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Blood, 1 April 2002, Vol. 99, No. 7, pp. 2324-2330
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
High hepatitis B virus (HBV) DNA viral load as the most important
risk factor for HBV reactivation in patients positive for HBV surface
antigen undergoing autologous hematopoietic cell transplantation
George K. K. Lau,
Yu-hung Leung,
Daniel Y. T. Fong,
Wing-yan Au,
Yok-lam Kwong,
Albert Lie,
Ji-lin Hou,
Yu-mei Wen,
Amin Nanj, and
Raymond Liang
From the Division of Gastroenterology and Hepatology
and the Division of Hematology, University Department of Medicine, the
Clinical Trials Centre, and the Department of Pathology, Queen Mary
Hospital, Institute of Molecular Technology for Drug Discovery and
Synthesis, Biology, Hong Kong Special Administrative Region; the
Department of Infectious Disease, Nanfang Hospital, Guangzhou; and the
Department of Molecular Virology, Fudan University, Shanghai, People's
Republic of China.
The risk factors for hepatitis due to hepatitis B virus (HBV)
reactivation in patients positive for hepatitis B surface antigen (HBsAg) treated with autologous hematopoietic cell transplantation (HCT) are unknown. We evaluated 137 consecutive patients (23 positive for HBsAg, 37 positive for hepatitis B surface antibody, and
77 negative for HBV) who underwent HCT. Serial serum ALT were measured before transplant and after transplant at 1 to 4 weekly intervals for
the first year and then at 2 to 12 weekly intervals thereafter. Before HCT, basic core promoter (T1762/A1764)
and precore (A1896) HBV variants were determined in
HBsAg-positive and HBV DNA-positive (by polymerase chain reaction
assay) patients by direct sequencing and serum HBV DNA quantitation
using the Digene Hybrid Capture II assay. Cox proportional hazards
analysis was used to assess the association between pretransplantation
HBV virologic and host factors and occurrence of hepatitis due to HBV
reactivation. After HCT, hepatitis due to HBV reactivation was more
common in HBsAg-positive patients than in HBsAg-negative patients
(hazard ratio, 33.3; 95% confidence interval [CI], 7.35-142.86;
P < .0001). HBsAg-positive patients with detectable
serum HBV DNA before HCT (on Digene assay) had a significantly higher
risk of hepatitis due to HBV reactivation than HBsAg-positive patients
with no detectable serum HBV DNA (adjusted hazard ratio, 9.35; 95% CI,
1.65-52.6; P = .012). Thus, we found that hepatitis due
to HBV reactivation is common in HBsAg-positive patients undergoing
autologous HCT. A high HBV DNA level (>105 copies/mL) was
the most important risk factor for HBV reactivation, and its lowering
by administration of nucleoside analogues before transplantation should
be considered.
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