Detection of reactivation and genetic mutations of the hepatitis B virus in patients with chronic hepatitis B infections receiving hematopoietic stem cell transplantation.
BACKGROUND
This study elucidates the profiles for hepatitis B virus (HBV) reactivation and genetic mutation of the core promoter and precore regions for HBV-carriers receiving hematopoietic stem cell transplantation (HSCT).


METHODS
Sera from 20 HSCT patients diagnosed with hematological diseases, 13 donors and 36 healthy HBV-carriers, were collected regularly for analysis. The hepatic biochemistry profiles, serological HBV markers, and HBV-DNA titers were checked regularly, and primer-amplification of the HBV core promoter or precore region and sequencing were performed once the mutations were identified.


RESULTS
Deteriorated liver function was demonstrated for 13 of 20 post-HSCT patients, compared with none of the 36 controls (P<0.01). The HBV-DNA was detected more frequently for post-HSCT subjects than for controls (P=0.001). Incidence of the HBV precore nucleotide 1896 G-to-A mutation was significantly higher for HSCT patients (P=0.004), and a significant association was demonstrated for carriage of core promoter or precore mutations and the development of hepatitis (P=0.015). Different HBV genotypes were revealed in post-HSCT patients and the respective donors.


CONCLUSIONS
Intensive chemotherapy and immunosuppression may cause HBV reactivation in HBV carriers receiving HSCT, and more frequent core promoter or precore mutations could be detected in HBV carriers receiving HSCT than healthy HBV carriers, with the chemotherapy/immunosuppression-induced immunocompromise possibly contributing to this effect. Donor HBV genotype did not interfere with that of the recipient after HSCT. Core promoter or precore region mutations were associated with a higher incidence of liver dysfunction than wild-type HBV carriers in the HSCT patients.
Chen
Po-Min
PM
Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital; Department of Medicine, Taipei, Republic of China.
Yao
Nai-Shun
NS
Wu
Ching-Mei
CM
Yang
Muh-Hwa
MH
Lin
Yu-Chen
YC
Hsiao
Liang-Tsai
LT
Yen
Chueh-Chuan
CC
Wang
Wei-Shu
WS
Fan
Frank S
FS
Chiou
Tzeon-Jye
TJ
Liu
Jin-Hwang
JH
Lo
Szecheng J
SJ
D000328:Adult; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation; D006515:Hepatitis B virus / Q000235:genetics / Q000254:growth & development*; D019694:Hepatitis B, Chronic / Q000628:therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D014775:Virus Activation
D004279:DNA, Viral