Treatment of patients with dual hepatitis C virus and hepatitis B virus infection: resolved and unresolved issues

Dual hepatitis C virus (HCV)/hepatitis B virus (HBV) infection is not uncommon in HCV or HBV endemic areas and among subjects at risk of parenteral transmission. In patients dually infected with hepatitis C and B, the disease manifestations are usually more severe than those with either virus infection. In the past decade, the following issues have been resolved. In dually infected patients with active hepatitis C, combined pegylated interferon alfa plus ribavirin was effective, the treatment outcomes being similar to patients with HCV monoinfection. During long-term follow-up, the HCV response was sustained in around 97% of patients; and the long-term outcomes including the development of hepatocellular carcinoma and liver-related mortality were improved. However, several clinical issues remain to be resolved. First, host and viral factors influencing the long-term outcomes and treatment options in patients with dual HCV/HBV infection await further studies. Second, about 60% of dually infected patients with baseline undetectable serum HBV DNA levels develop HBV reactivation after the start of treatment. How to prevent and treat HBV reactivation should be clarified. Third, about 30% of dually infected patients lose hepatitis B surface antigen at 5 years after the end of combination therapy; the mechanisms need further investigations. Fourth, the optimal treatment strategies for dually infected patients with active hepatitis B or established cirrhosis should be explored in future clinical trials. Finally, the role of new direct-acting antiviral-based therapy for the treatment of patients with dual HCV/HBV infection also remains to be evaluated.