Finite Versus Indefinite Nucleos(t)ide Analogue Therapy in HBeAg‑Negative Chronic Hepatitis B: Meta‑Analysis of...

Continuous nucleos(t)ide analogue (NA) therapy for chronic hepatitis B (CHB) effectively maintains viral suppression but rarely results in functional cure. Finite NA therapy has been proposed to increase rates of HBsAg loss; however, international guidelines provide conflicting recommendations. This study compares the efficacy and safety of finite versus continuous NA therapy in HBeAg-negative adults using randomized controlled trials. We included parallel-group randomized controlled trials (RCTs) comparing nucleos(t)ide analogue (NA) cessation versus continuation in non-cirrhotic, virally suppressed HBeAg-negative adults. Two reviewers independently screened studies and assessed risk of bias using Cochrane RoB 2. Random-effects Mantel-Haenszel meta-analyses with Hartung-Knapp adjustment and Paule-Mandel estimation were used to pool risk ratios (RRs) with 95% confidence intervals (CIs). Certainty of evidence was assessed using the GRADE approach. Four RCTs (n = 357) met inclusion criteria. Discontinuation increased HBsAg loss vs. continuation (RR 5.02, 95% CI: 0.47-53.47; I² = 21.8%; low certainty), corresponding to ~53 additional losses per 1000 patients. However, finite therapy markedly increased virologic relapse (RR 23.09) and retreatment (RR 21.94) while reducing sustained off-therapy virologic response (RR 0.46). Post-cessation ALT flares were frequent but self-limited or resolved with retreatment. No hepatic decompensation or serious adverse events occurred. In monitored, non-cirrhotic adults, finite NA therapy may increase the probability of HBsAg loss despite predictable relapse and retreatment. With no evidence of severe harm, these findings support finite therapy as a selective, patient-centered strategy toward functional cure in expert centers.