Lamivudine plus low-dose hepatitis B immunoglobulin to prevent recurrent hepatitis B following liver transplantation.
OBJECTIVE
High-dose intravenous hepatitis B immunoglobulin (HBIG) may prevent recurrent hepatitis B virus (HBV) infection, but the cost has limited its widespread use in countries with endemic HBV infection. We report on long-term safety and efficacy of an alternative strategy of very low doses (400-800 IU/month) of intramuscular (IM) HBIG plus lamivudine.


METHODS
Australian and New Zealand patients who received low-dose HBIG plus lamivudine following liver transplantation for HBV-related end-stage liver disease were studied. Prior to transplantation, patients with detectable serum HBV DNA received lamivudine 100 mg daily. Posttransplantation, all patients received lamivudine 100 mg daily plus IM HBIG 400 or 800 IU daily for 1 week then monthly thereafter. Serum HBV DNA levels were measured prior to lamivudine, at transplantation, and at 12 months posttransplantation. Serum titers of antibody to HBV surface antigen were measured at 1, 3, and 12 months posttransplantation.


RESULTS
Between February 1996 and October 2004, 147 patients received low-dose HBIG plus lamivudine. Thirty-one percent were hepatitis B e antigen positive, and 85% were HBV DNA+ prior to transplantation. The median duration of pretransplantation lamivudine was 92 days (range, 1-1775). Median follow-up posttransplantation was 1860 days. Kaplan-Meier patient survival was 92% at 1 year and 88% at 5 years. The actuarial risk of HBV recurrence was 1% at 1 year and 4% at 5 years. Baseline HBV DNA titer was associated with HBV recurrence.


CONCLUSIONS
Low-dose IM HBIG plus lamivudine provides safe and effective long-term prophylaxis against recurrent HBV at <10% the cost of the high-dose regimen.
Gane
Edward J
EJ
Auckland City Hospital, Auckland, New Zealand. EdGane@adhb.govt.nz
Angus
Peter W
PW
Strasser
Simone
S
Crawford
Darrell H G
DH
Ring
John
J
Jeffrey
Gary P
GP
McCaughan
Geoffrey W
GW
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001315:Australia / Q000453:epidemiology; D004279:DNA, Viral / Q000097:blood; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000150:complications / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D006510:Hepatitis B Antibodies / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000008:administration & dosage* / Q000009:adverse effects; D007273:Injections, Intramuscular; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D008107:Liver Diseases / Q000401:mortality / Q000601:surgery / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009520:New Zealand / Q000453:epidemiology; D011183:Postoperative Complications / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D007136:Immunoglobulins; D019259:Lamivudine; C045213:hepatitis B hyperimmune globulin