Incidence and risk factors for hepatitis B virus reactivation in kidney transplant recipients: a systematic review and meta-analysis.

backgroundKidney transplant recipients (KTRs) receiving immunosuppressive therapy are at risk for hepatitis B virus reactivation (HBVr), which can impair graft function; however, the incidence and risk factors for HBVr remain unclear, prompting this systematic review to evaluate these parameters in this population.

methodsFollowing PRISMA guidelines, we systematically searched PubMed, Embase, the Cochrane Library, Web of Science, CNKI, and Wanfang for studies published up to February 18, 2026. Studies reporting HBVr incidence in KTRs were included. A random-effects model was used to calculate pooled HBVr incidence with 95% confidence intervals (CIs). Subgroup analyses were performed based on publication year, sample size, country, antiviral prophylaxis, hepatitis B surface antibody status, different immunosuppressive regimens, and other variables. Meta-regression was conducted to explore sources of heterogeneity based on age, publication year, sample size, different immunosuppressive regimens, and other covariates. Pooled hazard ratios with 95% CIs were calculated for risk factors associated with HBVr. Methodological quality was assessed using the ROBINS-I tool. Sensitivity analysis was performed using the leave-one-out method. Publication bias was evaluated using funnel plots, trim-and-fill analysis, and Egger’s and Begg’s tests.

resultsA total of 32 studies were included in the meta-analysis. The pooled HBVr rate among KTRs was 9.34% (95% CI: 5.45–15.55%). In HBsAg(hepatitis B surface antigen)-positive KTRs (14 studies), the pooled HBVr rate was 37.96% (95% CI: 23.07–55.52%). Subgroup analysis revealed that studies published before 2010 reported a significantly higher HBVr rate than those published between 2021 and 2024 (59.59% [95% CI: 43.65–73.73%] vs. 26.15% [95% CI: 19.32–34.37%]; p < 0.001). Furthermore, patients who did not receive antiviral prophylaxis had a markedly higher HBVr rate compared to those who received prophylaxis (86.79% [95% CI: 74.79–93.57%] vs. 17.39% [95% CI: 7.86–34.20%]; p < 0.001). In HBsAg-negative/anti-hepatitis B core antigen (HBc)-positive KTRs (21 studies), the pooled HBVr rate was 4.2% (95% CI: 2.92–6.01%). Although HBsAb (Hepatitis B surface antibody)-negative patients showed a higher HBVr rate than HBsAb-positive patients, the difference was of borderline significance (9.34% [95% CI: 5.09–16.53%] vs. 2.30% [95% CI: 0.62–8.18%]; p = 0.05). In contrast, rituximab use was associated with a significantly higher HBVr rate compared to no use (5.92% [95% CI: 3.71–9.32%] vs. 1.52% [95% CI: 0.90–2.54%]; p < 0.001). Pooled analysis of risk factors identified two significant predictors of HBVr: rejection (HR 1.951, 95% CI: 1.108–3.435; p < 0.02) and negative anti-HBs status at transplantation (HR 10.444, 95% CI: 3.872–28.167; p < 0.001). Meta-regression revealed that publication year (β =−0.070, p = 0.016) and cyclosporin-based maintenance immunosuppression (β = 1.249, p = 0.015) were significant sources of heterogeneity in HBsAg-positive recipients. In HBsAg-negative/anti-HBc-positive recipients, study sample size (β =−0.004, p = 0.001) contributed to heterogeneity. No significant publication bias was detected among studies involving HBsAg-positive recipients. However, for HBsAg-negative/anti-HBc-positive recipients, although statistical tests showed no evidence of publication bias, funnel plot asymmetry suggested the potential absence of four studies with high HBVr rates, as indicated by trim-and-fill analysis.

conclusionsBased on the available data, HBVr appears to occur in a considerable proportion of KTRs. Among HBsAg-positive recipients, antiviral prophylaxis was associated with a lower HBVr rate. In HBsAg-negative/anti-HBc-positive recipients, pre-transplant anti-HBs-negative status and rituximab use were both associated with a higher reactivation rate. Post-transplant rejection and negative anti-HBs status at transplantation were also identified as potential risk factors for HBVr in this population. These findings may provide useful references for clinical monitoring and preventive strategies regarding HBVr in KTRs. CLINICAL TRIAL NUMBER: Not applicable.