Reactivation of Hepatitis B Virus in Hematopoietic Stem Cell Transplant Recipients in Japan: Efficacy of Nucleos(t)ide Analogues for Prevention and Treatment

Abstract

We retrospectively reviewed 413 recipients with hematologic malignancies who underwent hematopoietic stem cell transplantation (HSCT) between June 1986 and March 2013. Recipients with antibody to hepatitis B core antigen (anti-HBc) and/or to hepatitis B surface antigen (anti-HBs) were regarded as experiencing previous hepatitis B virus (HBV) infection. Clinical data of these recipients were reviewed from medical records. We defined ≥1 log IU/mL increase in serum HBV DNA from nadir as HBV reactivation in hepatitis B surface antigen (HBsAg)-positive recipients, and also defined ≥1 log IU/mL increase or re-appearance of HBV DNA and/or HBsAg as HBV reactivation in HBsAg-negative recipients. In 5 HBsAg-positive recipients, 2 recipients initially not administered with nucleos(t)ide analogues (NUCs) experienced HBV reactivation, but finally all 5 were successfully controlled with NUCs. HBV reactivation was observed in 11 (2.7%) of 408 HBsAg-negative recipients; 8 of these were treated with NUCs, and fortunately none developed acute liver failure. In 5 (6.0%) of 83 anti-HBc and/or anti-HBs-positive recipients, HBV reactivation occurred. None of 157 (0%) recipients without HBsAg, anti-HBs or anti-HBc experienced HBV reactivation. In HSCT recipients, HBV reactivation is a common event in HBsAg-positive recipients, or in HBsAg-negative recipients with anti-HBc and/or anti-HBs. Further attention should be paid to HSCT recipients with previous exposure to HBV.

Hepatitis B virus reactivation in HBsAg-negative patients is associated with emergence of viral strains with mutated HBsAg and reverse transcriptase

“…Substitution at this position has been shown to confer resistance of HBV strains to lamivudine as well as adefovir (Gerolami et al, 2006). Although most published studies used lamivudine and lamivudine is still proposed in the preemptive or prophylactic treatment of HBV reactivation following chemotherapy (European Association For The Study Of The Liver, 2012), the present data add further evidence that the use of drugs with a high genetic barrier for resistance (tenofovir and entecavir) should be favored in the clinical context of HBV reactivation (Seto et al, 2014;Salpini et al, 2015;Colson et al, 2008;Nakamoto et al, 2014;Kim et al, 2012;Li et al, 2011). In this view, it is noteworthy that in the present work, all deaths occurred between 2002 and 2006 (i.e.…”

Hepatitis B reactivation in occult viral carriers undergoing hematopoietic stem cell transplantation: A prospective study

“…HBV reactivation has been reported in HBsAg‐positive carriers undergoing allogeneic or autologous hematopoietic stem cell transplantation (HSCT), but its risk in HBsAg‐negative, anti‐HBc–positive patients has not been clearly defined. The frequency of HBV reactivation in HBsAg‐negative, anti‐HBc–positive patients after HSCT might range from 2.6% to 42.9% . These variable frequencies were related to the lack of regular monitoring after HSCT or using HBsAg seroreversion, a relatively late clinical event, to define HBV reactivation .…”

Vacunación de pacientes adultos receptores de trasplante de células madre hematopoyéticas: Perspectiva de Costa Rica

“…La reactivación de la infección latente por hepatitis B, conocida como seroconversión reversa, es una complicación seria posterior al trasplante alogénico de células madre 65 , pero que también se ha descrito en trasplante autólogo 66 . En un estudio con 413 pacientes con HBsAg (+), que recibieron trasplante hematopoyético, la reactivación viral fue un evento común después del procedimiento 67 . Disrupciones en el balance entre la replicación viral y el control inmune contra el virus después del trasplante, pueden contribuir a la reactivación del virus, provocando inclusive falla hepática fulminante [68][69][70] .…”

“…Por estas razones, se recomienda inmunizar a todos los pacientes que exhiban positividad para HBsAg o anti-HBc, ya que la vacunación contra HBV puede reducir el riesgo de desarrollar dicha entidad 64,72,73 . Así mismo, la administración profiláctica de antivirales en el período post-trasplante puede ser necesaria para evitar la reactivación 67,74,75 . Por otra parte, si el donador de células hematopoyéticas es portador de hepatitis B, se recomienda llevar a indetectable la carga viral del donador por medio de terapia antivírica antes de la donación.…”