Systematic review with meta-analysis: combination treatment of regimens based on pegylated interferon for chronic hepatitis B focusing on hepatitis B surface antigen clearance

Background: The seroclearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) is considered to be associated with favourable clinical outcomes. Aims: This meta-analysis was performed to establish the proportion of HBsAg loss rates among CHB patients who received combination treatment based on pegylated interferon (PegIFN). Four combination strategies have been studied with the aim of improving HBsAg loss: de novo, NA-experienced, switch-to and add-on. This meta-analysis was performed to determine which, if any, of these combination strategies was more effective. Methods: Medline, Web of Science and Embase databases were searched from inception to December 2017. The proportion of patients who achieved HBsAg loss after combination therapy was pooled using a random-effects model. Results: Twenty-four studies fulfilled the meta-analysis criteria. The overall pooled proportion suggested that the rate of HBsAg loss could be increased to 9% (95% CI: 7%-12%) based on the combination treatment in CHB patients. Compared with de novo strategy (8%, 95% CI: 6%-10%), the nucleos(t)ide analogues-experienced (11%, 95% CI: 8%-15%) was found to be more likely (P=0.036) to achieve a response. Compared with the add-on strategy (8%, 95% CI: 5%-13%), the switch-to (14%, 95% CI: 9%-20%) was found to be more likely (P=0.012) to achieve HBsAg loss. Conclusion: The nucleos(t)ide analogues-experienced strategy was more effective than the De novo strategy in achieving HBsAg loss for CHB patients. Combination treatment using regimens based on Peg-IFN may be useful to help nucleos(t)ide analogues-treated patients, who have experienced at least 48 weeks of nucleot(s)ide analogue, achieve HBsAg seroclearance.