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

ABSTRACT 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; I 2 = 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.