As the evidence supporting the idea of transplanting livers infected with hepatitis C into patients who do not have the disease continues to mount, a multi-institutional team of researchers has developed a mathematical model that shows when hepatitis C–positive-to-negative transplant may improve survival for patients who might otherwise die awaiting a disease-free liver.
In a report published in the journal Hepatology (doi: 10.1002/hep.29723), the researchers noted how direct-acting antivirals (DAAs) have changed the calculus of hepatitis C (HCV) status in liver transplant by reducing the number of HCV-positive patients on the wait list and providing treatment for HCV-negative patients who receive HCV-positive livers. “It is important that further research in this area continues, as we expect that the supply of HCV-positive organs may continue to increase in light of the growing opioid epidemic,” said lead author Jagpreet Chhatwal, PhD, of Massachusetts General Hospital Institute for Technology Assessment in Boston.
Dr. Chhatwal and coauthors claimed their study provides some of the first empirical data for transplanting livers from patients with HCV into patients who do not have the disease.
The researchers performed their analysis using a Markov-based mathematical model known as Simulation of Liver Transplant Candidates (SIM-LT). The model had been validated in previous studies that Dr. Chhatwal and some coauthors had published (Hepatology. 2017;65:777-88; Clin Gastroenterol Hepatol 2018;16:115-22). Dr. Chhatwal and coauthors revised the SIM-LT model to simulate a virtual trial of HCV-negative patients on the liver transplant waiting list to compare outcomes in patients willing to accept any liver to those willing to accept only HCV-negative livers.
The patients willing to receive HCV-positive livers were given 12 weeks of DAA therapy preemptively and had a higher risk of graft failure. The model incorporated data from published studies using the United Network for Organ Sharing (UNOS) and used reported outcomes of the Organ Procurement and Transplantation Network to validate the findings.
The study showed that the clinical benefits of an HCV-negative patient receiving an HCV-positive liver depend on the patient’s Model for End-Stage Liver Disease (MELD) score. Using the measured change in life-years, the researchers found that patients with a MELD score below 20 actually witnessed reduction in life-years when accepting any liver, but that the benefits of accepting any liver started to accrue at MELD score 20. The benefit topped out at MELD 28, with 0.172 life years gained, but even sustained at 0.06 life years gained at MELD 40.
The effectiveness of using HCV-positive livers may also depend on region. UNOS Region 1 – essentially New England minus western Vermont – has the highest rate of HCV-positive organs, and a patient there with MELD 28 would gain 0.36 life-years by accepting any liver regardless of HCV status. However, Region 7 – the Dakotas and upper Midwest plus Illinois – has the lowest HCV-positive organ rate, and a MELD 28 patient there would gain only 0.1 life-year accepting any liver.
“Transplanting HCV-positive livers into HCV-negative patients receiving preemptive DAA therapy could be a viable option for improving patient survival on the LT waiting list, especially in UNOS regions with high HCV-positive donor organ rates,” said Dr. Chhatwal and coauthors. They concluded that their analysis could help direct future clinical trials evaluating the effectiveness of DAA therapy in liver transplant by recognizing patients who could benefit most from accepting HCV-positive donor organs.
The study authors reported having no financial disclosures. The study was supported by grants from the American Cancer Society, Health Resources and Services Administration, National Institutes of Health, National Science Foundation, and Massachusetts General Hospital Research Scholars Program. Coauthor Fasiha Kanwal, MD, received support from the Veterans Administration Health Services, Research & Development Center for Innovations in Quality, Effectiveness and Safety and Public Health Service.
SOURCE: Chhatwal J et al. Hepatology. doi:10.1002/hep.29723.