Interferon‐α2a for chronic hepatitis B with e antigen or antibody: comparable antiviral effects on wild‐type virus and precore mutant

Abstract

Recombinant interferon-alpha 2a (IFN-alpha 2a) in a total dose of 702 MU was given to 31 patients: nine with wild-type hepatitis B virus (HBV) and hepatitis B e antigen (HBeAg) (A); four with HBeAg and a mixed infection with wild-type HB and precore mutants (B); 11 with antibody to HBeAg (HBeAb) and a mixed infection (C); and seven with HBeAb and precore mutants alone (D). HBV DNA was not cleared in any patient in groups A and B. By contrast, in patients with HBeAb, HBV DNA was ultimately lost in four patients in group C, as well as in 10 patients in group D. Thus, patients with HBeAb and infected with precore mutants alone (D) lost serum HBV DNA more often than those with HBeAg and wild-type HBV (A). Patients with low pretreatment levels of HBV DNA cleared virus more frequently, and the response of precore mutant to IFN was comparable with that of wild-type HBV in patients who had a mixed infection. Based on these results, precore mutants do respond to IFN, and therefore, IFN is indicated in patients with HBeAb, especially those with low serum HBV DNA levels.

Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action

“…Most studies have shown that approximately 30–40% of HBeAg-positive patients respond to IFN-α therapy. However, the rate to IFN-α therapy for HBeAg-negative patients is divergent: some studies reported that IFN-α response rate is up to 50% 44–46 , whereas others showed long-term IFN-α response rate is less than 10% 47–50 . Thus, we could not neglect the roles of other viral proteins, including HBsAg and HBp 23, 51, 52 , in the regulation of IFN-α actions.…”

Mutations of the core promoter and response to interferon treatment in chronic replicative hepatitis B

“…Most studies so far have shown poor long-term response rates of even less than 10% in HBeAg-negative hepatitis, [5][6][7][8][9] but some studies reported response rates up to 50%. [10][11][12] The highly divergent response rates to IFN therapy for HBeAg-negative hepatitis are difficult to explain. In HBeAg-positive hepatitis low HBV-DNA titers predict a favorable response to IFN.…”

“…However, the results are controversial. [10][11][12]18,19 Mutations in the polymerase gene play an important role for resistance to nucleoside analogues, but do not seem to have an effect on the outcome of IFN therapy. Whether variations of the core gene affect the response to IFN is under discussion.…”

“…[5][6][7][8][9] However, these data contrast with sustained response rates of 25% to 50% in HBeAg-negative patients. [10][11][12][13][14] Genetic viral factors have been poorly investigated for their effect on the outcome of IFN therapy. As yet, attention has focused on the precore region, the G1896A mutation in the precore region, and the core gene of HBV.…”

Adding interferon to lamivudine enhances the early virologic response and reversion of the precore mutation in difficult-to-treat HBV infection

“…The G1896A stop codon mutation in the precore region was detected by an enzyme-linked minisequence assay (Smitest HBV Pre-C ELMA, Roche Diagnostics). 9,10 When the mutation rate was 0%, the results were recorded as wild type; otherwise, they were mutantpositive. The A1762T and G1764A double mutations in the CP region were detected by an enzyme-linked specifi c probe assay (Smitest HBV core promoter mutation detection kit, Genome Science Laboratory, Tokyo, Japan).…”