Pegylated interferon alfa-2a (PEG-IFN) may induce sustained virological response (SVR) inS ubstantial advances have been made in the treatment of chronic hepatitis B (CHB) in the past decade. Several nucleos(t)ide analogues are currently approved for the treatment of hepatitis B virus (HBV) infection with a high efficacy in suppressing HBV replication. However, a long duration of treatment is needed to maintain viral suppression, and the major question of whether oral therapy can ever be stopped remains unanswered. 1 In parallel with analogues, the American Association for the Study of Liver Diseases practice guidelines have advocated pegylated interferon alfa-2a (PEG-IFN) as a potential first-line therapy in hepatitis B e antigen (HBeAg)-negative patients. 2 The advantages of PEG-IFN therapy include a limited treatment course, a high rate of HBeAg seroconversion (in HBeAg-positive patients), a 20% to 30% rate of sustained virological response (SVR), the potential for hepatitis B surface antigen (HBsAg) loss or seroconversion, and a lack of resistance development. 3 Nonetheless, the use of PEG-IFN currently accounts for

In chronic hepatitis B (CHB), the persistence of hepatitis B surface antigen (HBs Ag) is sometimes associated with antibodies (Ab) to HBs (anti-HBs). To assess the hypothesis of the selection of HBs Ag immune escape variants in CHB patients, the variability of the HBV S gene was determined for patients persistently carrying both HBs Ag and anti-HBs antibodies and patients solely positive for HBs Ag. We selected 14 patients who presented both markers (group I) in several consecutive samples and 12 patients positive for HBs Ag only (group II). The HBs Ag-encoding gene was amplified and cloned, and at least 15 clones per patient were sequenced and analyzed. The number of residue changes within the S protein was 2.7 times more frequent for group I than for group II patients and occurred mostly in the "a" determinant of the major hydrophilic region (MHR), with 9.52 versus 2.43 changes per 100 residues (P ‫؍‬ 0.009), respectively. Ten patients (71%) from group I, but only three (25%) from group II, presented at least two residue changes in the MHR. The most frequent changes in group I patients were located at positions s145, s129, s126, s144, and s123, as described for immune escape variants. In CHB patients, the coexistence of HBs Ag and anti-HBs Ab is associated with an increase of "a" determinant variability, suggesting a selection of HBV immune escape mutants during chronic carriage. The consequences of this selection process with regard to vaccine efficacy, diagnosis, and clinical evolution remain partially unknown.