COMMENTARY

Reduced Demand, Increased Supply: Innovations Are Brightening Liver Transplantation Outcomes

The Liver Meeting 2017: American Association for the Study of Liver Diseases (AASLD)

William F. Balistreri, MD

Disclosures

December 04, 2017

In This Article

Expanding the Supply

Using the Previously Unusable

As the incidence of HCV infection rises, due in part to the epidemic of injection drug use, there has been a parallel rise in the deaths of young individuals. This has resulted in an increased number of potential donor organs infected with HCV.

Anti-HCV‐positive donor livers with active infection (ie, HCV RNA positive) present a high risk for transmission of HCV; thus, under current guidelines, their use is restricted to patients on the transplant wait list with active HCV.

Anti-HCV-positive donor livers have not been transplanted into HCV-negative recipients because of adverse posttransplant outcomes associated with allograft HCV infection. However, in the era of highly effective DAA agents, the risk-benefit ratio would seemingly favor the use of these organs for transplantation.

Several centers have initiated clinical trials to assess the safety and effectiveness of transplanting livers from selected anti-HCV-positive donors. They postulated that in view of the ongoing shortage of liver grafts and the high waiting-list mortality rates, HCV-negative patients on the transplant waiting list may benefit from accepting HCV-positive organs.

Risk for HCV Transmission

An increased risk donor (IRD) is defined as one that meets the Public Health Services' criteria for a high risk for transmission of HCV infection; specifically, they are found to be anti-HCV positive but have no evidence of active HCV infection (HCV RNA negative). Transplantation of these organs to anti-HCV-negative recipients would expand the donor pool.

Bari and colleagues[5] hypothesized that because treatment is available, IRDs would present a low risk for HCV transmission, and these livers may not necessarily be discarded if an HCV-positive candidate recipient is not available. They evaluated the risk for HCV transmission from IRDs to anti-HCV-negative candidates.

Under this informed-consent protocol, 25 anti-HCV-negative candidates received HCV-IRD organs. These organ recipients underwent HCV RNA testing to determine if HCV transmission had occurred. HCV disease transmission was documented in four recipients (16%) by 3 months posttransplant. Three of these viremic patients were treated with DAAs. The investigators noted that the observed 16% rate of HCV transmission is higher than expected for the "eclipse period," the interval between infection and appearance of mature virus in serum. This raised the question as to the mode of HCV transmission. The authors suggested it to be due to occult HCV infection, defined as detectable HCV RNA in liver tissue of patients with spontaneous or treatment-induced HCV RNA clearance from serum. However, they emphasized the need for HCV genome testing to more fully understand the mechanism of transmission.

Chhatwal and colleagues[6] further modeled the potential benefit of accepting an HCV-positive organ for an HCV-negative candidate. A Markov-based mathematical model that simulated HCV-negative patients on the transplant waiting list was developed to compare long-term outcomes in patients willing to accept HCV-positive/negative livers versus those willing to accept only HCV-negative livers. Patients receiving HCV-positive livers were treated preemptively with 12 weeks of DAA therapy. Accepting HCV-positive/negative livers versus HCV-negative livers resulted in an increase in life expectancy when the Model for End-Stage Liver Disease score was ≥20. The magnitude of clinical benefit was greatest in UNOS regions with the highest HCV-positive donor rates.

Transplanting anti-HCV-positive livers into HCV-negative patients, while incorporating shared decision-making and initiating preemptive DAA therapy, could be a viable option for improving patient survival on the transplantation waiting list.

Optimizing Allocation of Grafts From Anti-HCV-Positive Donors

One concern with this strategy is the fact that the viral load is often unavailable prior to allocation because of technical issues.

Martini and colleagues[7] evaluated the value of urgent testing for serum HCV RNA in anti-HCV-positive donors to optimize liver allocation. From August 2014 to March 2016, they transplanted 11 livers from anti-HCV-positive donors who had undergone a biopsy and serum HCV RNA quantification at the time of harvesting. Seven donors were found to be HCV RNA positive and were allocated to untreated viremic recipients who underwent DAA treatment immediately after transplantation; all had undetectable levels of HCV RNA within 4 weeks. Four donors tested HCV RNA negative at transplantation, and their organs were allocated to HCV RNA-negative recipients. All 11 recipients are alive at a median follow-up of 662 days.

The investigators have demonstrated that urgent serum HCV RNA determination in anti-HCV-positive donors would allow paired donor/recipient virologic allocation, optimizing the cost-effectiveness of antiviral therapy. These data further validate the potential safety of allocation of nonviremic anti-HCV-positive organs to HCV-negative recipients.

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