Hepatitis B Virus Reactivation Risk With <scp>IL</scp> ‐17, <scp>IL</scp> ‐23/ <scp>IL</scp> ‐12, or <scp>JAK</scp> Inhibitors: A Systematic Review and Meta‐Analysis

ABSTRACT Background and Aims This study aimed to determine the incidence of hepatitis B virus reactivation (HBVr) in patients with chronic or occult HBV infection who were treated with IL‐12/23, IL‐23 (together referred to as anti‐IL‐23/12), IL‐17, or JAK inhibitors without antiviral prophylaxis. In addition, we sought to assess whether the risk of HBVr varies according to anti‐HBs status among individuals who are anti‐HBc positive. Methods A systematic review and meta‐analysis were conducted in accordance with PRISMA and MOOSE guidelines (PROSPERO: CRD42024614179). Twenty‐nine studies including 912 patients were analysed. Incidence rates were pooled using a generalized linear mixed‐effects model (GLMM). Heterogeneity was assessed using I 2 , τ 2 and Cochran's Q . In a separate analysis, pooled odds ratios (ORs) were calculated using the random‐effects GLMM with a logit link to compare HBVr risk in anti‐HBc + patients with and without anti‐HBs antibodies. Results In HBsAg‐positive patients, HBVr incidence was highest with JAK inhibitors (40%; 95% CI: 16%–70%), followed by IL‐17 (28%; 95% CI: 14%–46%) and IL‐12/23 or IL‐23 inhibitors (10%; 95% CI: 3%–29%), with minimal heterogeneity. Among HBsAg‐negative/anti‐HBc + patients, HBVr risk remained low (1%–4%). Anti‐HBs negativity was associated with a statistically non‐significant increase in the risk of hepatitis B virus reactivation (OR 1.13, 95% CI 0.35–3.61), although the magnitude of this association was modest. Conclusion HBVr is a substantial risk in untreated HBsAg‐positive patients receiving JAK or IL‐17 inhibitors. Reactivation remains uncommon in anti‐HBc + individuals, particularly those with anti‐HBs. These findings support serostatus‐based risk stratification and the need for individualized antiviral prophylaxis.