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

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…151 In selected patients, ETV prophylaxis without HBIG has been shown to be safe and effective in preventing HBV recurrence. 152 Conversely, lifelong combination therapy should be given to patients who are at a high risk for HBV recurrence, namely those who are HBV DNA positive at the time of liver transplantation, who are HBeAg-positive, have HCC, and HDV or HIV co-infection. [153][154][155] In the setting of liver transplantation, nephrotoxicity should always be considered and renal function should be carefully monitored because of the concomitant use of calcineurin inhibitors.…”

How to improve long‐term outcome after liver transplantation?

“…The safety profile of tenofovir and entecavir is good with an especially low rate of resistance. There is no evidence that a combination of antiviral agents plus HBIGs is better than antiviral agents alone . Recurrence of hepatitis B virus (HBV) infection is now a very uncommon scenario.…”

The future of liver transplantation for viral hepatitis

“…Hepatocellular carcinoma has been the main indication for transplantation in HBV‐infected patients since nucleot(s)ide analogues (NUCs) now prevent progression to cirrhosis or decompensation of cirrhosis in most cases. Long‐term administration of entecavir or tenofovir after transplantation is highly effective at preventing recurrence of HBV infection . Most centres continue to use high genetic barrier NUCs in combination with anti‐HBsAg immunoglobulin (HBIg).…”