Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B

N Engl J Med. 1996 May 30;334(22):1422-7. doi: 10.1056/NEJM199605303342202.


Background: In patients with chronic hepatitis B, treatment with interferon alfa and the consequent loss of hepatitis B e antigen (HBeAg) from the blood leads to a reduction in inflammatory activity, but the clinical benefits of this treatment have not been established. We evaluated whether HBeAg seroconversion induced by interferon alfa improves clinical outcome.

Methods: We studied prospectively a cohort of 103 patients treated with interferon alfa for chronic hepatitis B; the mean (+/- SD) follow-up was 50.0 +/- 19.8 months. Fifty-three untreated patients served as controls.

Results: After treatment with interferon alfa, 53 of 103 patients no longer had detectable HBeAg or hepatitis B virus DNA, although only 10 patients became seronegative for hepatitis B surface antigen (HBsAg) (Kaplan-Meier estimates of cumulative clearance rates at five years, 56.0 percent for HBeAg and 11.6 percent for HBsAg). Of the 53 untreated patients, only 7 spontaneously eliminated HBeAg (28.1 percent at five years), and all remained positive for HBsAg (p < 0.001 for the Comparison with the treated patients, by the proportional-hazards model). During follow-up, 6 of the 103 treated patients died of liver failure, and 2 needed liver transplantation, all 8 were persistently positive for HBeAg. In another eight treated patients, complications of cirrhosis developed; all but one of these patients remained positive for HBeAg. Overall survival and survival without clinical complications were significantly longer in patients who were seronegative for HBeAg after therapy with interferon alfa than in those who remained seropositive (P = 0.004 and P = 0.018, respectively). In a regression analysis, clearance of HBeAg was the strongest predictor of survival. Of the 53 untreated patients, 13 had severe complications (including 4 deaths and 1 need for liver transplantation); all 13 continued to be HBeAg-positive.

Conclusions: In patients with chronic hepatitis B infection, the clearance of HBeAg after treatment with interferon alfa is associated with improved clinical outcomes.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • Hepatitis B / blood
  • Hepatitis B / mortality
  • Hepatitis B / therapy*
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / isolation & purification
  • Hepatitis, Chronic / blood
  • Hepatitis, Chronic / mortality
  • Hepatitis, Chronic / therapy*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Prospective Studies
  • Recombinant Proteins
  • Survival Analysis
  • Treatment Outcome


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins