March 26, 2021
Seeking to shorten wait time to transplant for patients with end-stage liver disease, Mayo Clinic transplant hepatologists and surgeons led a multisite, prospective observational study of liver transplant using allografts from donors with hepatitis C virus for recipients who are HCV-seronegative. Outcomes proved positive: direct-acting antiviral (DAA) therapy cleared HCV infection in nearly 100% of patients treated post-transplant, and the wait time was much shorter.
"Before, we had only case reports or single-center studies of this type of transplant," says Surakit Pungpapong, M.D., a transplant hepatologist at Mayo Clinic's campus in Florida. "This is one of the first two multicenter studies demonstrating its safety. Mayo Clinic now is among the first centers to conduct this type of transplant."
Transplanting HCV-infected organs to patients not infected with HCV is novel: Previously, only patients with HCV-positive livers received HCV-positive livers. Dr. Pungpapong, an author of the study published in the Journal of Hepatology in 2021, says recipients received transplants much more rapidly compared with regional and national transplant figures.
"This is very needed to expand the donor pool," he says. "The wait time is much shorter, on average, if a patient is willing to accept a hepatitis C liver. At Mayo Clinic's campus in Florida, for instance, we have a higher rate of offer acceptance for these livers and the other extended criteria livers, and patients have nearly two times the chance of getting a transplant compared with the national average. This means fewer patients are dying at our medical center while on the waitlist."
Study design and objectives
In this study, 34 patients with end-stage liver disease and a median Model for End-Stage Liver Disease (MELD) score of 20 received grafts from 20 donors who were HCV viremic and 14 donors who were HCV non-viremic between January 2018 and September 2019, including seven from donors who were cardiac-dead and six with simultaneous liver-kidney transplant. All patients started DAA therapy at a median of 27.5 days — as early as possible after transplant — and the investigators observed minimal adverse events and tolerable side effects. No viremia developed in patients who received non-viremic grafts; all of those who received HCV-viremic grafts received treatment and attained sustained virologic response status, indicating that HCV was successfully eradicated.
This study is part of an effort to reduce waitlist mortality by means of studying extended criteria organ transplant options. Mayo Clinic transplant hepatologists and surgeons are keen to expand the donor pool given observation of poor functional status in some patients with lower MELD scores, putting them at risk of mortality prior to reaching the top of the waitlist. This approach, along with transplanting livers from donation after cardiac death donors and other extended criteria donors, has shortened waitlist times overall at Mayo Clinic's campuses and increased transplant rates, providing opportunity for patients whose end-stage liver disease puts them at far greater risk of death than their MELD scores imply.
The concept of HCV-seropositive liver use for transplant in patients who are HCV seronegative
Recent advances in DAA therapy not only make feasible transplant of HCV-seropositive livers into patients who are HCV-seronegative, but they also mean that fewer patients on the transplant waiting list have HCV. Dr. Pungpapong calls DAA a success story of the past four to five years, eradicating infection in more than 95% in first line treatment. The small percentage failing first line treatment undergoes second line treatment, in which more than 95% clear the infection. "The function of the transplanted livers that are hepatitis C positive has been excellent, and we can treat the infection easily," says Dr. Pungpapong.
Another key benefit of DAA treatment for HCV and its success has been a decrease in organ discard due to few infected patients requiring transplant.
An advantage of using HCV-seropositive livers is that these donors frequently are young and have good-quality livers, despite the infection. Dr. Pungpapong says, however, that it's important to assess whether the donor's liver has developed any fibrosis, ideally with a biopsy.
Transplanting HCV-seropositive livers often isn't necessary for patients with high MELD scores and HCV-seronegative livers, as they will reach the top of the list and be transplanted. However, Dr. Pungpapong says numerous other patients are struck with disabling complications from liver disease, but their lower MELD scores don't reflect those issues. "We want these patients to accept HCV-seropositive livers because their MELD scores don't reflect how ill they are," says Dr. Pungpapong.
Patients must consent to receiving an HCV-seropositive liver. Patients who are HCV seronegative have been receptive to receiving these livers, however, says Dr. Pungpapong. "Many understand that HCV infection can be cured," he says. "Over the past three years, more and more patients are open to it. They've heard about it on the news or talked to other patients and learned it's been okay, and right now the acceptance rate of these livers has been much better than at the start."
Treatment costs
Antiviral treatment for HCV infection is still restrictive and expensive, and it requires insurance authorization once a patient who's undergone transplant with an HCV-seropositive liver has a confirmed viral load. Currently, only specialty pharmacies carry DAAs. Though when DAA treatment occurs remains dependent on payer authorization and appeal processes, target timing is within four to six weeks post-transplant to allow for these steps to take place without compromising outcomes; currently, only 1% experience severe fibrosing cholestatic hepatitis C.
Mayo Clinic not only transplants HCV-seropositive livers to patients who are HCV-seronegative but also now performs heart, lung and kidney transplants in similar circumstances. To date, according to Dr. Pungpapong, more than 150 patients have undergone solid organ transplants using allografts from donors who are HCV-seropositive at the three Mayo Clinic transplant centers with excellent post-transplant outcomes, and the number is growing rapidly.
For more information
Aqel B, et al. Outcomes following liver transplantation from HCV-seropositive donors to HCV-seronegative recipients. Journal of Hepatology. 2021;74:873.