Resolution of Hepatitis B Virus (HBV) Infection is Common after Antiviral Therapy in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Recipients who Develop Reverse Seroconversion
Sarah P. Hammond1,2, Vincent T. Ho2, Chinweike Ukomadu3, Lind-sey R. Baden1,2, Francisco M. Marty1,2;
1Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA; 2Dana-Farber Cancer Institute, Boston, MA; 3Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA
Background: HBV reactivation in allogeneic HSCT recipients with evidence of resolved HBV infection before transplant (also called reverse seroconversion [RS]) is a significant clinical problem which can occur years after HSCT. Clinical outcomes of allogeneic HSCT recipients who developed RS are poorly described. We undertook this retrospective study to describe clinical outcomes among those who developed RS after HSCT. Methods: We identified all allogeneic HSCT recipients with evidence of resolved HBV infection (core IgG positive, surface antigen [HBsAg] negative, HBV DNA undetectable) before HSCT who were transplanted between 1 /00 and 12/11. HBV reactivation was defined as redevelopment of HBsAg positivity. Medical records were reviewed for clinical outcomes up to 5/13. Results: Of 100 allogeneic HSCT recipients with prior HBV infection 17 (17%) developed RS after HSCT. Cumulative probability of RS was 6.2%, 12.7%, 20.7% and 31.7% at 1, 2, 3 and 4 years after HSCT. Median ALT at RS diagnosis was 83 U/L (range 13–1411). Of 17 with RS 15 had HBV DNA >10^5 IU/mL and were treated with entecavir (14) or lamivu-dine/adefovir (1). Two patients that had HBV DNA <10^5 IU/mL were observed without antiviral therapy and cleared HBsAg within a month (13 and 28 days). Of the 15 patients who were treated, one developed symptomatic hepatitis after treatment started with transient jaundice and ascites which resolved on continued antivirals. 6 of 15 (40%) cleared HBsAg at a median of 17 months (range 1–52, IQR 8–28) after antiviral therapy started. Cumulative probability of clearing HBsAg was 15.4%, 32.3%, 40.8% and 55.6% after 1, 2, 3 and 5 years of antiviral therapy. Despite negative or low HBV surface antibody at time of reactivation, all 6 who cleared HBsAg developed robust quantitative surface antibody in conjunction with HBsAg clearance: median 336 IU/mL (range 98->1000). 5 of 6 who cleared HBsAg stopped antiviral therapy within 6 months of clearance and have been followed for a median of 54 months (range 22–66) without HBV recurrence; the remaining patient is on antiviral therapy for a planned 6 month course post HBsAg clearance. 5 of 17 patients died during follow up (29%), but none died of HBV complications; causes of death included relapsed cancer, graft-versus-host disease and mucormycosis. Conclusions: Allogeneic HSCT recipients with resolved HBV before HSCT are at prolonged risk for RS which makes prophylactic antiviral treatment unattractive. However, RS resulted in only one episode of symptomatic illness in this cohort. Furthermore, two recipients cleared HBsAg without antiviral therapy and among those who required treatment 40% cleared HBsAg durably.
Sarah P. Hammond - Grant/Research Support: Merck
Chinweike Ukomadu - Consulting: Gilead Sciences
The following people have nothing to disclose: Vincent T. Ho, Lindsey R. Baden, Francisco M. Marty