A systematic review and meta-analysis on gilbert syndrome and liver transplantation: safety of donor grafts and risk of post-transplant donor-derived gilbert syndrome

Abstract

• Gilbert syndrome is identified in about 4% of liver transplant donors. • Post-transplant Gilbert syndrome occurs in approximately 2% of recipients. • Donor grafts with Gilbert syndrome do not increase donor or recipient risk. • Donor-derived Gilbert syndrome occurs in 50% of cases and causes benign unconjugated hyperbilirubinemia. • Gilbert syndrome donor grafts can safely expand the liver donor pool. Gilbert syndrome (GS) is a benign hereditary disorder of bilirubin metabolism that may raise concerns regarding liver graft suitability and post-transplant hyperbilirubinemia. We conducted a systematic review and meta-analysis to evaluate the safety of liver transplantation (LT) using grafts from donors with GS and to determine the incidence and clinical relevance of donor-derived GS after LT. A systematic search identified controlled studies, single-arm cohorts, case series, and case reports evaluating LT from donors with GS or post-transplant development of GS. Controlled studies were synthesized using random-effects meta-analysis, while case-based evidence was analyzed using individual patient data (IPD) meta-analysis. Outcomes included donor and recipient complications, postoperative liver biochemistry, survival, and prevalence of GS among donors and recipients. Twenty-four studies (28 publications) comprising 424 donors and 419 recipients were included. Among 4,688 LT donors, the pooled prevalence of GS was 4.0% (95% CI, 2–8%; I² = 94%). Among 812 LT recipients, the pooled prevalence of post-transplant GS was 2.3% (95% CI, 1.2–3.5%; I² = 94%). In recipients transplanted with grafts from known GS donors (n = 32), the pooled prevalence of donor-derived GS was 50% (95% CI, 15–85%; I² = 66%). Meta-analysis of controlled studies showed no significant differences between GS and non-GS donors in donor complication rates (RR, 1.10; 95% CI, 0.77–1.33), length of hospital stay (MD, 12 days; 95% CI, −15 to 39), or one-year recipient survival (RR, 1.05; 95% CI, 0.96–1.14). GS donors exhibited a higher postoperative peak total bilirubin (MD, 1.65 mg/dL; 95% CI, 0.22–3.08), with no differences in peak alanine aminotransferase levels. IPD analysis of 61 published cases demonstrated excellent donor and recipient outcomes. Post-transplant GS manifested as isolated unconjugated hyperbilirubinemia in 29.5% of recipients, without associated graft dysfunction. Overall postoperative complications were uncommon (4.8%), and GS was not implicated in graft failure or mortality. Liver transplantation using grafts from donors with GS is safe and not associated with increased donor or recipient morbidity or mortality. Donor-derived or post-transplant GS represents a benign biochemical phenotype without adverse clinical consequences. These findings support the broader utilization of GS donor grafts to expand the liver donor pool.