Hepatitis viruses and liver transplantation : Molecular biology, pathogenesis and clinics

Acute and chronic liver diseases related to hepatitis viruses are the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. The risk of viral B reinfection is: 80% in the absence of prophylaxis; is related to the presence of active viral B replication prior to transplantation; is higher in patients with chronic liver disease, rather than with fulminant hepatitis; and is higher in patients with hepatitis B virus (HBV)-related liver disease alone rather than in those with HBV-hepatitis delta virus (HDV) infection. Post-transplant long-term passive antibody to hepatitis B (anti-HB) immunoprophylaxis reduces the risk of HBV recurrence to 30% in patients with HBV cirrhosis, and to less than 10% in those with fulminant hepatitis B. Patients with HBV-HDV liver disease receiving passive anti-HB immunoprophylaxis are at low risk of HBV recurrence (10-15%), but at high risk of HDV recurrence (80%). However, HDV reinfection of the graft has no clinicopathological consequence in the absence of concomitant HBV reinfection. The five year survival of patients transplanted for HBV cirrhosis and for HDV cirrhosis at the Hepatobiliary Center, Hopital Paul Brousse is 72% and 85%, respectively. Hepatitis B virus reinfection of the graft is characterized by a high level of viral replication, and a chronic outcome. Antiviral treatments such as ganciclovir, adenine arabinoside monophosphate, famcyclovir, and lamivudine have a place after transplantation and may stop HBV replication. ganciclovir, famcyclovir and lamivudine should be continued for several months and in some cases indefinitely. Hepatitis C virus reinfection is almost constant, assessed by the persistence of hepatitis C virus (HCV)-RNA in the serum in 90% of cases. Acute lobular hepatitis appeared in 75% of patients at a median of 4 months post transplantation with a range of between 23 days and 4 years. In our series, the 5 year actuarial rate of HCV acute hepatitis on the graft, chronic hepatitis, and cirrhosis, is 75, 60, and 8%, respectively. Hepatitis C virus RNA level is dramatically increased after transplantation and seems to correlate with the occurrence of acute hepatitis on the graft. A positive relation between genotype lb and prevalence and severity of HCV hepatitis on the graft have been suggested in European series. There is no demonstrated way to prevent HCV reinfection. The use of interferon for the treatment of HCV hepatitis on the graft was disappointing due to a poor antiviral effect and the occurrence of chronic rejection episodes in some patients. Promising results of the combination of interferon and ribavirine have been reported and need confirmation. The 5 year survival of patients transplanted for viral C cirrhosis at the Hepatobiliary Center, H6pital Paul Brousse is 78%. In conclusion, patients with HBV cirrhosis and without HBV replication are candidates for liver transplantation. Long-term passive anti-HB prophylaxis is the best way to prevent HBV recurrence. Patients with HBV replication should be included in protocols using combinations of antiviral treatments and passive anti-HB immunoprophylaxis. Viral C reinfection is frequent, but medium-term survival is good. However, long-term graft and patient survival remains unknown and methods to prevent and treat HCV reinfection on the graft are needed.