iver transplantation for patients with hepatitis B infection is rapidly changing. The initial L experience of dismal graft and patient survival rates has resulted in denial of reimbursement by many private and federal insurance carriers. This has been tempered by better selection of candidates and the use of prophylactic hepatitis B immunoglobulin (HBIG). There is general agreement that patients coinfected with delta virus, those with negative hepatitis B antigen and undetectable HBV DNA as determined by solution hybridization assay, and fulminant 8 cases, when gven a course of HBIG postoperatively are unlikely to develop recurrent hepatitis B infection. Even lower rates of recurrence are anticipated if only those patients and donor livers that are negative for HBV DNA by polymerase chain reaction (PCR) assay are selected.
Controversy continues regarding transplantation of HBeAg-positive and/or HBV DNA-positive patients. Without concomitant administration of HBIG, recurrence rates of HBV in the transplanted liver are high but even with HBIG recurrence rates are still unacceptably high unless HBIG is given in doses that maintain serum anti-HBs levels over 100 IU/mL and perhaps as high as 500 IU/mL for indefinite periods of time. Even under these circumstances, recurrence of HBV occurs in a third of the patients, Furthermore, long-term HBIG therapy, potentially for the rest of the patient's life, may present significant problems with cost, compliance, and complications.
Clearance of HBV DNA, undetectable by PCR, before liver transplantation should result in excellent posttransplantation graft and patient survival rates. Recent developments indicate that this indeed may be accomplished. New antiviral nucleoside analogues for HBV may be capable of rendering candidate patients HBV DNA-negative by PCR assay before transplantation as well as clearing HBV DNA from those patients who have undergone transplantation and who develop recurrent HBV DNA despite prophylactic HBIG therapy. Lamivudine, the negative enantiomer of 3' thiacytidine, a 2'3' didoxynucleotide, is a potent inhibitor of HBV DNA in patients with chronic viral B hepatitis. In doses of 100 mg to 300 mg taken orally once daily, sustained viral remission has been achieved in some patients who have not undergone transplantation after only 3 months of treatment with negligible side effects.' Moreover, after 20 weeks with a dose of 100 mg daily undetectable HBV DNA by PCR was achieved in a patient coinfected with human immunodeficiency virus (HIV).2 More impressive has been the observation of lamivudine induced disappearance of HBV DNA among patients who broke through prophylactic HBIG with recurrent HBV DNA following liver tran~plantation.~.~ How long lamivudine therapy will have to be continued in such patients remains to be determined.
Regardless, these highly successful preliminary results are likely to have a dramatic impact on the management of patients with chronic hepatitis B infection whether or not transplantation is indicated. Furthermore, other nucleoside analogues, eg, famciclovir, may have similar beneficial effects5 If ongoing trials of oral nucleoside analogues, used both before and after liver transplantation, prove to be highly effective in the prevention of recurrent hepatitis B infection, HBIG therapy most likely will be abandoned at least for long-term prophylaxis. Undoubtedly, the future problems of transplantation for patients with end-stage chronic hepatitis B disease will focus on a marked increase in the pool of much more suitable transplant candidates who have been successfully treated for the viremia. Until the impact of worldwide universal hepatitis B immunization results in a sharp reduction in the prevalence of this disease, we can anticipate yet even further demands for donor livers, already in relatively scare supply, to accommodate this new large group of noninfectious hepatitis B patients. Hepatitis B will no longer be a contraindication for liver transplantation.