title: Evolving experience of hepatitis B virus prophylaxis in liver transplantation.
abstract: Passive immunoprophylaxis with hepatitis B immunoglobulin (HBIG) is important to prevent recurrence of hepatitis B virus (HBV) after orthotopic liver transplantation (OLT) for chronic HBV cirrhosis. With availability of lamivudine (3TC), the use of combination prophylaxis with long-term HBIG/3TC has been shown to prevent short-term HBV recurrence. This report compares HBV recurrence rates between groups receiving no/short-term HBIG, long-term HBIG alone, or HBIG/3TC prophylaxis, and describes HBIG requirements during the first 6 and 12 months in the latter two groups. This study involved patients undergoing OLT at the University of Tennessee-Memphis between May 1990 and July 2001. During this period, 388 liver transplants were performed at our center. All hepatitis B surface antigen (HBsAg)-positive recipients (n = 27) were included in this retrospective analysis. The groups were similar with regard to pre-transplant demographic characteristics such as age, gender, weight, and pre-transplant diagnosis. Owing to the retrospective study design, median follow-up was longer for the no-prophylaxis (5.6 years) and the HBIG-alone (6.0 years) groups compared to the HBIG/3TC group (4.2 years). Patient survival was 50% in the no-prophylaxis and 71% in the HBIG-alone groups compared to 100% in the HBIG/3TC group (P = 0.09). When censored for death with a functioning graft, graft survival was 50% in the no-prophylaxis and 86% in the HBIG-alone group compared to 100% in the HBIG/3TC group (P = 0.07). The overall incidence of HBV recurrence in the no-prophylaxis era was 100% and 21% in the HBIG-alone era compared to 0% in the HBIG/3TC era (P < 0.001), despite similar mean and median HBIG trough titers in the HBIG-alone and HBIG/3TC groups. The incidence of HBV recurrence in HBV DNA-positive recipients was 100% in the no-prophylaxis era, 30% in the HBIG-alone era, and 0% in the HBIG/3TC era (P < 0.001). Recipients in the HBIG-alone group had a nearly two-fold increase in HBIG requirement at 6 and 12 months in order to maintain similar HBIG trough titers post-transplant compared to recipients in the HBIG/3TC group despite similar pre-transplant HBV serology. This increased HBIG requirement in the HBIG-alone group resulted in a marked increase in the mean overall cost of HBV prophylaxis in this group ($47,367 US dollars at 6 months; $84,280 US dollars at 12 months) compared to the HBIG/3TC group ($25,931 US dollars at 6 months; $49,599 US dollars at 12 months). These data demonstrate an improvement in patient and graft survival rates in the group receiving combination HBIG/3TC prophylaxis compared to the HBIG-alone and no-prophylaxis groups. There was a significant reduction in HBV recurrence in the group receiving combination HBIG/3TC when compared to the groups receiving HBIG alone or no prophylaxis. Furthermore, we demonstrated that the addition of 3TC to the long-term HBIG regimen led to elimination of the disparity previously described in HBV recurrence rates between HBV DNA-positive and HBV DNA-negative recipients. Importantly, our data demonstrates a complete lack of HBV recurrence in the HBIG/3TC group at a median follow-up of 4.2 years. Additionally, the data show that the addition of 3TC to the post-operative prophylaxis regimen resulted in a reduction in the requirement of HBIG at 6 and 12 months, which markedly reduced the overall cost of post-transplant HBV prophylaxis.
authors.affiliation: Department of Pharmacy, Division of Transplant, University of Tennessee-Memphis, 956 Court Avenue, Memphis, TN 38103, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Honaker
authors.forename: M H
authors.initials: MH
authors.lastname: Shokouh-Amiri
authors.forename: S R
authors.initials: SR
authors.lastname: Vera
authors.forename: R R
authors.initials: RR
authors.lastname: Alloway
authors.forename: H P
authors.initials: HP
authors.lastname: Grewal
authors.forename: K L
authors.initials: KL
authors.lastname: Hardinger
authors.forename: A T
authors.initials: AT
authors.lastname: Kizilisik
authors.forename: T
authors.initials: T
authors.lastname: Bagous
authors.forename: J
authors.initials: J
authors.lastname: Trofe
authors.forename: R J
authors.initials: RJ
authors.lastname: Stratta
authors.forename: M F
authors.initials: MF
authors.lastname: Egidi
authors.forename: A O
authors.initials: AO
authors.lastname: Gaber
mesh_terms: D000328:Adult; D018890:Chemoprevention; D004359:Drug Therapy, Combination; D005260:Female; D006509:Hepatitis B / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D007136:Immunoglobulins / Q000008:administration & dosage*; D015994:Incidence; D019259:Lamivudine / Q000008:administration & dosage*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*
chemical_list: D007136:Immunoglobulins; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C045213:hepatitis B hyperimmune globulin