title: Entecavir and hepatitis B immune globulin in patients undergoing liver transplantation for chronic hepatitis B.
abstract: For patients undergoing liver transplantation (LT) for hepatitis B virus (HBV)-related liver disease, the current standard of care for preventing reinfection of the allograft is nucleoside analogue therapy combined with hepatitis B immune globulin (HBIG). Entecavir has demonstrated high efficacy and a favorable safety profile for chronic hepatitis B (CHB) treatment, but data for patients undergoing HBV-related LT are limited. This study assessed the safety and efficacy of entecavir combined with various HBIG regimens after CHB-related LT. In this phase 3b, single-arm, open-label study, 65 patients undergoing LT for CHB-related liver disease with an HBV DNA load <172 IU/mL at LT received entecavir (1.0 mg daily) for 72 weeks after LT. The primary endpoint was the proportion of evaluable patients (treated for ≥4 weeks) with virological recurrence (HBV DNA level ≥50 IU/mL) through week 72. Concomitant HBIG therapy was received by 64 of the 65 enrolled patients, and 44% of these patients received high-dose HBIG (any HBIG dose in the specified interval ≥10,000 IU). Through week 72, all 61 patients evaluable for the efficacy analysis had undetectable HBV DNA. The Kaplan-Meier estimate of patients without hepatitis B surface antigen (HBsAg) recurrence at week 72 was 0.9655. Two patients experienced a reappearance of HBsAg, but both remained HBV DNA(-) until the last follow-up. The frequency and nature of adverse events were consistent with those expected for this patient population. Serum creatinine increments ≥0.3 mg/dL and ≥0.5 mg/dL occurred in 62% and 39% of the patients, respectively, and all of these patients received calcineurin inhibitor therapy. In conclusion, in this population of patients treated with entecavir after CHB-related LT, entecavir was well tolerated and effective in maintaining viral suppression, even in individuals who experienced a reappearance of HBsAg.
authors.affiliation: Hepatology Division, Baylor University Medical Center, Dallas, TX 75246, USA. roberper@baylorhealth.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Perrillo
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Francois
authors.initials: F
authors.lastname: Durand
authors.forename: Michael
authors.initials: M
authors.lastname: Charlton
authors.forename: Adrian
authors.initials: A
authors.lastname: Gadano
authors.forename: Guido
authors.initials: G
authors.lastname: Cantisani
authors.forename: Che-Chuan
authors.initials: CC
authors.lastname: Loong
authors.forename: Kimberly
authors.initials: K
authors.lastname: Brown
authors.forename: Wenhua
authors.initials: W
authors.lastname: Hu
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Lopez-Talavera
authors.forename: Cyril
authors.initials: C
authors.lastname: Llamoso
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000097:blood; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000628:therapy*; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use*; D017093:Liver Failure / Q000628:therapy; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged
chemical_list: D000998:Antiviral Agents; D065095:Calcineurin Inhibitors; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D007136:Immunoglobulins; C413685:entecavir; D006147:Guanine; D003404:Creatinine; C045213:hepatitis B hyperimmune globulin