Fulminant hepatitis after allogenic bone marrow transplantation caused by reactivation of hepatitis B virus with gene mutations in the core promotor region.
Under immunosuppressive conditions after hematopoietic stem cell transplantation (HSCT), even if hepatitis B virus (HBV) antigen is negative but hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb) is presented, HBV reactivates and sometimes causes fulminant hepatitis. However, it remains unclear which patients will develop fulminant hepatitis, or whether fulminant hepatitis is caused by host-related factors or by virus-related factors. A 30-yr-old man with a history of aplastic anemia since 3 yr of age underwent allogenic BMT, when HBsAb and HBcAb were positive but HBs antigen (HBsAg) was negative. The donor was negative for HBsAg, HBsAb and HBcAb. After transplantation, the patient was complicated by acute graft-vs.-host disease (GVHD), cytomegalovirus infection, intestinal thrombotic microangiopathy and aspergillus colitis. Chronic GVHD was well controlled by FK506 and prednisolone. Twenty months after transplantation, the patient was admitted with general fatigue and liver dysfunction and was found to be positive for HBsAg and HBeAg. His serum HBV-DNA level was >8.8 log of the genome equivalent (LGE)/mL. Therefore, he was diagnosed as having hepatitis B caused by HBV reactivation and 100 mg/d lamivudine treatment was started. However, jaundice and hepatic failure deteriorated and became fatal. On analysis of the HBV-DNA, two adjacent gene mutations in the core promoter region (T1762/A1764) were detected. Increased replication of the mutated HBV might have caused HBV reactivation which progressed to fulminant hepatitis.
Kitano
Kiyoshi
K
Department of Internal Medicine, Matsumoto National Hospital, Matsumoto, Japan. kiyoshikitano@mac.com
Kobayashi
Hikaru
H
Hanamura
Mayu
M
Furuta
Kiyoshi
K
Ueno
Mayumi
M
Rokuhara
Akinori
A
Tanaka
Eiji
E
Umemura
Takeji
T
Kiyosawa
Kendo
K
D000208:Acute Disease; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D005814:Genes, Viral; D006509:Hepatitis B / Q000209:etiology* / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D009154:Mutation; D011401:Promoter Regions, Genetic; D014184:Transplantation, Homologous; D014775:Virus Activation / Q000235:genetics
D006512:Hepatitis B Core Antigens