The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta‐analysis

Abstract

Current therapies for Chronic Hepatitis B (CHB) include nucleos(t)ide analogues (NA) and interferon (IFN) but their relative efficacy as monotherapy or in combination has not been examined systematically for HBsAg loss (functional cure). Hence we systematically reviewed the evidence for HBsAg loss in CHB patients treated with IFN, NA or the combination.We searched PubMed, EMBASE and abstracts from EASL, APASL and AASLD forrandomized controlled trials of CHB patients, comparing NA, IFN or the combination.The Cochrane Risk of Bias tool v2.0 and GRADE method were used. Analyses were stratified by NA genetic barrier, cirrhosis, type of combination therapy, HBeAg, treatment naivety, interferon dosage/duration and outcome duration. Sensitivity analysis was performed for selected strata and HBsAg loss was measured at the end‐of‐study(EOS), end‐of‐treatment(EOT) or end‐of‐followup(EOF). Effects were reported as risk differences (RD) with 95% confidence intervals (CI) using a random‐effects model. Forty five studies were included, all with low risk of bias. For HBsAg loss at EOS, when comparing combination versus IFN, RD=1%, 95%CI‐1%,2%; combination versus NA, RD=5%, 95%CI 3%,7%; IFN versus NA, RD=3%, 95%CI 2%,5%. Subgroup analysis showed a significant effect of standard IFN dose versus non‐standard; IFN duration≥48weeks versus 2years of followup. Similar findings were seen in HBsAgseroconversion but only 3 studies reported HBsAgseroreversion. In conclusion, IFN monotherapy/combination had a small but significant increase in HBsAg loss over NA, associated with standard dose of IFN and ≥48weeks of therapy, although this effect faded over time.