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

Summary Background The seroclearance of hepatitis B surface antigen ( HB sAg) 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 HB sAg loss rates among CHB patients who received combination treatment based on pegylated interferon (Peg IFN ). Four combination strategies have been studied with the aim of improving HB sAg 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 HB sAg 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 HB sAg 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 HB sAg loss. Conclusion The “nucleos(t)ide analogues‐experienced” strategy was more effective than the “De novo” strategy in achieving HB sAg 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 HB sAg seroclearance.