University of Arkansas for Medical Sciences, Division of Gastroenterology and Hepatology, Little Rock, AR, USA; Mayo Clinic, Division of Gastroenterology and Hepatology, Rochester, MN, USA.
The discovery of the IL28B single-nucleotide polymorphisms (SNPs) has opened an important new area of research in liver transplantation (LT) for hepatitis C (HCV). Both recipient and donor derived IL28B genotypes affect post-LT treatment response, with sustained virological response (SVR) rates oscillating between >50% in homozygotes for the favorable allele (up to 90% when this is present in both recipient and donor), to <15% SVR in homozygotes for the unfavorable allele, and 30-50% in the heterozygotes. Other key posttransplant outcomes affected by IL28B genotype are time to histological recurrence, HCV RNA and ALT levels, histological variables including the rate of fibrosis progression, and hepatocarcinoma. Interactions between donor and recipient IL28B genotype are complex and may affect outcomes not directly related to HCV infection, such as acute cellular rejection and metabolic diseases. A preferential allocation system, in which livers from donors who are homozygous for the favorable allele are given to HCV patients, might be postulated to improve SVR and post-LT outcomes in recipients with HCV infection (25% increase in SVR and 8% decrease in mortality at 5 years). Although difficult to predict, negative effects from this could include an accelerated progression of fibrosis in patients with failed HCV eradication, and an increase in acute cellular rejection in non-HCV patients. The precise role of IL28B genotypes in the course of post-LT HCV is evolving, but existing knowledge suggests the possibility of exploring strategies that use IL28B genotyping to reduce the impact of post-LT adverse outcomes.