Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy.
OBJECTIVE
De novo hepatitis B virus (HBV)-related hepatitis after chemotherapy results in high morbidity and mortality. We evaluate the clinical course of de novo HBV-related hepatitis after chemotherapy.


METHODS
Two hundred forty-four consecutive hepatitis B surface antigen (HBsAg)-negative lymphoma patients treated with chemotherapy were followed up for a median of 12.4 (range, 0.1-65.0) months. Serially collected serum samples were analyzed for hepatitis, serum HBV DNA, and HBsAg seroreversion.


RESULTS
Eight of the 244 patients (3.3%) developed de novo HBV-related hepatitis. A 100-fold increase in serum HBV DNA preceded de novo HBV-related hepatitis by a median of 18.5 (range, 12-28) weeks. All 8 patients had normal serum alanine aminotransaminase level when the 100-fold increase in serum HBV DNA occurred. Patients with de novo HBV-related hepatitis were more likely to have occult HBV infection before chemotherapy. Direct sequencing results showed that these 8 patients had de novo HBV-related hepatitis from reactivation of occult HBV infection. Three of the 8 patients with de novo HBV-related hepatitis compared with 6 of the 236 patients without de novo HBV-related hepatitis developed fulminant hepatic failure (37.5% vs 2.5%, respectively, P < .001). On multivariate Cox analysis, de novo HBV-related hepatitis was independently associated with a higher risk of fulminant hepatic failure (relative risk, 29.854; 95% confidence interval: 4.844-183.980; P < .001).


CONCLUSIONS
Close surveillance for a 100-fold increase in HBV DNA is recommended for HBsAg-negative patients treated with chemotherapy so that early commencement of antiviral therapy can be initiated before the occurrence of de novo HBV-related hepatitis.
Hui
Chee-Kin
CK
Centre For The Study of Liver Diseases, The University of Hong Kong, Hong Kong SAR, China. ckhui23@gmail.com
Cheung
Winnie W W
WW
Zhang
Hai-Ying
HY
Au
Wing-Yan
WY
Yueng
Yui-Hung
YH
Leung
Anskar Y H
AY
Leung
Nancy
N
Luk
John M
JM
Lie
Albert K W
AK
Kwong
Yok-Lam
YL
Liang
Raymond
R
Lau
George K K
GK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D017114:Liver Failure, Acute / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens