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Flares in chronic hepatitis B patients induced by the host or the virus? Relation to treatment response during Peg-interferon α-2b therapy
  1. H J Flink1,
  2. D Sprengers1,
  3. B E Hansen2,
  4. M van Zonneveld1,
  5. R A de Man1,
  6. S W Schalm1,
  7. H L A Janssen1,
  8. for the HBV 99-01 study group
  1. 1Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands
  2. 2Department of Epidemiology and Biostatistics, and Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands
  1. Correspondence to:
    Dr H L A Janssen
    Department of Gastroenterology and Hepatology, Erasmus Medical Centre, Dr. Molewaterplein 40, Room Ca 326, 3015 GD Rotterdam, the Netherlands;


Background and aims: Flares are a well known phenomenon during antiviral treatment for chronic hepatitis B. Little is known about the effect of flares on response. We investigated the timing and characteristics of flares, in relation to treatment response (hepatitis B e antigen loss).

Patients: A total of 266 patients, participating in a global randomised controlled study, were assigned to 52 weeks of 100 μg pegylated (Peg)-interferon α-2b weekly, combined with either daily lamivudine 100 mg or placebo.

Results: Sixty seven patients (25%) exhibited 75 flares, with 38 (51%) flares in the combination therapy and 37 (49%) in the monotherapy groups. Overall, 30% of patients with and 38% of patients without a flare responded to therapy (p = 0.25). In 24 patients (36%) the flare was followed by a decrease in hepatitis B virus (HBV) DNA (host induced flare). In 25 (38%) patients the flare was preceded by an increase in HBV DNA (virus induced flare). In 17 (26%) patients the flare did not meet one of these criteria (indeterminate flare). Of patients with host induced flare, 58% responded whereas only 20% of patients with virus induced flares responded (p = 0.008). Hepatitis B surface antigen loss (n = 8) was exclusively seen in patients experiencing a host induced flare. Multivariate logistic analysis showed that host induced flares was an independent predictor of response (p = 0.043).

Conclusion: Flares are not more common in responders than in non-responders to Peg-interferon α-2b therapy. Virus induced flares, which occur after an increase in HBV DNA level, and most probably are indicative for increased expression of viral antigens, did not lead to treatment response. In contrast, host induced flares which were followed by a HBV DNA decrease were highly associated with treatment response.

  • HBV, hepatitis B virus
  • HBeAg, hepatitis B e antigen
  • HBsAg, hepatitis B surface antigen
  • IFN, interferon
  • ALT, alanine aminotransferase
  • Peg, pegylated
  • CHB, chronic hepatitis B
  • ULN, upper limit of normal
  • hepatitis B virus
  • virus
  • chronic hepatitis B
  • Peg-interferon α-2b
  • hepatitis e antigen
  • hepatitis B surface antigen

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  • Published online first 29 May 2005

  • Other members of the HBV 99-01 study group are listed in the appendix.

  • Conflict of interest: None declared.