The natural history of recurrent hepatitis C and what influences this.

1. Liver failure and liver cancer from chronic hepatitis C are the most common indications for liver transplantation and numbers of both are projected to double over the next 20 years. 2. Recurrent hepatitis C infection of the allograft is universal and immediate following liver transplantation and associated with accelerated progression to cirrhosis, graft loss and death. 3. Graft and patient survival is reduced in liver transplant recipients with recurrent HCV infection compared to HCV-negative recipients. 4. The natural history of chronic hepatitis C is accelerated following liver transplantation compared C, with 20% progressing to cirrhosis by 5 years. However, the rate of fibrosis progression is not uniform and may increase over time. 5. The rates of progression from cirrhosis to decompensation and from decompensation to death are also accelerated following liver transplantation. 6. Multiple host, donor and viral factors are associated with rapid fibrosis progression and HCV-related graft failure. 7. Over the last decade, graft and patient survival rates have improved following liver transplantation for non-HCV disease but not for HCV-cirrhosis. This may reflect worsening donor quality and changes in immunosuppression strategies over recent years. 8. Viral eradication by antiviral therapy prevents disease progression and improves survival. 9. The severity of recurrent hepatitis C at one year post-transplant predicts subsequent progression to cirrhosis. Annual protocol biopsies are recommended to help determine need for antiviral therapy. 10. The projected impact of recurrent hepatitis C on graft and patient survival can only be avoided by the development of safe and effective antiviral strategies which can both prevent initial graft infection and eradicate established hepatitis C recurrence.