Glutathione S-transferase T1 mismatch is a risk factor for chronic ductopenic rejection of liver allografts.

The underlying causes of chronic rejection (CR) after liver transplantation are not completely known. The main aim of this study was to explore the involvement of the minor histocompatibility antigen glutathione S-transferase T1 (GSTT1) in CR. We retrospectively studied 611 patients who underwent liver transplants at University Hospital Virgen del Rocio between 2003 and 2016 with a median follow-up of 7.4±4.2 years. The GSTT1 genotype was determined by PCR. We defined GSTT1 mismatch as a specific donor/recipient combination in which a recipient who was homozygous for the deletion allele received a transplant from a positive donor. The prevalence of CR in our whole cohort was 11.6% (71/611), and the prevalence in the GSTT1-mismatched group was 18.8% (16/85) vs 10.5% (55/526) in the GSTT1-matched group. In the Cyclosporine A (CsA) group, the prevalence was 26.3% (26/99), much higher than the 8.8% (45/512) observed in the Tacrolimus (Tac) group. For statistical analysis, the patients were distributed into two groups: group 1, regarded as GSTT1-mismatched, which included the D+/R- allelic combination, and group 2, regarded as GSTT1-matched, which included the other allelic combinations (D+/R+, D-/R- and D-/R+). All relevant clinical information was collected, and diagnosis of CR was always confirmed by liver biopsy. GSTT1 mismatch (HR, 2; 95% CI, 1.1-3.7; P=0.03) and use of CsA/Tac (P<0.001) were independent risk factors for CR. CR increased the risk of mortality (HR, 2; 95% CI, 1.2-3.6; P=0.01). Twelve out of the 71 CR patients (16.9%) needed retransplantation. Conclusion: The GSTT1 D+/R- allelic mismatch is an independent risk factor for CR. A long follow-up of liver-transplanted patients is recommended, as the incidence of CR in adults seems to be underestimated.