The use of HCV positive donors among non-HCV infected liver transplant recipients

In 2013, the United States Public Health Service proposed updated guidelines for reducing the transfer of human immunodeficiency virus, hepatitis B virus, and HCV virus through organ transplantation. [6] Application of these guidelines, along with the use of welltolerated, pan-genotypic direct antiviral drugs (DAA’s) could provide a controlled environment in which HCV-infected donor livers could be safely used in HCV-negative recipients. As for the credibility of the direct-acting antiviral drugs (DAA’s), they are proven to be effective in eliminating HCV infection from more than 95% of the allografts. [7] The sustained virologic response is said to occur when HCV RNA is no longer detectable after 12 weeks of DAA therapy and this corresponds with a decreased liver morbidity and mortality. [8,9] The timing for commencement of post-transplant DAA’s should ideally be as soon as possible to prevent graft complications, like fibrosing cholestatic hepatitis. [10] The type and duration of DAA therapy after LT depend on the genotype of the virus received from the donor. [11] HCV positive donors to HCV positive recipient LT using DAAs is a common practice and has led to a spike in the use of similar donors for uninfected recipients as well. A study conducted in 2021 showed a 35-fold increase in LT of HCV positive donors to HCV negative recipients in the last 4 years in the United States, increasing from 8 in 2016 to 280 in 2019. [12] Another study showed how DAA resulted in a threefold increase in LT from HCV positive to HCV negative recipients from 2015 to 2016. [13] This trend is supported by numerous studies with favorable outcomes for this strategy. A study carried out in 2018 at Stanford showed acceptable short-term outcomes for using HCV-positive donor grafts in 10 non-infected recipients. [14] All 10 non-infected recipients in the study received post-transplant donor HCV infection and each successfully achieved sustained virologic response after 12 weeks of direct antiviral drug therapy. [14] No graft loss or deaths were reported during a 380-day post-transplant follow-up period and as a result, the study emphasized the use of HCV-positive donor grafts to expand the LT donor pool. [14] A retrospective study conducted at Johns Hopkins Hospital examined 26 HCV seronegative patients who had received liver grafts from HCV seropositive donors between January 1, 2017, to August 31, 2019, resulted in good short-term outcomes for HCV cure following DAA’s. [11] In 2021, Cotter et.al reported no discernible impact on medium-term outcomes and excellent grafts survivals from HCV-infected donor to uninfected recipient LT. The 1-year graft survival rates were 91% and 90%and 2-year rates were 88.5% and 87% for HCV infected donor to HCV negative recipient and uninfected donor to uninfected recipient, respectively (p=0.672). [12] In another study, a single-centre retrospective analysis of LT performed on HCV seronegative recipients from HCV seropositive organs showed equal post-transplant complication rates between NAT-positive and NAT-negative recipients. [15] The study concluded that HCV seropositive organs could be safely used in HCV Liver transplantation (LT) is a life-saving procedure and in some cases, the only mode of management. It is an ideal form of treatment in conditions like end-stage liver disease, acute liver failure and hepatocellular carcinoma within specific criteria. Unfortunately, the liver transplant demand continues to exceed donor liver supply, this alarming disparity has resulted in a high waiting-list death rate. In a 2019 study (Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients, OPTN/SRTR), 52.2% of adult patients had to wait for more than 1 year for a liver transplantation. [1] A simultaneous increase in opioid-related deaths in the United States has left the organ procurement system with the increasing availability of young, hepatitis C virus (HCV) nucleic acid testing (NAT) positive donors, and they are estimated to contribute, if they are used, 300 to 500 additional liver grafts to the liver donor pool. [2] Obviously, these HCV-positive donors can be easily used among HCV recipients, if the recipient has not been treated pre-LT. Our initial experience has revealed higher mortality associated with pre-LT treated patients compared with pre-LT untreated patients. A 3.9 times higher 12 months mortality risk was seen for a pre-LT-treated group compared to a pre-LT-untreated group, providing a survival advantage in deferring post-transplant therapy period. [3] This is thought to be due to the fact that pre-LT recipients treated with direct acting anti-viral drugs (DAA’s) did not have access to younger HCV-positive grafts. Our thinking about holding off the pre-LT HCV treatment has changed with the first report of successful treatment of HCV in a pre-LT HCV-treated recipient who received HCV-positive younger graft due to the urgency of transplantation, due to Hepato-Pulmonary Syndrome. [4] The expected concern with the use of HCV positive grafts to HCV RNA negative recipients is the deliberate transmission of infection and its consequences. Therefore, the goal is to tackle the soaring LT waiting-list mortality by putting these HCV-positive grafts into use in such a way that the transmission of the donor infection is controlled/treated, and transplant outcomes are similar to that of an HCV negative donor. [5]