Entecavir Is Safe and Effective As Prophylaxis for Reactivation of Hepatitis B Virus in Allogeneic Stem Cell Transplant Recipients with Chronic or Resolved Viral Hepatitis B Infection
Authors: Tsuji Masanori , Ota Hikari , Nishida Aya , Ishiwata Kazuya , Yamamoto Hisashi , Yamamoto Go , Asano-Mori Yuki , Uchida Naoyuki , Izutsu Koji , Masuoka Kazuhiro , Wake Atsushi , Makino Shigeyoshi , Yoneyama Akiko , Taniguchi Shuichi 
Published: October 2019

Abstract
Abstract 4144
Hepatitis B virus (HBV) reactivation is a serious complication for allogeneic stem cell transplant (alloSCT) recipients which sometimes results in lethal hepatic failure. Lamivudine has widely been used as a prophylaxis, but the virus tends to acquire resistance to lamivudine by its long-term use. Entecavir is another nucleoside analogue with selective activity against HBV, and is known to induce less resistance to itself. Although there are several reports about lamivudine, anti-HBV immunoglobulin, and donor vaccination as prophylaxis for HBV reactivation in alloSCT recipients, only few reports about entecavir available so far. We retrospectively analyzed 191 alloSCT recipients (227 transplants) having chronic or resolved HBV infection from January 2005 to December 2011 in Toranomon Hospital. One hundred and forty (64%) cases were male, disease status of 170 (78%) cases was in high risk, and reduced-intensity conditioning regimens were selected in 177 (80%) cases. Related PBSCT, unrelated BMT, and unrelated CBT were 28 cases, 50 cases, 149 cases, respectively, and all the donors were free of HBV infection. Chronic HBV infection (18 cases) was defined as HBsAg-positive, and resolved HBV infection (209 cases) was defined as HBsAg-negative and positive for HBsAb and/or HBcAb before alloSCT without history of HBV vaccination. In recipients with chronic HBV infection, 12 cases had high serum HBV-DNA levels (more than 3 log copies/mL) before alloSCT. Antiviral agents were administered as prophylaxis for HBV reactivation in all cases with chronic HBV infection (entecavir 18 cases) and 140 (67%) cases with resolved HBV infection (lamivudine 12 cases and entecavir 128 cases). The dose of entecavir was 0.5 mg/day, and that of lamivudine was 100 mg/day. Antivirals were started before conditioning therapy, and were continued as long as the patients tolerated oral medication. Cumulative incidence of neutrophil engraftment was 90%. Two-year overall survival was 42%. About OS and neutrophil engraftment, there were no significant difference between entecavir, lamivudine, and non-prophylaxis group. Liver damages (transaminase more than 3 × upper normal limits) occurred in 80 cases, and cumulative incidence of sinusoidal obstructive syndrome was 2.2%. HBV was reactivated in 4 cases with resolved HBV infection and no cases with chronic HBV infection. The median duration of HBV reactivation from alloSCT was 326 days (250–1855). All 4 cases received unrelated RIC-CBT and had received no prophylactic antivirals, while none of those received prophylaxis developed viral reactivation. Immunosuppressants had been discontinued in all of them at the time of HBV reactivation. Two cases developed acute hepatitis, and successfully treated with entecavir and steroids. In other 2 cases, reversed sero-conversion occurred, but they did not develop hepatitis by starting entecavir. In conclusion, entecavir as prophylaxis for HBV reactivation in alloSCT recipients is considered to be safe and effective in this analysis. When to stop entecavir administration is the next issue to be investigated.

Disclosures:
No relevant conflicts of interest to declare.