Pretreatment viral DNA stratifies mortality risk in patients receiving antiviral therapy for severe acute exacerbation of chronic hepatitis B

Antivir Ther. 2013;18(2):221-8. doi: 10.3851/IMP2435. Epub 2012 Nov 6.

Abstract

Background: Prognostic factors have not been elucidated for severe acute exacerbation of chronic hepatitis B treated with antiviral therapy. This study aimed to explore the role of baseline viral load in predicting mortality.

Methods: This retrospective cohort study screened consecutive chronic hepatitis B patients (n=84) receiving antiviral therapy for severe acute exacerbation, defined as abrupt elevation of serum alanine aminotransferase >10× the upper limit of normal along with hyperbilirubinaemia. Survival pattern was evaluated by the Kaplan-Meier method and predictors for mortality determined by the Cox regression analysis.

Results: A total of 66 patients were eligible and followed-up for a median of 23 months (range 0.1-75.0). Overall, 20 (30.3%) patients died during the study period, with the vast majority (n=17) succumbing rapidly within 3 months of severe acute exacerbation. The multivariate Cox model revealed that mortality was associated with baseline viral DNA level (HR 1.49 per log copies/ml, 95% CI 1.13, 1.96), international normalized ratio for prothrombin time (HR 2.68 per unit, 95% CI 1.81, 3.98), platelet count (HR 0.87 per 10(4) cells/μl, 95% CI 0.78, 0.98) and age (HR 1.10 per year, 95% CI 1.05, 1.15). A significant interaction existed between viral DNA and prolonged prothrombin time (P=0.005). Stratified analyses further demonstrated that pronounced coagulopathy heralded death irrespective of viral load, whereas serum level of viral DNA stratified mortality risk among those without marked coagulopathy.

Conclusions: Pretreatment viral DNA level stratifies risk of death in patients with severe acute exacerbation of chronic hepatitis B before the manifestation of overt liver failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use*
  • Disease Progression
  • Female
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / mortality
  • Hepatitis B, Chronic / virology*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Treatment Outcome
  • Viral Load*
  • Young Adult

Substances

  • Antiviral Agents