Source Medical Department III, University Hospital Aachen, Germany.

Fibrosis recurrence after liver transplantation (LT) for hepatitis C (HCV) is a universal event and strongly determines the patients' prognosis. Recipient risk factors for fibrosis recurrence are still poorly defined. We here assess a genetic risk score as a predictor of fibrosis post LT. The cirrhosis risk score (CRS), comprising allele variants in seven genes (AP3S2, AQP2, AZIN1, DEGS1, STXBP5L, TLR4 und TRPM5) was calculated in 137 patients who underwent LT for HCV infection and experienced HCV re-infection of the graft.

Patients were stratified into three categories according to a CRS score of <0.5, 0.5-0.7 or >0.7, respectively. All patients underwent protocol biopsies post LT (median follow-up 5 years) and liver fibrosis was assessed according to the Desmet Score. Data was analyzed by univariate and multivariate analyses. The results show that the highest CRS category was strongly associated with the presence of F2 or F3 fibrosis in protocol biopsies in years 1, 3 and 5 post LT (P=0.006, P=0.001 and P=0.024, respectively). Overall, 75.0% of patients with a CRS >0.7 developed at least F2 fibrosis, while 51.5% developed F3 fibrosis during follow-up. The predictive value of the CRS for fibrosis progression was independent of known clinical risk factors, including age of donor, gender of recipient and acute rejections. Kaplan-Meier analysis confirmed the prognostic value of the CRS with regards to recurrence of severe liver fibrosis in HCV infected patients post LT (log rank 6.23, P=0.032).

In conclusion, this genetic signature of the recipient predicts the likelihood of severe liver fibrosis in the graft after HCV recurrence. The CRS might help guiding early clinical decision making, e.g. the selection of patients for antiviral therapies, post LT.