OBJECTIVES: Published network meta-analyses (NMAs) of chronic hepatitis B (CHB) treatments are either out-of-date or excluded key treatments. Therefore, we aimed to comprehensively update the efficacy evidence for the following endpoints: Hepatitis B surface antigen (HBsAg) loss, Hepatitis B early Antigen (HBeAg) seroconversion and Hepatitis B virus deoxyribonucleic acid (HBV DNA) suppression.

METHODS: Approved treatments in CHB and their combinations were evaluated. A systematic literature review (SLR) was conducted to identify all randomized controlled trials (RCTs) in treatment-naïve CHB patients. Included studies reported at least one of the endpoints of interest. A frequential NMA was performed for each endpoint. The choice of fixed effect or random effect model was based on the I-square statistic, a measure of variation in study outcomes between studies. The analyses were performed separately for HBeAg-positive and HBeAg-negative patients. For the primary analyses, endpoints measured 48±4 weeks after treatment initiation were considered.

RESULTS: A total of 47 RCTs (13,826 patients), covering 23 unique treatment regimens, were included: 29 reported HBsAg loss, 36 reported HBeAg seroconversion and 37 reported HBV DNA suppression. For both HBsAg loss and HBeAg seroconversion, pegylated interferon-based regimens were the most effective strategy in both HBeAg positive and HBeAg negative patients. On the other hand, for HBV DNA suppression, nucleosides-based regimens were the most effective strategy in both HBeAg positive and HBeAg negative patients.

CONCLUSIONS: Our findings confirm available evidence around the comparative efficacy of available CHB treatments. Therefore, they can be used to update relevant cost-effectiveness analyses and clinical guidelines.