title: Factors associated with the progression of fibrosis on liver biopsy in Alaska Native and American Indian persons with chronic hepatitis C.
abstract: BACKGROUND
  Various factors influence the development and rate of fibrosis progression in chronic hepatitis C virus (HCV) infection.
  
  
  OBJECTIVE
  To examine factors associated with fibrosis in a longterm outcomes study of Alaska Native/American Indian persons who underwent liver biopsy, and to examine the rate of fibrosis progression in persons with subsequent biopsies.
  
  
  METHODS
  A cross-sectional analysis of the demographic, inflammatory and viral characteristics of persons undergoing liver biopsy compared individuals with early (Ishak fibrosis score of lower than 3) with those with advanced (Ishak score of 3 or greater) fibrosis. Persons who underwent two or more biopsies were analyzed for factors associated with fibrosis progression.
  
  
  RESULTS
  Of 253 HCV RNA-positive persons who underwent at least one liver biopsy, 76 (30%) had advanced fibrosis. On multivariate analysis, a Knodell histological activity index score of 10 to 14 and an alpha-fetoprotein level of 8 ng/mL or higher were found to be independent predictors of advanced liver fibrosis (P<0.0001 for each). When surrogate markers of liver inflammation (alanine aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio and alpha-fetoprotein) were removed from the model, type 2 diabetes mellitus (P=0.001), steatosis (P=0.03) and duration of HCV infection by 10-year intervals (P=0.02) were associated with advanced fibrosis. Among 52 persons who underwent two or more biopsies a mean of 6.2 years apart, the mean Ishak fibrosis score increased between biopsies (P=0.002), with progression associated with older age at initial biopsy and HCV risk factors.
  
  
  CONCLUSIONS
  The presence of type 2 diabetes mellitus, steatosis and duration of HCV infection were independent predictors of advanced fibrosis in the present cohort, with significant fibrosis progression demonstrated in persons who underwent serial biopsies.
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium Liver Disease & Hepatitis Program, Anchorage, Alaska 99508, USA. slivings@anthc.org
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Livingston
authors.forename: Heike
authors.initials: H
authors.lastname: Deubner
authors.forename: Dana L
authors.initials: DL
authors.lastname: Bruden
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McMahon
authors.forename: Chriss E
authors.initials: CE
authors.lastname: Homan
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Townshend-Bulson
authors.forename: Michael G
authors.initials: MG
authors.lastname: Bruce
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Hennessy
authors.forename: James L
authors.initials: JL
authors.lastname: Williams
authors.forename: David R
authors.initials: DR
authors.lastname: Gretch
mesh_terms: D000328:Adult; D000413:Alaska / Q000453:epidemiology; D001706:Biopsy; D016009:Chi-Square Distribution; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000208:ethnology / Q000473:pathology; D018450:Disease Progression; D005234:Fatty Liver / Q000453:epidemiology / Q000208:ethnology / Q000473:pathology; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000453:epidemiology / Q000208:ethnology; D006801:Humans; D007198:Indians, North American; D004930:Inuit; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000208:ethnology / Q000473:pathology* / Q000821:virology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D018709:Statistics, Nonparametric