HB sAg loss after peginterferon‐nucleotide combination treatment in chronic hepatitis B patients: 5 years of follow‐up

Summary Combining peginterferon‐alfa‐2a (peg IFN ) with a nucleotide analogue can result in higher rates of HB sAg loss than either therapy given alone. Here, we investigated the durability of the response to combination therapy in chronic hepatitis B ( CHB ) patients after 5 years of follow‐up. In the initial study, 92 CHB patients (44 HB eAg‐positive, 48 HB eAg‐negative) with HBV DNA >100 000 c/ mL (~20 000  IU / mL ) and active hepatitis were treated for 48 weeks with peg IFN 180 μg/week and 10 mg adefovir dipivoxil daily. For the long‐term follow‐up (LTFU) study, patients were followed up for 5 years after the end of treatment. At year 5, 70 (32 HB eAg‐positive, 38 HB eAg‐negative) patients remained in the study. At year 5, 19% (6/32) of HB eAg‐positive patients and 16% (6/38) of HB eAg‐negative patients lost HB sAg, and no HB sAg seroreversion was observed. The 5‐year cumulative Kaplan‐Meier estimate for HB sAg loss was 17.2% for HB eAg‐positive patients and 19.3% for HB eAg‐negative patients. Fourteen of sixteen patients who lost HB sAg at any time point during follow‐up developed anti‐ HB s antibodies (>10  IU /L). At year 5, in total 63% (20/32) of HB eAg‐positive and 71% (27/38) of HB eAg‐negative patients were retreated with nucleos(t)ide analogues during follow‐up. The cumulative Kaplan‐Meier estimate for retreatment was 60% of patients at year 5. At year 5 of follow‐up, 18% of CHB patients treated with peg IFN /nucleotide analogue combination therapy had durable HB sAg loss and 88% of these had developed anti‐ HB s antibodies.