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  • Open Access

Entecavir and hepatitis B immune globulin in patients undergoing liver transplantation for chronic hepatitis B

Authors


  • Robert Perrillo has received payment for participating in a speakers' bureau. Maria Buti has provided consultancy services and received lecture fees from Bristol-Myers Squibb and Gilead and is an advisory board member for Bristol-Myers Squibb and Gilead. Francois Durand has provided consultancy services for Novartis, Astellas, and Gilead. Adrian Gadano has received consulting fees, lecture fees, and support for travel from Bristol-Myers Squibb. Juan Carlos Lopez-Talavera, Kimberly Brown, Wenhua Hu, and Cyril Llamoso are Bristol-Myers Squibb employees. Juan Carlos Lopez-Talavera and Cyril Llamoso hold stock/stock options in Bristol-Myers Squibb. Guido Cantisani, Michael Charlton, and Che-Chuan Loong have nothing to disclose.

  • The study was funded by Bristol-Myers Squibb. Editorial support was provided by Isabelle Kaufmann of Articulate Science and was funded by Bristol-Myers Squibb.

Address reprint requests to Robert Perrillo, M.D., Hepatology Division, Baylor University Medical Center, 3410 Worth St., Dallas, TX 75246. Telephone: 214-820-2956; FAX: 214-820-0993; E-mail: roberper@baylorhealth.edu

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. Liver Transpl 19:887–895, 2013. © 2013 AASLD.

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