Until recently, liver transplantation in patients with hepatitis B was associated with a high rate of graft loss and poor survival because of viral recurrence. 1-3 Favorable outcome following liver transplantation for hepatitis B virus (HBV)-related liver disease was made possible with long-term, high-dose, passive immunoprophylaxis using hepatitis B immune globulin (HBIG). 4,5 Hepatitis B still recurs, however, despite HBIG. Recurrence may be caused by saturation of the antibody binding capacity of HBIG by a high viral load, or by mutations in the hepatitis B surface antigen (HBsAg) molecule that render HBIG ineffective. 6,7 Overall recurrence rates with HBIG monotherapy vary from approximately 15% to 50%. 4,5,[8][9][10][11] Using a different dosing schedule, in early experience from our own institution HBV recurrence on HBIG was 44%. 12 The wide disparity in the data reflects differing patient populations, e.g., patients who are HBV-DNA-positive at the time of transplantation have higher rates of recurrence. Moreover, the different dosing regimens of HBIG are also likely to influence recurrence rates. 5,11,13 An alternative approach to preventing HBV recurrence became possible using the purine nucleoside analog reversetranscriptase inhibitor, lamivudine. Demonstration of its efficacy, in the nontransplantation setting, in suppressing HBV-DNA synthesis 14,15 led to studies using lamivudine following liver transplantation as prophylaxis against hepatitis B recurrence, 16,17 or as treatment of de novo or recurrent hepatitis B. 17,18 Although a DNA virus, HBV replicates via an RNA intermediate. As is seen in human immunodeficiency virus, 19 lamivudine escape mutations in the tyrosine, methionine, aspartate, aspartate (YMDD) locus of the HBV-DNA polymerase are increasingly being reported. [20][21][22][23] While prophylactic failures of HBIG have been treated successfully with lamivudine, there are no reports documenting successful treatment of patients with lamivudine-resistant HBV.Mechanistic evidence suggests that HBIG and lamivudine would be synergistic. By inhibiting viral replication with lamivudine, it would be less likely that the viral binding capacity of HBIG would be overwhelmed; furthermore, there would be little pressure to select for HBIG-resistant mutations in the HBsAg molecule. By providing humoral immunity, HBIG may limit viral spread, confining the virus to extraheAbbreviations: HBV, hepatitis B virus; HBIG, hepatitis B immune globulin; HBsAg, hepatitis B surface antigen; anti-HBs, antibodies against hepatitis B surface antigen; PCR, polymerase chain reaction; HCC, hepatocellular carcinoma; HBeAg, hepatitis B envelope antigen.From

This study suggests that adjuvant chemotherapy after transplantation for HCC can provide long-term cure and may improve survival, even in patients with stage III and IV disease.

Prophylactic fluconazole after liver transplantation decreases fungal colonization, prevents superficial and invasive fungal infections, and has no appreciable hepatotoxicity. Although fluconazole prophylaxis is associated with fewer deaths from fungal infection, it does not improve overall survival. Patients receiving prophylactic fluconazole require close monitoring of serum cyclosporine levels to avoid neurologic toxicity.

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