Risk factors for development of hepatocellular carcinoma among Australianswith hepatitis C: a case-control study

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. Aim: In the present study, we sought to identify additional risk factors fo r HCC among a cohort of Australian patients with chronic hepatitis C. Methods: Case-control study of patients with advanced fibrosis stage hepati tis C who developed HCC during five-year follow up at a referral liver clin ic. Cases were compared to twice the number of age-matched patients with ch ronic 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 d isease-related variables at first presentation in relation to the developme nt of HCC. Results: HCC developed in 17 cases, an annual incidence among those conside red to be at risk of 2%. The duration of follow up since first assessment w as 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 album in concentration (p=0.02). Anti-hepatitis B core antibody (anti-HBc) was de tected 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 pro thrombin time between the cases and the controls. Although the data set was small, multivariate CLR analysis identified serum albumin less than or equ al to 35 g/L and anti-HBc positivity to be independent risk factors for dev elopment of HCC. Conclusions: Among older Australian patients (over the age of 40 years) wit h 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 als o be at increased risk.