title: Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C.
abstract: BACKGROUND
  Insulin resistance is a frequent feature of chronic hepatitis C. Whether insulin resistance could be the cause or consequence of steatosis and fibrosis is unknown. The ability of HCV genotype 3 to promote steatosis by itself provides an unique opportunity to answer this question.
  
  
  OBJECTIVE
  The aim of the present study was to assess the relationships between insulin resistance, steatosis, and fibrosis according to genotype in 141 non-diabetic patients with biopsy proven non-cirrhotic chronic hepatitis C.
  
  
  METHODS
  All patients had fasting serum glycaemia and insulinaemia measurements. Insulin resistance was evaluated using the homeostasis model assessment (HOMA IR) method. Liver steatosis was determined according to hepatitis C virus genotype (1 or 3). Logistic regression and multivariate regression analysis were used to identify variables independently associated with insulin resistance, fatty liver, and fibrosis.
  
  
  RESULTS
  Although steatosis and fibrosis were more severe in genotype 3 patients, median HOMA IR was significantly higher in patients with genotype 1 related steatosis than in those with genotype 3 related steatosis (2.1 v 1; p = 0.001). Independent risk factors for steatosis were insulin resistance in genotype 1 patients (p = 0.001) and viral load in genotype 3 patients (p = 0.003). Among genotype 1 patients, independent parameters associated with insulin resistance were age (p = 0.04) and steatosis (p = 0.004). Steatosis was associated with more severe fibrosis whatever the genotype (p = 0.002). Among genotype 1 patients, although there was a significant relationship between circulating insulin level and fibrosis stage (p = 0.006), only steatosis and inflammatory score were independently associated with fibrosis.
  
  
  CONCLUSIONS
  This study shows that insulin resistance is the cause rather than the consequence of steatosis and fibrosis in genotype 1 patients and that increased circulating insulin is a risk factor for fibrosis through insulin resistance induced steatosis.
authors.affiliation: Service d'Hépatologie, Hôpital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, 75571 Paris cedex 12, France.
authors.forename: L
authors.initials: L
authors.lastname: Fartoux
authors.forename: A
authors.initials: A
authors.lastname: Poujol-Robert
authors.forename: J
authors.initials: J
authors.lastname: Guéchot
authors.forename: D
authors.initials: D
authors.lastname: Wendum
authors.forename: R
authors.initials: R
authors.lastname: Poupon
authors.forename: L
authors.initials: L
authors.lastname: Serfaty
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D005234:Fatty Liver / Q000097:blood / Q000503:physiopathology / Q000821:virology*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008103:Liver Cirrhosis / Q000097:blood / Q000503:physiopathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D007328:Insulin