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After the Direct-acting Antivirals Are Gone, There Is Still Work to Be Done in the Liver.

76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 Hwithout hepatocellular carcinoma is the most common indication for orthotopic liver transplantation (OLT) worldwide. Recurrence of hepatitis C posttransplantation has been associated with accelerated graft loss and less frequently with the difficult to manage fibrosing cholestatic hepatitis. Historically, multiple strategies have been undertaken to prevent reinfection of the graft after OLT, but the toxicities of interferon made therapy for hepatitis C in a decompensated patient highly problematic. However, the all-oral direct-acting antiviral (DAA) era that began in December 2013 with the approval of sofosbuvir and ribavirin has revolutionized hepatitis C therapy in the transplant and nontransplant settings. The optimal management of the patient with hepatitis Crelated cirrhosis with or without transplant as an option remains problematic. Multiple strategies have been adopted, including DAA therapy to achieve a sustained virologic response (SVR) before and proceeding with OLT if no improvement, proceeding with OLT without therapy, treating hepatitis C to clear HCV RNA virus before OLT to minimize reinfection of the new graft, and no therapy if liver disease is advanced. All of these strategies have strengths and weaknesses depending on availability of DAAs, expected waiting time on the transplant list, as well as having the availability of OLT or not as an option. The report in this issue of Gastroenterology provides important insights into intrahepatic viral kinetics in patients with hepatitis C related cirrhosis who receive DAA therapy before OLT. Gambato et al measured HCV RNA in explants by polymerase chain reaction (PCR) from 39 patients who received antiviral therapy before OLT. The clinical outcomes of these patients have been previously reported with 33 of 39 individuals achieving posttransplant virologic response (pTVR), and 6 patients relapsing after transplantation. They noted HCV RNA was still detected in explants by PCR testing in two-thirds of the individuals (22 of 33) who achieved pTVR as well as 4 of 6 individuals who relapsed after OLT. In the 39 individuals who had undetectable serum HCV RNA, a similar pTVR was achieved regardless of whether or not intrahepatic HCV RNA was detected. Only 6 of 39 individuals had completed antiviral therapy at the time of OLT and all of the patients included in this analysis had not yet achieved SVR, giving clinicians a window to the intrahepatic