Objective Whether peginterferon α and ribavirin combination therapy reduces risk of hepatocellular carcinoma (HCC) or improves survival in patients dual-infected with hepatitis C virus (HCV) and hepatitis B virus (HBV) is unknown. Since it is ethically impossible to conduct a randomised trial to learn the long-term efficacy, we rely upon the large database to explore the effectiveness of combination therapy among dual-infected patients.

Design Data for this population-based retrospective cohort study were obtained from the treatment programme, Cancer Registry, National Health Insurance and death certification. We examined the risk of HCC, mortality and adverse events in 1096 treated and 18 988 untreated HCV–HBV dually-infected patients. Outcomes were analysed using the bias corrected inverse probability weighting (IPW) by propensity scores. Outcomes of HCV–HBV dually-infected and HCV mono-infected patients receiving the same treatment were compared using new user design with IPW estimators to adjust for confounding.

Results After adjustment, combination therapy significantly reduced the risk of HCC (HR 0.76, 95% CI 0.59 to 0.97), liver-related mortality (HR 0.47, 95% CI 0.37 to 0.6) and all-cause mortality (HR 0.42, 95% CI 0.34 to 0.52). Nevertheless, the underlying HBV infection was still a risk factor for HCC and mortality after treatment. Treatment was associated with an increase in the incidence of thyroid dysfunction (HR 1.9, p<0.001) and mood disorders (HR 1.81, p=0.005).

Conclusions This is the first evidence showing that combination therapy decreased the risk of HCC and improved survival in HCV–HBV dually-infected patients despite a slight increase in the incidence of thyroid and mood disorders.