title: Risk factors for development of hepatocellular carcinoma among Australians with hepatitis C: a case-control study.
abstract: BACKGROUND
  Older patients with cirrhosis due to hepatitis C are at risk of developing hepatocellular carcinoma (HCC), but additional risk factors may vary between countries.
  
  
  OBJECTIVE
  In the present study, we sought to identify additional risk factors for HCC among a cohort of Australian patients with chronic hepatitis C.
  
  
  METHODS
  Case-control study of patients with advanced fibrosis stage hepatitis C who developed HCC during five-year follow up at a referral liver clinic. Cases were compared to twice the number of age-matched patients with chronic hepatitis C of similar fibrotic severity who did not develop HCC over a similar interval, using conditional logistic regression analysis (CLRA) and multivariate analysis. The main outcome measures were demographic and disease-related variables at first presentation in relation to the development of HCC.
  
  
  RESULTS
  HCC developed in 17 cases, an annual incidence among those considered to be at risk of 2%. The duration of follow up since first assessment was comparable among the cases and 34 selected age-matched controls (4.1 and 5.2 years respectively, p=0.5). Cases were more often male (p=0.03), born in Asia (p=0.05), and had poorer liver function as indicated by serum albumin concentration (p=0.02). Anti-hepatitis B core-antibody (anti-HBc) was detected in 59% (ten/17) of cases, compared to 21% (seven/34) of the controls (p=0.01). No patient with a sustained response to interferon developed HCC during follow up. There were no significant differences in the mode of HCV transmission, HCV genotype, alcohol exposure, serum bilirubin level or prothrombin time between the cases and the controls. Although the data set was small, multivariate CLR analysis identified serum albumin < or = 35 g/L and anti-HBc positivity to be independent risk factors for development of HCC.
  
  
  CONCLUSIONS
  Among older Australian patients (over the age of 40 years) with advanced fibrosis stage hepatitis C, the annual incidence of HCC is about 2%. Those who have low serum albumin and evidence of previous exposure to hepatitis B virus (anti-HBc positivity) appear to have the highest risk of developing HCC during follow up, but males and those born in Asia could also be at increased risk.
authors.affiliation: University of Sydney at Westmead Hospital, Department of Gastroenterology, Westmead Hospital, NSW.
authors.forename: U
authors.initials: U
authors.lastname: Dutta
authors.forename: K
authors.initials: K
authors.lastname: Byth
authors.forename: J
authors.initials: J
authors.lastname: Kench
authors.forename: M H
authors.initials: MH
authors.lastname: Khan
authors.forename: S A
authors.initials: SA
authors.lastname: Coverdale
authors.forename: M
authors.initials: M
authors.lastname: Weltman
authors.forename: R
authors.initials: R
authors.lastname: Lin
authors.forename: C
authors.initials: C
authors.lastname: Liddle
authors.forename: G C
authors.initials: GC
authors.lastname: Farrell
mesh_terms: D000368:Aged; D001315:Australia / Q000453:epidemiology; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000453:epidemiology*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors