Chronic hepatitis B (CHB) patients with advanced
fibrosis are often not considered for treatment with peginterferon (PEG-IFN) because IFN
therapy may precipitate immunological flares, potentially inducing hepatic decompensation. We investigated the efficacy and safety of treating
hepatitis B e antigen (
HBeAg)-positive CHB patients with 52 weeks of PEG-IFN-alpha-2b (100 microg weekly) alone or in combination with
lamivudine (100 mg daily). Seventy patients with advanced
fibrosis (Ishak
fibrosis score 4-6) and 169 patients without advanced
fibrosis, all with compensated
liver disease, participated in the study. Virologic response, defined as
HBeAg seroconversion and hepatitis B virus (HBV)
DNA < 10,000 copies/ml at week 78, occurred significantly more often in patients with advanced
fibrosis than in those without (25% versus 12%, respectively; P = 0.02). Also patients with
cirrhosis (n = 24) exhibited a virologic response more frequently than did patients without
cirrhosis (30% versus 14%, respectively; P = 0.02). Improvement in
liver fibrosis occurred more frequently in patients with advanced
fibrosis (66% versus 26%, P < 0.001). HBV genotype A was more prevalent among patients with advanced
fibrosis than among those without (57% versus 24%, P < 0.001). Most adverse events, including serious adverse events, were observed equally as frequently in patients with advanced
fibrosis and those without.
Fatigue,
anorexia, and
thrombocytopenia occurred more often in patients with advanced
fibrosis than in those without (P < 0.01). Necessary
dose reduction or discontinuation of
therapy was comparable for both patient groups (P = 0.92 and P = 0.47, respectively).
CONCLUSION: PEG-IFN is effective and safe for
HBeAg-positive patients with advanced
fibrosis. Because PEG-IFN
therapy results in a high rate of sustained off-
therapy response, patients with advanced
fibrosis or
cirrhosis but compensated
liver disease should not be excluded from PEG-IFN treatment.