IL28B CC or CT genotype have better liver graft survival in Hepatitis C

By Nancy Lapid

PHILADELPHIA (Reuters Health) May 03 - Researchers are a step closer to knowing which hepatitis C patients are more likely to lose their grafts after liver transplantation.

According to study results announced yesterday at the American Transplant Congress in Philadelphia, hepatitis C patients with the IL28B CC or CT genotype have better graft survival and longer times to histological recurrence than recipients with the TT genotype.

Hepatitis C viremia inevitably recurs after liver transplantation, leading to high rates of cirrhosis and graft loss. The new findings could mean that directing lower-risk organs (e.g., from younger donors, or with shorter cold ischemia times) to higher-risk recipients might improve their outcomes.

"This is clearly something that could have clinical implications," senior investigator Dr. Barbara Murphy from Mount Sinai Medical Center in New York City told Reuters Health. "There's already a lab-based assay available, so we could genotype the recipients. Certain labs have this up and going."

But Dr. Murphy won't say transplant programs should act now on these results. Her study, while large, was retrospective. "If you're going to change organ allocation -- if you're going to give one group preference for better organs -- you'd better have data" from randomized trials, she said.

Studies in hepatitis C patients who still have their native liver had already pointed to an impact from the IL28B gene, Dr. Murphy said. Individuals with the favorable polymorphism are more likely to have spontaneous clearance or a sustained virologic response to interferon-based therapy.
In a plenary session talk yesterday, her colleague Dr. Sridhar R. Allam reported on a study of 620 adult liver recipients for whom DNA samples were available for genotyping of IL28B (rs12979860); the cohort included 327 hepatitis C virus HCV-positive patients.

The research team also had genotype data for a subgroup of 377 consecutive donor DNA samples, and IL28B gene expression data from RNA isolated from pre-implantation liver biopsies of 33 donors.
Dr. Allam reported significantly better five-year graft survival with the IL28B CC or CT genotype vs. the TT genotype (61.8% vs. 47.9%, p=0.02) in patients with HCV infection. In the non-HCV control group, however, there was no difference in graft survival based on IL28B genotype.
Also, he said, recipients with C allele had delayed mean time to histological HCV recurrence after LT (25 vs. 15 months, p=0.02).

There was no association of donor IL28B genotype with graft survival, and no effect of IL28B genotype on IL28 RNA expression.

IL28 is known to affect innate immunity, but it's not clear why it impacts graft survival, Dr. Allam said.
When researchers do design randomized trials, among the most important things they'll want to see is whether any interventions -- such as shifting better-quality livers to patients at higher risk for graft loss -- will actually change outcomes, Dr. Murphy said.

Also, it will likely be important to consider IL28B genotype in trials of new protease inhibitors for HCV. "You would think the polymorphism would point to outcome," Dr. Murphy said. "They'll need to look for this in trial populations, to make sure it's not skewing the data."