Risk and predictors of hepatocellular carcinoma for chronic hepatitis B patients with newly developed cirrhosis

Background and Aims: Most studies on risk predictors of hepatocellular carcinoma (HCC) among cirrhotic chronic hepatitis B patients do not confirm the date at cirrhosis diagnosis. We examined HCC risk and predictors in chronic hepatitis B patients with newly diagnosed cirrhosis. Methods: 4155 HBsAg seropositive participants were followed every 6–12 months with seromarker testing. Cirrhosis was ascertained through abdominal ultrasonography and computerized linkage with national health insurance profiles. Predictors included in Cox proportional hazards models were age, HBeAg serostatus, serum levels of HBsAg, alanine aminotransferase (ALT), alpha-fetoprotein (AFP), and ALDH2 rs671 genotypes. Results: A total of 301 patients developed cirrhosis, 76 of whom later developed HCC after 2462 person-years, showing an average annual incidence of 3.1%. The 15-year cumulative HCC risk among cirrhotics was 39.8% with a lifetime (30–80 years old) HCC risk of 78.5%. The adjusted HR's (95% CI, P-value) were 14.26 (3.17–64.08, P = 0.0005) for age at cirrhosis diagnosis of ≥60 years (vs 30–39 years), 2.85 (1.49–5.46, P = 0.0015) for HBeAg seropositivity (vs HBeAg seronegativity with HBsAg levels <1000 IU/mL), 0.35 (0.20–0.59, P < 0.0001) for AA/AG genotypes of rs671 (vs GG genotype), 3.68 (1.70–7.99, P = 0.0010) for ALT levels >45 U/L (vs <15 U/L), 3.52 (1.78–6.93, P = 0.0003) for AFP levels >20 ng/mL (vs <10 ng/mL), and 2.64 (1.38–5.07, P = 0.0035) for HBsAg levels ≥1000 IU/mL (vs <1000 IU/mL among HBeAg seronegatives). Conclusions: Older age, GG genotype of ALDH2 rs671, HBeAg seropositivity, and elevated serum levels of ALT, AFP, and HBsAg at cirrhosis diagnosis were HCC risk predictors in cirrhotic chronic hepatitis B patients.