1 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. 2 Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. 3 Duke Clinical Research Institute, Duke University Medical Center, Durham, NC. 4 Division of Transplantation Surgery, Mayo Clinic, Rochester, MN. 5 Epidemiology Unit, Division of Gastroenterology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.
BACKGROUND AND AIMS:
The IL28B genotype has been linked to sustained virological response (SVR) in hepatitis C virus (HCV). Its role on disease biology and progression is less clear. We characterized the effects of IL28B genotype on HCV recurrence, allograft histology, rate of SVR, and survival after liver transplantation (LT) in HCV.
Consecutive patients who underwent LT with HCV were studied. The rs12979860 genotype from both the donor was and recipient was determined. Measured endpoints included histologic HCV recurrence (inflammatory grade and fibrosis stage), acute cellular rejection, SVR, retransplantation, and death.
The study cohort comprised 272 consecutive LT in 255 patients. C-allele frequency was 56% in recipients and 70% in donors (P<0.001). Recipient IL28B CC genotype was associated with lower alanine aminotransferase levels and viral load at recurrence and a lower frequency of F≥2 on liver biopsy at 1 year after LT, when compared with the non-CC genotype (P=0.012). The opposite was observed in LT with donor CC genotype (P=0.003). Both recipient and donor CC genotype favored SVR, and when the two of them occurred together, the SVR rate reached 90%. Survival analysis after 5.5 years of follow-up showed a higher rate of progression to cirrhosis (hazard ratio, 5.96; 95% confidence interval, 1.29-27.6), liver-related death, or retransplantation among liver transplant recipients with a CC genotype donor.
The IL28B genotype is predictive not only of SVR but also of the histologic diagnosis of posttransplant hepatitis C, with donor CC genotype favoring inflammation and fibrosis, and adverse outcomes during long-term follow-up. A favorable effect of donor CC genotype is manifest only after antiviral therapy.