Preemptive DAA therapy viable for HCV-positive liver transplantation

Results of a virtual trial showed that transplantation with hepatitis C-positive livers with preemptive direct-active antiviral therapy may be a viable option for improving patient survival on the liver transplant waitlist, according to an expert at The Liver Meeting 2017.

“The fact is that donor liver availability continues to be limiting factor in increasing the number of liver transplants. Therefore, it becomes very important that we utilize all organs for a maximum potential,” Jagpreet Chhatwal, PhD, from the Massachusetts General Hospital and Harvard Medical School, said in his presentation. “However, under current guidelines, hep C-positive livers are not transplanted into hep C-negative recipients because of adverse post-transplant outcomes previously demonstrated in the interferon-based therapy [era]. But several things have changed in the last few years that prompt us to revisit this question. In particular, the availability of hep C-positive liver donors has increased substantially because of the ongoing opioid epidemic.”

In comment to Healio Gastroenterology and Liver Disease, Chhatwal added: “By accepting HCV-positive livers, patients time to transplant can be reduced, but it comes with the risk of not clearing the hep C infection after the transplant. New antivirals have approximately 95% efficacy in post-transplant setting. The study’s objective was to evaluate if and in which hep C-negative patients the benefits of accepting hep C-positive livers outweigh the risk associated with hep C infection.”

The researchers designed a simulated virtual trial to compare long-term outcomes of patients without HCV on the liver transplant waitlist who were willing to receive an HCV-positive liver with those only willing to accept HCV-negative livers.

The trial model included data from published studies and the United Network for Organ Sharing. Model patients who received HCV-positive livers were treated preemptively with 12 weeks of DAA therapy.

“Efficacy of preemptive treatment was based on data in hep C-positive recipients because we do not know any well-connected studies that show outcomes in hep C-negative recipients,” Chhatwal said. “I should emphasize that our study is not based on any specific drug regimen, it’s only based on the [sustained virologic response] rate that matters in being offered the transplant.”

Patients who were willing to accept livers that were either positive or negative for HCV had an increased life expectancy when their MELD score was at 20 or higher (range, 18-20, depending on UNOS region), compared with those who would only accept an HCV-negative liver.

The clinical benefit was greatest in UNOS regions with the highest HCV-positive liver donor rates. According to Chhatwal, the model outcomes had robust results based on sensitivity analysis with a wide range of parameters.

“Clinical trials are needed to confirm the efficacy of the results in this setting,” Chhatwal concluded. “In fact, our analysis can help inform future trials and minimize patient harm.” – by Talitha Bennett

Reference:

Chhatwal J, et al. Abstract 3. Presented at: The Liver Meeting; Oct. 20-24, 2017; Washington, D.C.

Disclosure: Chhatwal reports he is a consultant for Merck, Gilead, Complete HEOR Solutions and has received grants or research support from the National Institutes of Health National Center for Advancing Translational Sciences and the American Cancer Society.