entecavir and Graft-vs-Host-Disease

Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive patients after allogeneic hematopoietic stem cell transplantation (HSCT) has not been prospectively studied. HBsAg-negative, anti-HBc-positive patients with undetectable HBV DNA undergoing allogeneic HSCT were prospectively monitored every 4 weeks. The primary endpoint was HBV reactivation, defined as detectable HBV DNA (≥10 IU/mL). Secondary endpoints included overall survival, HBsAg positivity, and changes in liver biochemistry and antibody to HBsAg levels. Among 297 allogeneic HSCT recipients, 85 (28.7%) were HBsAg-negative, anti-HBc-positive, of whom 62 were recruited and monitored for a median of 48 (4-104) weeks. The 2-year cumulative HBV DNA detectability rate was 40.8%, occurring at a median of 44 (8-100) weeks. Multivariate analysis showed that age ≥50 years (P = 0.004, hazard ratio = 8.2) and chronic graft-versus-host disease (P = 0.010, hazard ratio = 5.3) were significantly associated with HBV reactivation. Other clinical parameters, including baseline antibody to HBsAg status, serial changes in antibody to HBsAg levels, and donor serology, were not associated with HBV reactivation. Patients <50 years old and without chronic graft-versus-host disease, compared with the remaining patient cohort, had a significantly lower 2-year cumulative HBV reactivation rate (5.6% versus 65.0%, P = 0.004). Entecavir successfully suppressed HBV DNA to undetectable levels, with no cases developing biochemical hepatitis.. HBsAg-negative, anti-HBc-positive patients had a high rate of HBV reactivation after allogeneic HSCT, with determinants of HBV reactivation including age ≥50 years and chronic graft-versus-host disease; treatment strategies based on these parameters may prevent HBV reactivation and subsequent complications. (ClinicalTrials.gov identifier NCT01481649.) (Hepatology 2017;65:1451-1461).

Topics: Adult; Age Factors; Antiviral Agents; Female; Graft vs Host Disease; Guanine; Hematopoietic Stem Cell Transplantation; Hepatitis B Core Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Recurrence; Virus Activation; Young Adult

Chronic carriers of hepatitis B virus (HBV) who have to be immunosuppressed are at risk for HBV reactivation and hepatitis. Continuing immunosuppression in such patients and in immunosuppressed patients with active hepatitis B is strongly discouraged yet frequently inevitable. We here report on both the successful control of hepatitis and seroconversion after HBV reactivation following allogeneic hematopoietic stem cell transplantation (HSCT) with entecavir despite systemic immunosuppression.

Topics: Antiviral Agents; Bronchiolitis Obliterans; Female; Graft vs Host Disease; Guanine; Hepatitis B; Hepatitis B Antibodies; Humans; Immunocompromised Host; Immunosuppressive Agents; Middle Aged; Treatment Outcome