Wednesday, May 23, 2012

IL28-Beta Genotype of Donor, Recipient Both Matter

May Newsletter

Elsevier Global Medical News

SAN FRANCISCO – Both donor and recipient interleukin-28-beta 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. At 1 year, 32% had a histologic recurrence of hepatitis C.

The risk of such recurrence was reduced by more than half when the recipient had the interleukin-28-beta (IL28-beta) 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 IL28-beta instead of one of the others.

“Variations in the phenotypic expression of IL28-beta 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 IL28-beta genotype,” Dr. Duarte-Rojo said.

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.

Interleukin-28-beta 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 IL28-beta in the osttransplant 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. Their average age was 52 years and the mean Model for End-Stage Liver Disease (MELD) score was 15.

The interleukin-28-beta genotype of the recipients and donors 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 interleukin-28-beta 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 months vs. 4.1
months), whereas it was not significantly shorter when the donor had the CC vs.a non-CC genotype.

Similarly, the proportion of patients that developed histologic recurrence of hepatitis C 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, the recurrence rate was higher when the donor had the CC genotype vs. a non-CC genotype (43% vs. 23%).
And there was also an interaction,whereby the proportion with hepatitis C 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 of the data that included factors such as alanine aminotransferase level, MELD score, viral genotype, surgical and biliary complications, cytomegalovirus infection, and diabetes, the risk of hepatitis C 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 interleukin-28-beta genotypes also had opposite effects on alanine aminotransferase levels, hepatitis C viral loads, and rates of acute cellular rejection during follow-up.

Dr. Duarte-Rojo reported that he had no relevant conflicts of interest.

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