Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy

Gastroenterology. 2006 Jul;131(1):59-68. doi: 10.1053/j.gastro.2006.04.015.


Background & aims: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / analysis
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Hepatitis B / complications
  • Hepatitis B / drug therapy*
  • Hepatitis B / virology
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Humans
  • Liver Failure, Acute / epidemiology
  • Liver Failure, Acute / etiology
  • Male
  • Middle Aged
  • Prevalence
  • Prognosis
  • Retrospective Studies
  • Risk Factors


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens