N Engl J Med 1996 May 30;334(22):1422-7

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

Niederau C, Heintges T, Lange S, Goldmann G, Niederau CM, Mohr L, Haussinger D
Department of Medicine, Heinrich Heine University Dusseldorf, Germany.

Abstract
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 outcome