Z Gastroenterol 2011; 49 - V3_01
DOI: 10.1055/s-0030-1269653

A seven gene signature (cirrhosis risk score) predicts recurrence of severe liver fibrosis after liver transplantation for hepatitis C infection

NT Cabral do Ó 1, D Eurich 2, P Schmitz 1, M Schmeding 3, M Bahra 4, P Neuhaus 5, C Trautwein 1, UP Neumann 3, HE Wasmuth 1
  • 1Medizinische Klinik III Universitätsklinikum Aachen, Aachen
  • 2Department of General, Visceral, and Transplantation Surgery, Charité-Campus Virchow, Universitatsmedizin Berlin, Berlin
  • 3Chirurgische Klinik, Aachen
  • 4Charité Universitätsmedizin in Berlin; Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Berlin
  • 5Allgemein-, Viszeral- und Transplantationschirurgie, Experimentelle Chirurgie und Regenerative Medizin, Charité Universitätsmedizin Berlin, Berlin

Aims: Fibrosis recurrence after liver transplantation (LT) for hepatitis C (HCV) infection is a common event and a major determinant of the patients’ prognosis. The risk factors responsible for fibrosis progression post-LT are not well defined. We here assess whether a genetic risk score which predicts the progression of HCV induced fibrosis pre-LT is also associated with the development of severe fibrosis post-LT. Methods: Overall, the genetic cirrhosis risk score (CRS), comprising allele variants in seven genes (AP3S2, AQP2, AZIN1, DEGS1, STXBP5L, TLR4, TRPM5), was calculated in 138 patients who underwent LT for HCV infection. In all patients protocol biopsies were performed one, three and five years after LT and liver fibrosis was assessed by the Desmet and Scheuer score. Data was analyzed by univariate and multivariate analyses. Results: When applying the CRS of non-transplanted subjects, 46.7% of the transplanted patients had a CRS in the highest risk category (CRS category 3), while 26.3% were in category 2 (intermediate risk) and 27% in category 1 (low risk). Patients with a CRS category 3 were more likely to have at least stage 2 liver fibrosis in the protocol biopsies at year one (OR 4.0, P=0.01), year three (OR 3.8, P=0.002) and year five (OR 2.7, P=0.01) compared to subjects with CRS categories 1 and 2. The significant association of the CRS with progressive liver fibrosis in the graft at each protocol biopsy was independent of donor age, gender of recipient and BMI of recipient by multiple regression analysis (P=0.02 at year one, P=0.007 at year three and P=0.001 at year 5, respectively). Conclusions: A genetic signature of the recipient predicts the likelihood of progressive liver fibrosis in the graft after HCV recurrence. As progressive liver fibrosis of the graft significantly affects the prognosis of transplanted patients, the CRS might guide early clinical decision making, e.g. the selection of patients for antiviral therapies post-LT.

Cirrhosis risk score - Liver transplantation - fibrosis recurrence - hepatitis C virus infection