Cirrhosis Risk Score of the Donor Organ Predicts Early Fibrosis Progression after Liver Transplantation
Anca Zimmermann1, Felix Darstein1,2, Maria Hoppe-Lotichius3, Gerrit Toenges4, Anja Lautem3, Frédéric Abel1, Arno Schad5, Jens Mittler2,3, Johanna Vollmar1, Daniel Grimm1, Hauke Lang2,3, Peter R. Galle1,2, Tim Zimmermann1,2 *, Detlef Schuppan6,7*
1) 1st Department of Medicine, Cirrhosis Center Mainz (CCM), University Medical Center Mainz, Germany
2) Interdisciplinary Transplant Center, University Medical Center Mainz, Germany
3) Department of General-, Visceral- and Transplantation- Surgery, University Medical Center Mainz, Germany
4) Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Mainz, Germany
5) Institute of Pathology, University Medical Center, Mainz, Germany
6) Institute of Translational Immunology, Liver Fibrosis Center, University Medical Center Mainz, Germany
7) Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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.
Key words: liver transplantation – fibrosis – cirrhosis risk score.
Abbreviations: CRS: cirrhosis risk score; D: donor; FP: fibrosis progression; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; HR: hazard ratio; LT: liver transplantation; N fib: number of patients with fibrosis ≥F2; R: recipient; RC: recurrent cirrhosis.