asians and the indigenous Caucasian population. Secondly, to assess whether insulin resistance is associated with sustained virological response to antiviral therapy.


METHODS
We determined insulin resistance in 59 (30 Caucasians; 29 Asians) consecutive patients with HCV prior to starting antiviral therapy. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). The relationship between insulin resistance and biochemical, virological, and histological data together with response to antiviral therapy was assessed.


RESULTS
In multivariable analyses, insulin resistance as measured using the HOMA-IR model correlated positively with the stage of fibrosis, with higher degrees of insulin resistance in those with greater degrees of fibrosis (p < 0.001). This significant relationship remained even after excluding cirrhotic patients, or after adjusting for other factors associated with fibrosis in univariable analyses. Insulin resistance was significantly higher in Asians than Caucasians (p= 0.004). Around half (55.6%) of patients completing a course of antiviral treatment had a sustained virological response. Multivariable logistic regression identified HCV genotype 3, lower fasting glucose levels, and lower aspartate transaminase (AST) levels as being associated with a higher odds of a sustained virological response. After adjusting for these variables, Asian ethnicity, higher fasting insulin levels, and higher HOMA-IR levels were all associated with a poorer virological response to therapy.


CONCLUSIONS
Insulin resistance contributes to liver fibrosis in chronic HCV infection; this relationship is not genotypic specific. Asian patients had higher insulin resistance than Caucasians. Insulin resistance is also an important predictor of sustained response to antiviral therapy.
Hepatobiliary Group, Institute of Cellular and Molecular Science, Queen Mary's School of Medicine and Dentistry, London, United Kingdom.
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R
D'Souza
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Sabin
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Foster
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000208:ethnology / Q000503:physiopathology*; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D044465:White People
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a