Cirrhosis risk score of the donor organ predicts early fibrosis progression after liver transplantation.

Background & Aims: Fibrosis progression (FP) after liver transplantation (Cl") 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' AZIN I , 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.