SAN FRANCISCO – Both donor and recipient interleukin 28B genotype affect the risk of recurrence of hepatitis C after liver transplantation, but they do so in opposite directions.
Investigators led by Dr. Andres Duarte-Rojo of the Mayo Clinic in Rochester, Minn., studied a cohort of more than 200 patients with hepatitis C who underwent liver transplantation, finding that 32% had a histologic recurrence 1 year later.
The risk of such recurrence was reduced by more than half when the recipient had the interleukin 28B (IL28B) CC genotype, as compared with the CT or TT genotype, according to results reported at the annual meeting of the American Association for the Study of Liver Diseases. In sharp contrast, the risk was almost tripled if the donor had the CC genotype for IL28B instead of one of the others.
"Variations in the phenotypic expression of IL28B genotype occur in relation to its source, either the recipient or the donor. This paradoxical effect suggests variation in the activation of the adaptive immune system according to hepatic and nonhepatic IL28B genotype," Dr. Duarte-Rojo commented.
Other research by his group suggests that donor and recipient CC genotype have a synergistic effect in promoting sustained virologic response after transplantation. "However, according to current results, allocation of a CC allograft to hepatitis C patients may predispose to a more severe disease in those untreated or not achieving a sustained virologic response," he said.
IL28 is a cytokine playing a role in antiviral defenses. The genotype for the B isoform "affects hepatitis C virus eradication, whether spontaneous or therapy driven," Dr. Duarte-Rojo noted. "It is important to study the associations of IL28B in the posttransplant setting to unravel mechanisms driving viral-host interactions and help the understanding of this polymorphism in hepatitis C pathobiology."
The investigators studied 241 consecutive patients with hepatitis C virus infection who underwent liver transplantation between 1995 and 2010. Average age was 52 years and the mean Model for End-Stage Liver Disease (MELD) score was 15.
IL28B genotype of recipient and donor was assessed from liver biopsies done at the time of transplantation, and serial biopsies of the liver graft were done after transplantation to assess virologic and histologic measures of recurrence.
Only 31% of the recipients had the IL28B CC genotype, compared with 52% of the donors, Dr. Duarte-Rojo reported.
The time to virologic recurrence after transplantation was longer when the recipient had the CC genotype vs. a non-CC genotype (4.6 vs. 4.1 months), whereas it was nonsignificantly shorter when the donor had the CC vs. a non-CC genotype.
Similarly, the proportion of patients that developed histologic recurrence as defined by stage 2 or greater fibrosis 1 year post transplantation was lower when the recipient had the CC vs. a non-CC genotype (19% vs. 38%). In contrast, recurrence rate was higher when the donor had the CC vs. a non-CC genotype (43% vs. 23%).
And there was also an interaction, whereby the proportion with recurrence ranged from a low of 17% with a CC recipient and non-CC donor, to a high of 52% with a non-CC recipient and a CC donor.
In a multivariate analysis that included factors such as alanine aminotransferase level, MELD score, viral genotype, surgical and biliary complications, cytomegalovirus infection, and diabetes, the risk of recurrence was still markedly decreased when the recipient had the CC genotype (odds ratio, 0.40) and markedly increased when the donor had the CC genotype (OR, 2.71).
The results were essentially the same after exclusion of patients who received antiviral therapy, according to Dr. Duarte-Rojo.
He noted that the recipient and donor IL28B genotypes also had opposite effects on alanine aminotransferase levels, viral loads, and rates of acute cellular rejection during follow-up.
Dr. Duarte-Rojo reported that he had no relevant conflicts of interest.