Chronic hepatitis C is the leading indication for adult liver transplantation in Australia, accounting for about 40% of transplants. Recurrence of hepatitis C after liver transplantation is universal and is a major clinical problem. Recurrent HCV pursues a more aggressive course after transplantation, with up to 80% of patients developing chronic hepatitis and 30% of patients progressing to cirrhosis within 5 years. Furthermore, in the setting of immunosuppression, 2%–5% of patients develop FCH within 6 months of transplantation. FCH is associated with very high-level viraemia, which is directly cytotoxic, causing rapid progression to jaundice, liver failure and death. Mortality rates of 80% are reported. Finally, although recurrent HCV infection is a major cause of allograft dysfunction after transplantation, it is not the only cause, and discrimination from other causes, including acute cellular rejection, biliary and vascular complications and drug hepatotoxicity, is challenging.
Treatment with DAAs offers the opportunity to clear HCV either before transplantation (preventing recurrence) or after transplantation (treating recurrence). Where possible, treatment should be initiated early after transplantation to prevent fibrosis progression; however, treatment is also indicated in people with established recurrence, including cirrhosis. People with FCH should be identified and treated immediately to prevent rapid progression to allograft failure.
Since the introduction of DAA treatments, most Australian patients with established HCV recurrence after liver transplantation have been treated. Issues regarding HCV and liver transplantation have shifted significantly. Patients requiring transplantation for decompensated cirrhosis associated with HCV may have been successfully treated and come to transplantation without viraemia (see treatment of decompensated liver disease). Despite viral clearance, liver function may have failed to improve in these patients, usually associated with adverse baseline factors, including ascites or encephalopathy, serum albumin level below 35 g/L, ALT level below 60 U/L, and body mass index above 25 kg/m2, which are associated with an increased risk of not achieving a reduction in Child–Pugh score to class A, or significant comorbidities (eg, alcohol use, obesity, diabetes). In other patients, antiviral treatment may have failed in association with the development of RASs. Salvage therapy with a protease inhibitor is contraindicated in this setting and must therefore be deferred until after transplantation. Antiviral treatment of HCC patients on the waiting list is controversial, with some clinicians electing to treat before transplantation and others choosing to wait until after transplantation (Direct-acting antiviral therapy and risk of hepatocellular carcinoma in people with cirrhosis).
Another issue that has emerged is the use of livers from HCV-positive donors, which were previously used only in HCV viraemic recipients. In this situation, the recipient HCV genotype should ideally be rechecked after transplantation. Increasingly, and with appropriate consent, HCV viraemic donor livers are being used in HCV-negative recipients. When an anti-HCV-positive/HCV RNA-positive donor is used, HCV infection will be transmitted and should be treated with DAAs in the early post-transplant period. Transmission from anti-HCV-positive/HCV RNA-negative donors is extremely rare and, where reported, probably reflects acute infection in high-risk donors.