Risk factors and management of hepatitis C recurrence after liver transplantation

Introduction Liver disease associated with Hepatitis C virus infection is the most common indication for liver transplantation. Patients with detectable hepatitis C virus ribonucleic acid at the time of liver transplantation inevitably experience graft re-infection. This results in 30% of patients to develop cirrhosis in 5 years post liver transplantation, with a rate of decompensation at 1 year of 40%. Achievement of sustained virological response is associated with stabilisation of fibrosis and improvement in graft survival. Standard antiviral therapies using pegylated interferon, ribavirin and retransplantation in decompensated patients were the only options for the treatment. Direct acting antivirals such as protease inhibitors, polymerase or other non-structural protein inhibitors are new modalities of treatment of Hepatitis C. However, their use in the field of liver transplant is limited due to their safety and tolerance issues. Combination therapy with telaprevir or boceprevir added to pegylated interferon and ribavirin is anticipated to be beneficial but with increased rates of adverse effects and challenges in managing drug–drug interactions between the protease inhibitors and calcineurin inhibitors or sirolimus. The aim of this review was to discuss the risk factors and management of hepatitis C recurrence after liver transplantation. Conclusion Hepatitis C virus recurrence is a serious complication in liver transplant patients, where it can cause cirrhosis, graft loss and death in up to 30% of Hepatitis C virus-infected patients. Several strategies to control and minimise the Hepatitis C virus re-infection have been evolving. Direct acting antiviral represents a new era in Hepatitis C virus treatment; however, careful evaluation for drug– drug interactions, tolerance and adverse effects are required. Introduction Chronic hepatitis C is one of the leading causes of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) worldwide and the main indication for liver transplantation (LT). This reflects the changes in prioritisation of HCC for LT and an increased prevalence of HCC in the Hepatitis C virus (HCV)-infected patients1. Post LT HCV recurrence is universal in patients with detectable serum Hepatitis C virus ribonucleic acid (HCV RNA) at the time of transplantation. The 5-year graft and patient survival rates are 23% lower in HCV-infected LT recipients compared to nonHCV-infected recipients2. The most successful approach to the treatment of recurrent HCV is eradication of the HCV infection with either pre-transplant or post-transplant antiviral therapy, before hepatic decompensation occurs. Nonetheless, these patients commonly develop hepatic decompensation, and antiviral therapy is associated with poor tolerability in pre-transplant patients. Furthermore, it is associated with decreased drug efficacy and an increased risk of adverse effects in post-transplant patients3. In this article, we will review the natural history of HCV disease in LT recipients, identification of risk factors, current and future advances in the treatment of HCV recurrence. Discussion The authors have referenced some of their own studies in this review. These referenced studies have been conducted in accordance with Declaration of Helsinki (1964) and the protocols of these studies have been approved by the relevant ethics committees related to the institution in which they were performed. All human subjects, in these referenced studies, gave informed consent to participate in these studies. Natural history of HCV recurrence HCV infection of the allograft occurs at the time of transplantation and HCV RNA is detectable in the first post-operative week. The natural history of HCV disease is accelerated in post-transplant recipients compared to pre-transplant patients, presenting with high HCV RNA levels3. The HCV RNA levels progressively increase and peak at the fourth post– operative month4. Acute hepatitis develops between 1 and 4 months. Chronic hepatitis develops at 2–4 months. Cases with severe HCV recurrence have been described as early as the ninth post-operative day5. About 10% of patients develop severe disease with cholestatic features with the first year post LT, which can lead to graft loss6. Between 20% and 30% of patients develop cirrhosis within 5 years after LT and the rate of decompensation is 40% within the *Corresponding author Email: smukherjee1168@gmail.com 1 Creighton University Medical Center, Suite 5107, 601 N 30th Street, Omaha NE 68131 2 Division of Gastroenterology-Hepatology, 983285 Nebraska Medical Center, Omaha NE 68198-3285