The risk of hepatocellular carcinoma among chronic hepatitis B virus-infected patients outside current treatment criteria.

We assessed the incidence of hepatocellular carcinoma (HCC) in those outside of current treatment recommendations and risk factors associated with HCC development. A multi-centre, retrospective cohort of 3624 patients who were monitored without antiviral treatment was analysed. Incident HCC risk according to the Asian Pacific Association for the study of the Liver (APASL), the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of the Liver (EASL) treatment recommendations was assessed. A risk score was developed using independent factors associated with HCC development among patients who were outside current treatment criteria. During a median follow-up of 4.6 years, incident HCC was diagnosed in 161 (4.4%) patients. The proportions of patients who developed HCC outside treatment recommendation according to APASL, AASLD and EASL criteria were 64.0%, 46.0% and 33.5%, respectively. The 5-year cumulative HCC incidence rate was 13.9% for cirrhotic patients with low-level viremia and 6.1 ~ 7.3% for chronic hepatitis patients with elevated HBV DNA levels plus mildly elevated alanine aminotransferase levels. Among patients who were outside treatment recommendation, age, sex, hepatitis B e antigen, cirrhosis, alanine aminotransferase and platelet levels were independent factors associated with HCC development. When these factors were used to calculate the risk score for each patient, those with a score ≥8 had a higher HCC incidence rate (14.3% at 5-year), although they were currently outside treatment recommendations. Thus, HCC was observed among patients who were outside current treatment criteria indicating that careful monitoring for HCC and efforts to identify patients at risk are required.