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Prophylaxis of HCV reinfection and direct‐acting antiviral agents during liver transplantation

In the setting of liver transplantation (LT), the ideal timing of hepatitis C virus (HCV) infection treatment with new direct-acting antivirals agents (DAAs) has not been fully established yet. International guidelines suggest the eradication of the HCV infection before LT or the treatment of HCV recurrence after LT. Recently, Gutierrez et al. described their experience in treating LT recipients with recurrent HCV infection with direct-acting antiviral agents (DAAs), starting at different moments after the procedure (median time after LT, 5.4 years). In particular, there is no clear consensus on what treatment should be administered at the time of surgery or immediately after LT to avoid graft infection or reinfection in patients with detectable HCV RNA viremia at the time of LT (because treatment was not performed or not completed before). The time of surgery, when the hepatectomy is completed but the new liver is not yet revascularized (the socalled “anhepatic phase”), would ideally represent a unique window where the compounds would act as a prophylactic intervention rather than a curative one. However, treatment with DAAs starting from the anhepatic phase is not considered in the current guidelines. Given the efficacy, tolerability, and limited drug-drug interactions of DAAs, this absence of clear recommendations on when to start the treatment with DAAs could be detrimental for a significant number of patients. In 2014, 2 human immunodeficiency virus (HIV)– infected patients with HCV-related end-stage liver disease and detectable HCV RNA viremia, who were on the waiting list for LT at our center, were granted access to the new DAAs at the same time the liver graft became available. In both cases, treatment with DAAs was started during the anhepatic phase (Table 1). The treatment was well tolerated with no evidence of toxicity and/or interactions with the immunosuppressant drugs that were used. In the first patient (male, genotype 3a, sofosbuvir/ribavirin), the infection was eradicated after only 3 months of treatment; in the second patient (female, genotype 1b, sofosbuvir/daclatasvir), the viral load was undetectable after 2 weeks of treatment, and it is still undetectable at the last control (4 to 6 months of scheduled treatment). To the best of our knowledge, these are the first HIV-HCV coinfected patients successfully treated with DAAs starting from the anhepatic phase. Until the use of DAAs is truly universal and easily accessible, a number of patients will continue to undergo transplantation with detectable HCV RNA viremia and the certainty of HCV recurrence. During this transition period, therefore, likewise to what is a consolidated practice for patients undergoing LT for hepatitis B virus, establishing the definition of the most appropriate therapeutic approach at the time of LT or immediately after LT would be of paramount importance.