HEPATITIS-B AND LIVER-TRANSPLANTATION

Liver transplantation in hepatitis B virus (HBV)-infected patients is very commonly followed by recurrence of infection in the transplanted liver. Most recipients with HBV recurrence will develop chronic hepati tis that follows a more aggressive course than is seen in non-immuno-c ompromized subjects and this frequently results in graft failure. The presence of hepatitis B e antigen or significant levels of HBV-DNA in the serum is highly predictive of recurrence and this has led to the v iew that patients, whose serum is positive for these conventional mark ers of replication, should be excluded from transplantation. The key t o improving the results of transplantation in patients with HBV infect ion lies in the development of effective strategies to prevent reinfec tion. High dose anti-HBs immunoglobulin is effective in patients who a re coinfected with hepatitis D, those transplanted for fulminant hepat itis and cirrhotic patients who have very low levels of viral replicat ion prior to transplantation. Unfortunately, immunoprophylaxis does no t seem to influence the outcome in those patients with higher levels o f replication. There are several new orally active nucleoside analogue s that are potent inhibitors of hepatitis B replication that may be ef fective for both the prevention and treatment of recurrent disease. Th e most promising are lamivudine (2',3',dideoxy,3',thiacytidine) and fa mciclovir (a guanosine analogue). Both agents have been extensively ev aluated in animal models of HBV and have been shown to rapidly suppres s viral replication, The initial experience with these agents in liver transplant recipients has been promising and a number of studies are currently underway to determine whether these drugs, used alone or in combination with immunoprophylaxis, are able to prevent recurrence in those patients at highest risk of post-transplant HBV recurrence.