Fulminant hepatitis B following bone marrow transplantation in an HBsAg-negative, HBsAb-positive recipient; reactivation of dormant virus during the immunosuppressive period

Abstract

Summary:It is widely accepted that seroconversion of HBsAg to HBsAb indicates clearance of hepatitis B virus. We describe a 50-year-old man with chronic myelocytic leukemia who developed lethal hepatitis B 22 months after allo-BMT. He had been negative for HBsAg and positive for HBsAb before BMT. Hepatitis B virus latently existing in the liver cells before BMT proliferated during the immunosuppressed period causing fatal hepatitis. Recipients with positive HBsAb should be considered to have the potential for active hepatitis B to emerge after BMT. Bone Marrow Transplantation (2000) 25, 105-108. Keywords: bone marrow transplantation; hepatitis B; HBsAg-negative The risk of hepatitis B caused in patients positive for hepatitis B surface antigen (HBsAg) by reactivation of the virus after bone marrow transplantation (BMT) has been well recognized. 1-3 However, hepatitis occurring in patients who had been positive for anti-hepatitis B surface antibody (HBsAb) before BMT is rarely reported. [4][5][6] We report here lethal hepatic failure that developed in an immunosuppressed patient after allo-BMT due to reactivation of latent hepatitis B virus (HBV) despite having HBsAb and no virus DNA detected in the serum before transplantation. MethodsEIA enzyme immunoassay kits AxSYM (Dinabot, Tokyo, Japan) were used for detection of HBsAg, HBsAb, anti-HBV core antibody (HBcAb), HBV e antigen (HBeAg) and anti-HBV e antibody (HBeAb). Serum HBV was measured by the branched DNA probe method using commercial Quantiplex HBV-DNA (Chiron, Emeryville, CA, USA). All procedures were performed according to the manufacturer's recommendations. Polymerase chain reaction (PCR) assays were performed as described previously. 7 Case reportA 50-year-old man consulted our hospital in April 1995 for leukocytosis that had been found on a regular checkup at his company and which was accompanied by abdominal fullness. He had splenomegaly 16 cm below the left costal margin and the peripheral blood showed a leukocytosis with basophilia. Bone marrow aspiration and biopsy revealed a hypercellular marrow with a very low G/E ratio and an increased percentage of blast cells, although the value remained under 30%, and myelofibrosis. The karyotype of all bone marrow cells examined was 46XY, t(9;22) (q34;q11). BCR-ABL fusion mRNA was also detected by the PCR method. He was diagnosed as having a chronic myelocytic leukemia in accelerated phase and was treated with hydroxyurea and interferon-␣. Because stable hematological remission was not obtained and his disease was considered to be very close to blast crisis, he underwent unrelated bone marrow transplantation from an HLA one locus mismatched 43-year-old female donor in April 1996. He was given buslfan 3.6 mg/kg over 4 days, cytarabin 50 mg/kg over 3 days, and cyclophosphamide 60 mg/kg over 3 days without total body irradiation as conditioning therapy. FK506 and short-term methotrexate were used for prophylaxis of acute GVHD. Engraftment was confirmed on day 13 by X-chromosomal examination (FISH). The level of...

Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation

“…21 HBV-associated liver disease after allo-HSCT is often temporary and not serious, but fatal liver damage has been reported in some cases. 16,18 In the three patients with reverse seroconversion reported herein, there was mild hepatitis in only one patient, followed by spontaneous clearance of HBsAg. The other two patients had no biochemical signs of liver damage but became chronic carriers with high-level HBV viraemia.…”

Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy

“…This has been postulated to be due to a delay in antiviral administration at a time when severe hepatic impairment with massive hepatic damage had already occurred. 18,[48][49]79,103 Thus, it is possible that only with prompt administration of the antiviral (i.e., the first instance in which HBV DNA first starts to rise and before severe irreversible hepatic damage) will it be effective. However, the potential intense monitoring modality may not be cost-effective and may be difficult to conduct in clinics that lack adequate laboratory support.…”

“…[39][40][41][42][43][44][45][46][47][48][49][50] Based on reported series, 47,[51][52][53][54] the frequency of seroreversion ranges between 14% and 50% (Table 1A). The wide range reported could be explained by risk estimation based on small series, missed cases of seroreversion due to absence of symptoms, and variable duration of posttransplant follow-up.…”

“…among a total of 39 patients in the literature. [48][49] The suggested factors for reversion hepatitis include the use of corticosteroids, 50,54 lack of anti-HBs in donor, 50,51,54 and graft-versus-host disease. [52][53] For patients receiving autologous HSCT, Lau et al 53 reported that only 1 of 37 anti-HBs-positive patients (23 of whom were also anti-HBc-positive) developed viral reactivation after transplant, a finding that was associated with nonfulminant hepatitis.…”

Histological improvement with lamivudine therapy for de novo hepatitis B occurring in an anti-HBs-positive child after bone marrow transplantation

“…[1][2][3]6 In our case, liver biopsies (performed 6 months apart) demonstrated chronic hepatitis progressing to extensive fibrosis, indicating a guarded prognosis.…”