Background & Aims: Fibrosis progression (FP) after liver transplantation (LT) increases morbidity and mortality. Biomarkers are needed for early prediction of FP. A recipient’s seven-gene cirrhosis risk score (CRS) has been associated with FP, especially in non-transplant cohorts. A broader validation of CRS, including the genotype of the donor-organ and HCV-negative patients is lacking. We therefore analyzed the impact of donor- and recipient-specific genotypes on FP after LT in a large cohort of HCV-positive and -negative patients.Method: Genotyping from liver biopsies (n=201 donors) and peripheral blood (n=442 recipients) was performed. Cirrhosis risk score was correlated with FP at 1 and 5 years after LT.Results: Fibrosis ≥F2 was documented in 26.5% of the recipients’ CRS group (R-CRS) (defined by recipient’s genotype) and in 23.4% of the donors’ CRS- group (D-CRS) (defined by donor’s genotype). Cumulative incidence for fibrosis ≥F2 was higher in patients with D-CRS >0.7 (p=0.03). While the R-CRS showed no prognostic relevance, D-CRS >0.7 was associated with higher hazard ratios (HRs) for fibrosis ≥F2 (HR=2.04; p=0.01), especially in HCV-negative patients (HR=2.59, p=0.03). Donors’ CRS >0.7 was associated with higher risk for ≥F2 in 1-year protocol biopsies (p<0.001). Among the patients in whom both the recipient’s and donor’s CRS were available, fibrosis ≥F2 was encountered more frequently in patients with a D-CRS >0.7, in combination with any R-CRS, compared to patients with D-CRS scores ≤0.7 (p=0.034). Donors’ AZIN1, STXBP5L, TRPM5 genotypes carried a higher risk for fibrosis ≥F2 in subgroups.Conclusion: High D-CRS >0.7 predicted early FP after LT, especially in HCV negative patients.
The recipient CYP2D6 allele 4-associated poor metabolizer status correlates with an early fibrosis development after liver transplantation