Abstract and Introduction
Abstract
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.
Introduction
In areas where hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is endemic, a substantial number of patients are infected with both viruses. Those dually infected have been reported to face a significantly higher (two to threefold) risk of developing advanced liver disease and hepatocellular carcinoma (HCC) than those with either infection alone. Data from the REVEAL cohort recently confirmed this finding. Thus, they need to be treated more actively. In our previous trial, the sustained virological response (SVR) in patients with HCV genotype 1 infection 6 months following the completion of combination therapy with peginterferon (PegIFN) α-2a and ribavirin (RBV) was 72.2% in dually-infected patients versus 77.3% in mono-infected patients; for patients with HCV genotype 2–3 infections, the SVR values were 82.8% and 84.0% respectively. Post-treatment 5-year study further demonstrated that HCV SVR was maintained in ~97% of the patients who achieved SVR 6 months after the end of treatment. In addition, post-treatment HBsAg seroclearance was observed in 11.2% of 161 dually-infected patients. These results suggest that the combination therapy is as effective in clearing hepatitis viruses in patients with dual HCV–HBV infection as it is in patients with HCV mono-infection.
Previous studies have suggested that among patients with chronic hepatitis C (CHC) only, interferon/PegINF ± RBV therapy not only cured HCV infection in the short term but significantly decreased the risk of HCC and liver-related mortality. For example, during a mean follow-up of 5 years in a Taiwanese study, the cumulative incidence of HCC was 35.2% for 562 untreated patients and 12.2% for 1057 treated patients. However, it remains to be determined whether anti-HCV therapy can similarly decrease the risk of developing HCC and improve the overall survival among HCV–HBV dually-infected patients.
Since it is ethically impossible to conduct a randomised trial to learn the long-term efficacy of antiviral therapies, we can only rely upon the large database to explore the effect in reducing HCC. This study assembled a large population-based cohort with well documented nationwide clinical databases to examine whether anti-HCV therapy can improve the clinical outcomes of patients with dual HCV–HBV infection in comparison with untreated patients or with HCV mono-infected patients.