Research in context
Evidence before this study
We searched PubMed, Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and Web of Science using the following search algorithm: (((hepatitis B virus AND hepatitis C virus) OR HBV AND HCV OR (hepatitis B virus and C virus) OR (HBV/HCV)) AND ((coinfect* OR co-infect* OR dual infect* OR dual* infect*)) OR ((hepatitis B OR HBV OR hepatitis B virus) AND (hepatitis C OR HCV OR hepatitis C virus))) AND (react* OR direct acting OR DAA). The first publication on sofosbuvir (the first direct-acting antiviral [DAA] that was used in interferon-free regimens) was in October, 2010. We therefore searched for studies published between Oct 1, 2010, and Sept 30, 2017. All studies of patients with chronic hepatitis C virus (HCV) infection treated with interferon-free DAA regimens and reported to have active (hepatitis B surface antigen [HBsAg]-positive) or resolved (HBsAg-negative but hepatitis B core antibody [HBcAb]-positive) hepatitis B virus (HBV) infection at baseline were eligible for inclusion. All study types were eligible for inclusion. Conference proceedings, abstract books, and references from relevant reviews and original research articles were also examined for other potential studies. We found only one meta-analysis evaluating the risk of HBV reactivation in patients treated for HCV infection. However, the meta-analysis focused on HBV reactivation in patients with HBV and HCV coinfection receiving interferon-based treatments, and only two interferon-free studies comprising 18 HBsAg-positive patients were included. To our knowledge, no systematic review or meta-analysis exists evaluating the risk of HBV reactivation in patients with resolved HBV infection.
Added value of this study
Our study is, to the best of our knowledge, the first comprehensive meta-analysis of studies assessing the risk of HBV reactivation in patients with HCV infection treated with DAAs. Our findings suggest that, in patients with chronic HBV and HCV coinfection receiving DAA therapy, the risk of HBV reactivation is greater than that previously reported for patients treated with interferon, especially in patients with quantifiable (≥20 IU/mL) HBV DNA at baseline. The risk of HBV reactivation in patients with resolved HBV infection is low and no major clinical events were reported in this group.
Implications of all the available evidence
The risk of HBV reactivation in patients with HBV and HCV coinfection is similar to that seen in patients undergoing immunosuppression, in whom antiviral prophylaxis is recommended. The risk of HBV reactivation in patients with resolved HBV infection is low. Thus, our results support the use of antiviral prophylaxis in patients with chronic HBV infection, particularly in those with quantifiable HBV DNA, and repeated alanine aminotransferase and/or HBV DNA monitoring in those with resolved HBV infection.