title: In overweight patients with chronic hepatitis C, circulating insulin is associated with hepatic fibrosis: implications for therapy.
abstract: OBJECTIVE
  Host factors such as increased body mass index (BMI) and genotype-specific viral factors contribute to the development of steatosis in patients with chronic hepatitis C (HCV). We hypothesized that host metabolic factors associated with increased BMI may play a role in disease progression.
  
  
  METHODS
  Fasting serum was collected from 160 patients with chronic HCV at the time of liver biopsy and 45 age, gender and BMI matched controls, and assessed for levels of insulin, c-peptide and leptin.
  
  
  RESULTS
  Patients with viral genotype 3 had more severe steatosis (P=0.0001) and developed stages 1 and 2 fibrosis at a younger age (P<0.05) than patients with genotype 1. For both genotypes, overweight patients had significantly more steatosis and increased insulin and leptin levels. In contrast to lean patients, there was a statistically significant increase in circulating insulin levels with increasing fibrosis in overweight patients with chronic HCV (P=0.03). Following multivariate analysis, insulin was independently associated with fibrosis (P=0.046) but not inflammation (P=0.83). There was no association between serum leptin levels and stage of fibrosis.
  
  
  CONCLUSIONS
  Increasing circulating insulin levels may be a factor responsible for the association between BMI and fibrosis in patients with HCV, irrespective of viral genotype.
authors.affiliation: School of Medicine, Southern Clinical Division, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Brisbane, Qld 4102, Australia.
authors.forename: Ingrid J
authors.initials: IJ
authors.lastname: Hickman
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Powell
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Prins
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Clouston
authors.forename: Susan
authors.initials: S
authors.lastname: Ash
authors.forename: David M
authors.initials: DM
authors.lastname: Purdie
authors.forename: Julie R
authors.initials: JR
authors.lastname: Jonsson
mesh_terms: D000328:Adult; D015992:Body Mass Index; D005234:Fatty Liver / Q000150:complications / Q000378:metabolism / Q000821:virology; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007328:Insulin / Q000097:blood*; D020738:Leptin / Q000097:blood; D008103:Liver Cirrhosis / Q000150:complications* / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000378:metabolism / Q000628:therapy
chemical_list: D007328:Insulin; D020738:Leptin