The long-term outcome of interferon-α treated and untreated patients with HBeAg-negative chronic hepatitis B
Introduction
The HBeAg-negative form of chronic hepatitis B represents a late phase in the natural course of chronic hepatitis B virus (HBV) infection, which follows HBeAg seroconversion [1]. The HBeAg-negative chronic hepatitis B is predominant in the Mediterranean basin and the Far East, and its frequency is rising worldwide [1]. In Greece, 90% of chronic hepatitis B patients are HBeAg-negative [1], all of them carrying HBV mutant strains with a precore stop codon [2].
Interferon-α (IFN) was the first-line therapy during the last decade [3], while lamivudine has recently been licensed for the treatment of chronic hepatitis B [4]. In HBeAg-positive chronic hepatitis B, IFN induces HBeAg clearance in about 33% [5], which is usually long lasting [6], [7] and is associated with reduction of HCC and improved survival [7], [8]. In HBeAg-negative chronic hepatitis B, however, the efficacy of IFN may be relatively poor with sustained remission rates limited to less than 25% [9], [10], [11], while its effect on the long-term outcome of the disease has not been clarified.
In our center, we have followed prospectively a large cohort of patients with HBeAg-negative chronic hepatitis B since the early 1980s. Thus, in the present study, we evaluated the effect of IFN therapy on the long-term outcome of this type of chronic hepatitis B.
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Patient population
All patients with HBeAg-negative chronic hepatitis B, who were seen at our center between January 1986 and December 1997 were considered for the study. Inclusion criteria were: HBsAg-positive and HBeAg-negative for ≥12 months, increased alanine aminotransferase (ALT) activity (>upper limit of normal (ULN)) in ≥2 separate monthly determinations, and histological findings of chronic hepatitis. Patients with coinfection with hepatitis delta virus (HDV), hepatitis C virus (HCV), or human
Patient characteristics – response to IFN
The baseline characteristics of IFN-treated and untreated patients are presented in Table 1. ALT levels were higher in the IFN-treated than untreated patients (P<10−3), but there was no difference in sex, age, IgM anti-HBc index, HBV DNA level, histological grade or stage or pre-existing cirrhosis, and duration of follow up. A total of 57 (27.3%) of the 209 treated patients eventually entered sustained biochemical remission after IFN treatment or retreatment (Table 1).
Twenty-seven patients
Discussion
Our study, which evaluated the largest published cohort of patients with HBeAg-negative chronic hepatitis B closely followed for up to 13.5 years, shows that presence of cirrhosis and old age are two major factors which are strongly and independently associated with decreased survival. Similar findings have also been reported by others in chronic hepatitis B irrespective of HBeAg status [14]. The 5-year cumulative survival in our cirrhotic patients was 76%, which is within the reported range of
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