Good virologic efficacy was seen with both single- and dual-agent DAA therapy, with rapid virologic responses of 61% and 67% and early virologic responses of 98% and 98%. Of the 52 patients given single-agent DAA treatment, 22 had a transplant and one patient had a posttransplant relapse. Of the remaining 30 patients on the transplant list, four relapsed. Nineteen of 51 patients given dual-DAA therapy were transplanted and there was one relapse, with no relapses in the 32 patients who remained on the transplant list.
After about 60 weeks of follow-up, one in three patients were “inactivated” and not considered in urgent need of a transplant, but inactivation occurred as early as 12 weeks after DAA therapy, Dr. Belli observed.
Inactivation was associated with a 3.3 decrease in MELD score, a 2-point reduction in Child-Turcotte-Pugh score, and a 0.5-g/dL increase in serum albumin after 24 weeks. There was also regression or improvement in ascites and hepatic encephalopathy in most patients. The median time of delisting was 48 weeks.
These results suggest that there could be a wider role for DAA therapy even in the sickest of HCV-positive patients who are urgently awaiting a liver transplant. Another approach to increase the number of people receiving a transplant is to use HCV-positive livers. The practice has been increasing over the years, but it is not known if the approach is safe and if the risks outweigh the benefits.
To investigate, Dr. Stepanova and associates obtained data from the Scientific Registry of Transplant Recipients (SRTR) on all liver transplants performed in the United States between 1995 and 2003 involving HCV-positive patients. A total of 37,317 records were found, of which 33,668 had data on the donors’ HCV status and on the recipients’ mortality status. Of these, 1,930 (5.7%) had received a liver from an HCV-positive donor. Dr. Stepanova noted that there had been an increase in the percentage of patients who had received an HCV-positive liver, from less than 3% in 1995 to more than 9% in 2013.
Compared with HCV-negative donors, HCV-positive donors were older, were more likely to have a history of drug abuse, and more likely to be non–heart beating at the time of procurement.
The HCV-positive liver recipients also tended to be older, to be of African-American ethnicity, and to have liver cancer but lower MELD scores than those who received an HCV-negative liver. “So these are patients that cannot wait for a long time so maybe elect to use an HCV-positive donor,” Dr. Younossi said.
Adjusted hazard ratios (aHR) showed no statistically significant difference in posttransplant survival or posttransplant graft loss between HCV-positive and HCV-negative livers; aHR were a respective 1.03 and 0.905, with tight 95% confidence intervals. However, a more recent year of transplant did appear to suggest a possible advantage of using an HCV-positive donor liver in an HCV-positive patient, with lower mortality (aHR = 0.978 per year, P less than .0001) and graft failure (aHR = 0.960 per year, P less than .0001) rates.
While the use of HCV-positive livers in HCV-positive recipients was felt to be “reasonably safe,” these findings “cannot be used in support of indiscriminate use of HCV-positive donors,” Dr. Stepanova observed. Further studies are needed to establish criteria on which to select donors that would provide patients with the best possible risk-to-benefit ratio, she said.
Further avenues for research would also be to see if HCV-positive livers could be given to HCV-negative patients and if genotype matters. It would also need to be seen if posttransplantation antiviral treatment would be necessary.
Dr. Belli has received research support from Gilead, AbbVie and BMS and acted as a consultant to Gilead. Dr. Stepanova did not have conflicts of interest to disclose. Dr. Younossi has acted as a consultant to BMS, AbbVie, Gilead, GlaxoSmithKline, and Intercept. Dr. Castera and Dr. Karlsen had no conflicts of interest to disclose.
