Use of HCV-infected Organs in Solid Organ Transplantation

An Ethical Challenge But Plausible Option

Gayatri Nangia; Kelly Borges; K. Rajender Reddy

Disclosures

J Viral Hepat. 2019;26(12):1362-1371. 

In This Article

Liver Transplantation With HCV-positive Organs

In many parts of the United States, waiting time for a liver transplant is over 3 years.[33] In addition, while there was an increase in the number of liver transplants performed from 2016 to 2017, the number of people added to the liver transplant waiting list increased to around 11 500.[33] Further, recent estimates suggest that end-stage liver disease due to non-alcoholic steatohepatitis (NASH) will place an increasing burden on the liver transplant waiting list.[34] While data indicate a decreasing burden of chronic liver failure (CLF) due to HCV as a result of the advent of DAAs, there has been a simultaneous increase in the percentage of patients listed for NASH, rising at nearly the same rate as the decline in HCV induced CLF.[34] Additionally, listings due to alcoholic liver disease (ALD) have grown at a surprising rate and listings due to HCC caused by HCV increased from 2003 to 2015, reflecting that the benefit of HCV treatment in preventing HCC is more delayed.[34] Thus, the changing landscape of liver transplant waiting lists and the growth in the number of waitlist registrants exemplifies the necessity to expand the donor pool for liver transplants. One way to do this is by using HCV-positive livers for both HCV-infected and uninfected recipients.

In contrast to the data available on HCV-positive kidney transplantation, there is a dearth of data on the safety and efficacy of transplanting HCV-positive donor livers into HCV-uninfected recipients. There are two basic reasons for the lack of data: (a) HCV-positive livers are typically given to recipients who are already HCV-positive and (b) HCV-infected livers are often unsuitable as grafts because most have some degree of liver disease. Although the advent of DAA therapy has made HCV treatment significantly more safe and effective, some patients seeking liver transplants are not treated for HCV because physicians are concerned with placing them in what is often called 'MELD purgatory'.[35] A patient's Model for End-Stage Liver Disease (MELD) score is an essential factor in remaining 'competitive' for an organ offer. Treating an infected transplant candidate for HCV can lower their MELD score, placing them in a difficult position, referred to as 'MELD purgatory', in which their MELD score is no longer high enough to receive an organ offer, while, at least some, remain too sick to function adequately.

Much of the data on HCV-positive liver transplantation have been limited to comparing the outcomes between HCV-positive recipients who received HCV-positive donor organs and HCV-positive recipients who received uninfected donor organs. A multivariate analysis looked at the long-term outcomes of using HCV antibody positive liver grafts in HCV-positive recipients using data from transplants that took place between 1994 and 2008 (496 HCV+ recipients and 934 HCV+ donors).[36] It is notable that these data come from the era of IFN-based therapy, when treatment was significantly less effective and resulted in challenging adverse events, leaving HCV-positive recipients at risk for progressive liver disease. In spite of these risks, transplantation with an HCV-positive donor liver did not increase a recipients' risk of death compared to transplantation with an HCV-negative donor liver.[36] More recently, in the era of DAA-based therapy, the incidence of HCV transmission was assessed when liver grafts from HCV antibody positive donors who were non-viremic (NAT negative) were transplanted in HCV antibody negative (n = 25) or NAT-negative recipients (n = 1).[37] HCV transmission occurred in four of the patients (16%) and all of these donors had died from drug overdose.[37] Three of these patients were treated with DAAs and one died prior to being treated after a complicated postoperative course.[37] Two of the three patients treated achieved SVR12, while the third had end of treatment response but SVR12 results were still pending at publication.[37] A recent prospective analysis of 10 patients who received livers from NAT-positive donors found that all patients developed HCV infection and achieved SVR12 with DAAs.[38] Seven of these recipients had been treated for HCV prior to liver transplantation but were non-viremic at the time of transplantation.[38] There were no cases of graft loss or death and thus there were acceptable short-term outcomes.[38] While these data are promising (Table 2), larger prospective studies with longer-term follow-up are necessary to understand the risk of transplanting HCV-viremic livers into non-viremic recipients.

Furthermore, this strategy of HCV-positive liver transplantation could not only help decrease overall wait times for liver transplant, but could also specifically help patients in 'MELD purgatory'. Since MELD score plays a major role in determining which patients receive a liver transplant, centres could prioritize giving HCV-infected organs to (a) patients who are already infected with HCV, as discussed above, and (b) patients who have a low MELD score but disease severity that impairs their quality of life. Transplanting HCV-infected organs into HCV-uninfected patients with a low MELD score, but with decompensations like recurrent ascites, could help improve the quality of life of these patients, who would otherwise be deemed 'not sick enough' to receive a transplant.

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