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.

Figure 1

Screening, treatment, and follow-up of the study patients. *The reasons included the following: no longer meeting the study criteria because of changes in disease status and/or LT eligibility since the initial screening (n = 23), administrative reason by the sponsor (n = 9), withdrawal of consent (n = 6), death (n = 2), noncompliance (n = 1), and other (n = 3). †The reasons included the following: death (n = 2) and no longer meeting the study criteria (n = 2: one subject required retransplantation and was discontinued by the investigator, and the other subject had an HBV viral load > 172 IU/mL at the baseline). ‡The reasons included the following: death (n = 2), noncompliance (n = 2), and other (n = 2). §Entecavir (n = 53) and lamivudine (n = 3).

Figure 2

Kaplan-Meier plot of the proportion of evaluable patients without HBsAg recurrence. BL, baseline.