Management Strategies and Clinical Outcomes in Steroid-resistant Rejection after Liver Transplantation: A Systematic Review and Meta-analysis.

OBJECTIVES

To synthesize the available evidence on management strategies and associated clinical outcomes of steroid-resistant rejection (SRR) following liver transplantation.

DESIGN

Systematic review and meta-analysis.

SETTING

Studies conducted in liver transplant centers worldwide published between 1987 and 2022.

PARTICIPANTS

Thirteen observational studies including 4378 liver transplant recipients, of whom 266 developed SRR.

DATA EXTRACTION AND SYNTHESIS: PROSPERO: CRD42024502525. A systematic search of major electronic databases was conducted through 30th September 2025, without language restrictions. Study selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Risk of bias was assessed using the ROBINS-I tool.

RESULTS

Thirteen observational studies published between 1987 and 2022 were included. The pooled incidence of SRR among liver transplant recipients was 6.7% (95% confidence interval [CI], 4.3-9.1), with substantial heterogeneity (I2 = 93.8%). SRR occurred early after transplantation, with a pooled mean time to onset of 61.6 days, with substantial heterogeneity (I2 = 74.8%). Initial management consisted of high-dose corticosteroid therapy. Second-line agents included anti-thymocyte globulin, muromonab-CD3, tacrolimus-based rescue or conversion, and interleukin-2 receptor antagonists; deoxyspergualin and bortezomib were used less frequently as salvage therapy. Overall, medical rescue therapy avoided retransplantation in 69.9% of patients. Pooled comparative risk ratios for individual rescue therapies could not be estimated, owing to heterogeneous study designs, sequential use of rescue agents within the same patient, and inconsistent outcome reporting.

CONCLUSIONS

SRR remains an uncommon but clinically significant complication after liver transplantation. Several rescue therapies have been used for SRR, but current evidence does not permit conclusions about their comparative effectiveness. This reflects substantial heterogeneity across studies and the absence of comparative trial data. Standardized management strategies and prospective multicenter studies are needed to guide clinical practice.