Treatment of Patients With Dual HCV and HBV Infection
Treatment of Patients With Dual HCV and HBV Infection
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.
Worldwide, the majority of hepatitis C patients have chronic hepatitis C virus (HCV) monoinfection. In areas or countries where hepatitis B virus (HBV) infection is endemic, such as Taiwan, it is not uncommon to encounter patients infected with both hepatitis viruses. In the past decade, the following issues regarding dual HCV/HBV infection were resolved. First, epidemiologic studies demonstrated that in patients with dual chronic hepatitis C and B, the disease manifestations are usually more severe than those with either virus infection. In support of these data, a large follow-up study on Taiwanese patients demonstrated the combined effect of HCV and HBV infection on the progression of chronic liver disease. Therefore, patients dually infected with hepatitis C and B should be followed more closely and require effective treatment. Second, recent studies supported that selection of priority virus to be treated in patients with dual chronic hepatitis C/B can be determined by the viral activity of either one. In dually infected patients with active hepatitis C, pegylated interferon (Peg-IFN) alfa plus ribavirin (RBV) was effective to achieve HCV RNA clearance, that is, sustained virological response (SVR). Post-treatment 5-year follow-up demonstrated that the durability of HCV SVR was maintained in 97%. Besides, using Peg-IFN-based therapy, hepatitis B surface antigen (HBsAg) seroclearance was also documented in 5.4% of dually infected patients per year. Third, in addition to the control of viral infection, a large retrospective population-based study well demonstrated that the use of Peg-IFN plus RBV combination therapy significantly reduced the risk of hepatocellular carcinoma (HCC) (hazard ratio [HR] 0.75), liver-related mortality (HR 0.45), and all-cause mortality (HR 0.39). All these data were presented and certain unresolved issues will be discussed in this mini-review.
Abstract and Introduction
Abstract
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.
Introduction
Worldwide, the majority of hepatitis C patients have chronic hepatitis C virus (HCV) monoinfection. In areas or countries where hepatitis B virus (HBV) infection is endemic, such as Taiwan, it is not uncommon to encounter patients infected with both hepatitis viruses. In the past decade, the following issues regarding dual HCV/HBV infection were resolved. First, epidemiologic studies demonstrated that in patients with dual chronic hepatitis C and B, the disease manifestations are usually more severe than those with either virus infection. In support of these data, a large follow-up study on Taiwanese patients demonstrated the combined effect of HCV and HBV infection on the progression of chronic liver disease. Therefore, patients dually infected with hepatitis C and B should be followed more closely and require effective treatment. Second, recent studies supported that selection of priority virus to be treated in patients with dual chronic hepatitis C/B can be determined by the viral activity of either one. In dually infected patients with active hepatitis C, pegylated interferon (Peg-IFN) alfa plus ribavirin (RBV) was effective to achieve HCV RNA clearance, that is, sustained virological response (SVR). Post-treatment 5-year follow-up demonstrated that the durability of HCV SVR was maintained in 97%. Besides, using Peg-IFN-based therapy, hepatitis B surface antigen (HBsAg) seroclearance was also documented in 5.4% of dually infected patients per year. Third, in addition to the control of viral infection, a large retrospective population-based study well demonstrated that the use of Peg-IFN plus RBV combination therapy significantly reduced the risk of hepatocellular carcinoma (HCC) (hazard ratio [HR] 0.75), liver-related mortality (HR 0.45), and all-cause mortality (HR 0.39). All these data were presented and certain unresolved issues will be discussed in this mini-review.