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

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.

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 I², τ² 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.

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.

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.