JAK inhibitors are associated with higher hepatitis B virus reactivation rates than IL-12/23 or IL-17 inhibitorsSpecific Immune Inhibitors Show Varying Risks for Hepatitis B Reactivation

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, τ 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.