title: Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy.
abstract: 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.
authors.affiliation: Centre For The Study of Liver Diseases, The University of Hong Kong, Hong Kong SAR, China. ckhui23@gmail.com
authors.forename: Chee-Kin
authors.initials: CK
authors.lastname: Hui
authors.forename: Winnie W W
authors.initials: WW
authors.lastname: Cheung
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zhang
authors.forename: Wing-Yan
authors.initials: WY
authors.lastname: Au
authors.forename: Yui-Hung
authors.initials: YH
authors.lastname: Yueng
authors.forename: Anskar Y H
authors.initials: AY
authors.lastname: Leung
authors.forename: Nancy
authors.initials: N
authors.lastname: Leung
authors.forename: John M
authors.initials: JM
authors.lastname: Luk
authors.forename: Albert K W
authors.initials: AK
authors.lastname: Lie
authors.forename: Yok-Lam
authors.initials: YL
authors.lastname: Kwong
authors.forename: Raymond
authors.initials: R
authors.lastname: Liang
authors.forename: George K K
authors.initials: GK
authors.lastname: Lau
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens