Hepatitis C Virus transmission after user of viraemic donors via heart or lung graft within in a controlled study (at a calculated risk due to preemptive treatment by a pangenotypic DAAs application)

Abbreviations: HCV Hepatitis C virus; DAA direct-acting antivirals, SVR sustained virological response (no detectable HCV viremia 6 months after antiviral therapy) Wooley et al. report a single-center study of outcomes in heart and lung recipients receiving grafts from HCV viraemic donors with treatment of a preemptive short courses of direct-acting antivirals (DONATE HCV ClinicalTrials.gov number, NCT03086044.): 44 HCV seronegative recipients received organs (36 lung, 8 heart) from HCV-viraemic donors (viral load Median: 0.89 log6 IU/ml, IQR: 0.27 to 4.63 log6 IU/ml; HCV genotype: 1 in 61%, 2 in 17%, 3 in 17 %, indeterminate in 5%). All recipients received a 4 week pangenotypic combination of DAA sofosbuvir-velpatasvir, initiated immediately a few hours after transplant to prevent HCV infection (via enteral feeding). In 42 of the 44 recipients posttransplant HCV viremia (95%) became detectable, but viremia cleared within 2 weeks. All 35 patients who survived to 6 months posttransplant with functioning grafts had SVR. No drug-related serious adverse events occurred, but an insignificant increased incidence of low-grade acute cellular rejection was observed in lung recipients. The authors conclude, that in heart or lung transplant recipients an pangenotypic antiviral regimen for 4 weeks, initiated within a few hours after transplantation, can prevented establishment of HCV infection. This may decrease costs in patients treated with appropriate informed consent and education. Some limitation should be noted (see Comment of Blumberg EA): Both HCV-negative and HCV-positive donors in this trial were younger than the mean age in the current donor pool in the United States. Also, in this study recipients were less critically ill and they had a lower priority on the waiting list. The follow up period of recipients is of limited duration (<1 year) in this and other studies. Currently it is unknown, which late complications may occur or not as well as to which extend SVR can be achieved in every recipient with a short term or standard term of treatment and what is the impact of mutants. The interaction of DAA treatment in the transplantation setting needs further evaluation. Also access to these potentially lifesaving including appropriate treatment with DAA preemptively must be ensured by shareholders and stakeholders in the different healthcare systems. Beyond this the major Implications are: The opioid epidemic in some countries produces a growing number of potentially suitable donors who are HCV infected. On the other side using DAAs decreases the number of HCV-infected possible recipients. To minimize organ wastage, the transplant community started to use HCV-infected organs in HCV-negative recipients, curing and preventing infection with posttransplant DAAs. Finally the concept of post exposure pangenotypic prophylaxis with a shorter duration than 12 weeks DAA therapy may work in grafts assumed to be not a HCV reservoir (e.g. heart, lung) without determination of the genotype before therapy while taking into account the limitations mentioned above.