title: Lamivudine therapy in patients undergoing liver transplantation for hepatitis B virus precore mutant-associated infection: high resistance rates in treatment of recurrence but universal prevention if used as prophylaxis with very low dose hepatitis B immune globulin.
abstract: Recurrent hepatitis B virus (HBV) infection remains a major cause of morbidity and mortality after liver transplantation. Recently, antiviral therapy, such as lamivudine, has become available for prophylaxis against HBV reactivation posttransplantation and for the treatment of HBV recurrent disease. We report our initial experience with lamivudine therapy in patients with precore mutant-associated HBV infection undergoing liver transplantation (n = 29). Outcomes were compared in three patient groups: group 1, precore mutant HBV infection not receiving lamivudine (n = 10); group 2, recurrent precore mutant HBV infection posttransplantation subsequently treated with lamivudine (n = 10); and group 3, HBV precore mutant patients undergoing liver transplantation and receiving lamivudine and low-dose hepatitis B immune globulin (HBIG) from the time of transplantation (n = 9). In group 1, HBV recurred in 9 of 10 patients, with subsequent graft loss in all 9 patients. In group 2, all patients developed HBV recurrence at a mean of 7.3 months posttransplantation and started lamivudine therapy at a median of 16 months posttransplantation. Follow-up on lamivudine therapy was for a median of 11 months. Six of these 10 patients developed mutations in the HBV polymerase gene associated with lamivudine resistance. There were two liver failure-related deaths in this group. In group 3 patients, there was one death from graft-versus-host disease. The remaining 8 patients have been followed up for a mean of 15.6 months posttransplantation, and all remain hepatitis B surface antigen negative and HBV DNA negative. In conclusion, lamivudine therapy in association with low-dose HBIG is effective in preventing HBV reactivation posttransplantation. Rescue therapy with lamivudine in patients with HBV recurrence is only moderately effective, with a 60% lamivudine resistance rate in patients treated for longer than 6 months.
authors.affiliation: A.W. Morrow Gastroenterology and Liver Centre, Australia.
authors.forename: G W
authors.initials: GW
authors.lastname: McCaughan
authors.forename: J
authors.initials: J
authors.lastname: Spencer
authors.forename: D
authors.initials: D
authors.lastname: Koorey
authors.forename: S
authors.initials: S
authors.lastname: Bowden
authors.forename: A
authors.initials: A
authors.lastname: Bartholomeusz
authors.forename: M
authors.initials: M
authors.lastname: Littlejohn
authors.forename: D
authors.initials: D
authors.lastname: Verran
authors.forename: A K
authors.initials: AK
authors.lastname: Chui
authors.forename: A G
authors.initials: AG
authors.lastname: Sheil
authors.forename: R M
authors.initials: RM
authors.lastname: Jones
authors.forename: S A
authors.initials: SA
authors.lastname: Locarnini
authors.forename: P W
authors.initials: PW
authors.lastname: Angus
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control / Q000601:surgery*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007116:Immunization, Passive; D007136:Immunoglobulins / Q000008:administration & dosage*; D019259:Lamivudine / Q000627:therapeutic use*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012008:Recurrence; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D014758:Viral Core Proteins / Q000235:genetics
chemical_list: D007136:Immunoglobulins; D018894:Reverse Transcriptase Inhibitors; D014758:Viral Core Proteins; D019259:Lamivudine; C045213:hepatitis B hyperimmune globulin