New Insights in Recurrent HCV Infection after Liver Transplantation

Hsu, Shih-Hsien; Yeh, Ming-Lun; Wang, Shen-Nien

HCV reinfection of the graft is almost universal among recipients with active infections at the time of transplantation [52] . An accelerated progression of fibrosis is noted in those recipients with recurrent HCV after transplant, and at least 25 to 30% of patients will eventually develop liver cirrhosis within 5 to 10 years [53, 54] . Once liver cirrhosis is established, the first episode of decompensation may occur in as high as 40% of patients within 1 year. Apart from the rapid progression of fibrosis, recipients with recurrent hepatitis C may also develop severe fibrosing cholestatic hepatitis, characterized by jaundice, rapidly after organ transplantation in the absence of biliary obstruction causing a very high risk of graft failure [55] . For the reason, HCV-related recipients show a worse posttransplant outcome compared to HCV-negative recipients. A previous study which retrospectively analyzed 11036 patients with 11791 liver transplants confirmed that the HCV infection significantly impaired patient and graft survival after LT [56] . Focusing on the strategy to recurrent HCV infection after LT, three approaches have been identified according to the timing of treatment: pretransplantation antiviral therapy, posttransplantation prevention and preemptive treatment, and treatment for established reinfection. [58] . It is noteworthy that none of the patients who achieved SVR before LT developed graft reinfection in the study. In addition to the relative poor efficacy, safety of pegylated IFN is another concern in patients with decompensated cirrhosis. Carrion et al. reported that 43%, 29%, and 8% of patients suffered from discontinuation, decompensation, and death during therapy [57] . Although the incidence of decompensation and death is similar in comparison to control group, treated patients suffered from a significantly higher rate of bacterial infection than control group. Child-Pugh B/C is the only independent factor associated with bacterial infection. These data suggested that patients with decompensated cirrhosis should be closely monitored during Pegylated IFN therapy and followed by experts with considerable experience. Direct acting antivirals (DAAs), including protease, polymerase or other nonstructural protein inhibitors, are the newly developed agents for HCV treatment. Current data on HCV treatment using DAA are limited in patients with cirrhosis. In the phase III trials with telaprevir and boceprevir, there were only a few patients with advanced fibrosis or compensated cirrhosis included [59] [60] [61] . Although the results from the phase III trials of telaprevir and boceprevir triple therapy showed a higher SVR rates compared to Pegylated IFN/RBV therapy in advanced fibrosis and cirrhotic patients, the severe advanced events rates were also increased in patients receiving triple therapy. The data from compassionate use of protease inhibitors in viral C cirrhosis (CUPIC) cohort also demonstrated an increased serious adverse events rates (from 30% to 51%) and discontinuation rates (from 7% to 12%) in cirrhotic nonresponders compared to the phase III trials. Another study in 20 cirrhotic patients awaiting LT demonstrated that 71% of patients achieved undetectable HCV RNA at 12 weeks with DAA triple therapy. However, 25% of patients suffered from early discontinuation, and 10% of patients had decompensation during therapy. The results suggest that triple therapy must be administered cautiously with intensive safety