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

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.