Impact of hepatitis B surface antigen quantification on achieving a functional cure in patients with chronic...

Baseline hepatitis B surface antigen (HBsAg) levels are associated with the likelihood of achieving HBsAg loss which defines a functional cure. However, optimal HBsAg cut-offs for predicting HBsAg loss have not been systematically investigated. Therefore, in this systematic review and meta-analysis, we evaluated the impact of baseline levels of HBsAg on achieving a functional cure in patients with chronic hepatitis B (CHB).

We searched PubMed, Embase, and the Cochrane Library up to December 31, 2023, to identify studies comparing combination therapy with nucleos(t)ide analogues (NAs) and conventional/pegylated interferon (IFN) versus monotherapy. We pooled the proportions of HBsAg loss among studies stratified by different 75^th percentile of baseline HBsAg levels and other clinical characteristics.

We included 24 studies with 3446 participants. At the end of treatment, studies recruiting patients with 75^th percentile of baseline HBsAg below 500 and 1000 IU/mL had the highest proportions of HBsAg loss in the combination group, reaching 14 % (95 % CI: 9-21 %) and 17 % (95 % CI: 10-24 %), respectively. One-year IFN-NAs combination treatment achieved a higher proportion of HBsAg loss (9 %, 95 % CI: 6-12 %) than six-month IFN-NAs treatment (1 %, 95 % CI: 0-2 %). Patients with normal alanine transaminase (ALT) had higher HBsAg loss (11 %, 95 % CI: 6-17 %) than those with elevated ALT (4 %, 95 % CI: 2-7 %). Meta-regression indicated a positive association between male percentage in studies and HBsAg loss.

The optimal baseline HBsAg thresholds would be 500-1000 IU/mL, which represents high-response subpopulations for achieving a functional cure with currently available therapy.