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

Robert Perrillo, Maria Buti, Francois Durand, Michael Charlton, Adrian Gadano, Guido Cantisani, Che Chuan Loong, Kimberly Brown, Wenhua Hu, Juan Carlos Lopez-Talavera, Cyril Llamoso

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)887-895
Number of pages9
JournalLiver Transplantation
Volume19
Issue number8
DOIs
StatePublished - Aug 2013

Fingerprint

Chronic Hepatitis B
Hepatitis B
Liver Transplantation
Immunoglobulins
Hepatitis B virus
Hepatitis B Surface Antigens
DNA
entecavir
Liver Diseases
Safety
Recurrence
Kaplan-Meier Estimate
Therapeutics
Standard of Care
Nucleosides
Population
Allografts
Creatinine

ASJC Scopus subject areas

  • Surgery
  • Transplantation
  • Hepatology

Cite this

Perrillo, R., Buti, M., Durand, F., Charlton, M., Gadano, A., Cantisani, G., ... Llamoso, C. (2013). Entecavir and hepatitis B immune globulin in patients undergoing liver transplantation for chronic hepatitis B. Liver Transplantation, 19(8), 887-895. https://doi.org/10.1002/lt.23690

Entecavir and hepatitis B immune globulin in patients undergoing liver transplantation for chronic hepatitis B. / Perrillo, Robert; Buti, Maria; Durand, Francois; Charlton, Michael; Gadano, Adrian; Cantisani, Guido; Loong, Che Chuan; Brown, Kimberly; Hu, Wenhua; Lopez-Talavera, Juan Carlos; Llamoso, Cyril.

In: Liver Transplantation, Vol. 19, No. 8, 08.2013, p. 887-895.

Research output: Contribution to journalArticle

Perrillo, R, Buti, M, Durand, F, Charlton, M, Gadano, A, Cantisani, G, Loong, CC, Brown, K, Hu, W, Lopez-Talavera, JC & Llamoso, C 2013, 'Entecavir and hepatitis B immune globulin in patients undergoing liver transplantation for chronic hepatitis B', Liver Transplantation, vol. 19, no. 8, pp. 887-895. https://doi.org/10.1002/lt.23690
Perrillo, Robert ; Buti, Maria ; Durand, Francois ; Charlton, Michael ; Gadano, Adrian ; Cantisani, Guido ; Loong, Che Chuan ; Brown, Kimberly ; Hu, Wenhua ; Lopez-Talavera, Juan Carlos ; Llamoso, Cyril. / Entecavir and hepatitis B immune globulin in patients undergoing liver transplantation for chronic hepatitis B. In: Liver Transplantation. 2013 ; Vol. 19, No. 8. pp. 887-895.
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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.",
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