Hepatitis B surface antigen reduction by switching from long‐term nucleoside/nucleotide analogue administration to pegylated interferon

<jats:title>Summary</jats:title><jats:p>Hepatitis B surface antigen (<jats:styled-content style="fixed-case">HB</jats:styled-content>sAg) reduction during nucleoside/nucleotide analogue (<jats:styled-content style="fixed-case">NA</jats:styled-content>) therapy is slow and an alternative strategy for patients receiving ongoing <jats:styled-content style="fixed-case">NA</jats:styled-content> to facilitate <jats:styled-content style="fixed-case">HB</jats:styled-content>sAg reduction is required. We investigated whether switching to pegylated interferon (<jats:styled-content style="fixed-case">PEG</jats:styled-content>‐<jats:styled-content style="fixed-case">IFN</jats:styled-content>) after long‐term <jats:styled-content style="fixed-case">NA</jats:styled-content> administration enhances <jats:styled-content style="fixed-case">HB</jats:styled-content>sAg reduction. Forty‐nine patients who switched from long‐term <jats:styled-content style="fixed-case">NA</jats:styled-content> to 48 weeks of <jats:styled-content style="fixed-case">PEG</jats:styled-content>‐<jats:styled-content style="fixed-case">IFN</jats:styled-content> alfa‐2a were studied. The mean duration of previous <jats:styled-content style="fixed-case">NA</jats:styled-content> was 48 months (sequential group). A total of 147 patients who continued <jats:styled-content style="fixed-case">NA</jats:styled-content> and matched for baseline characteristics were analysed for comparison (<jats:styled-content style="fixed-case">NA</jats:styled-content> continuation group). The treatment response was defined as <jats:styled-content style="fixed-case">HB</jats:styled-content>sAg reduction ≥1.0 log<jats:styled-content style="fixed-case">IU</jats:styled-content>/mL at the end of <jats:styled-content style="fixed-case">PEG</jats:styled-content>‐<jats:styled-content style="fixed-case">IFN</jats:styled-content>. <jats:styled-content style="fixed-case">HB</jats:styled-content>sAg reduction at week 48 was 0.81±1.1 log<jats:styled-content style="fixed-case">IU</jats:styled-content>/mL in the sequential group, which was significantly higher than that in the <jats:styled-content style="fixed-case">NA</jats:styled-content> continuation group (0.11±0.3 log<jats:styled-content style="fixed-case">IU</jats:styled-content>/mL, <jats:italic>P</jats:italic> < .001). The treatment response was achieved in 29% and 2% of the sequential group and <jats:styled-content style="fixed-case">NA</jats:styled-content> continuation group (<jats:italic>P</jats:italic> < .001), and the odds ratio of sequential therapy for the treatment response was 19 compared with the <jats:styled-content style="fixed-case">NA</jats:styled-content> continuation (<jats:italic>P</jats:italic> < .001). In patients tested positive for hepatitis B e antigen (<jats:styled-content style="fixed-case">HB</jats:styled-content>eAg), <jats:styled-content style="fixed-case">HB</jats:styled-content>eAg seroconversion was higher in the sequential group (44% vs 8%, <jats:italic>P</jats:italic> < .001). In <jats:styled-content style="fixed-case">HB</jats:styled-content>eAg‐negative patients, only patients in the sequential group achieved <jats:styled-content style="fixed-case">HB</jats:styled-content>sAg loss. No patient needed to resume <jats:styled-content style="fixed-case">NA</jats:styled-content> administration because of <jats:styled-content style="fixed-case">HBV DNA</jats:styled-content> increase accompanied by alanine aminotransferase flares. In summary, sequential therapy with <jats:styled-content style="fixed-case">PEG</jats:styled-content>‐<jats:styled-content style="fixed-case">IFN</jats:styled-content> after long‐term <jats:styled-content style="fixed-case">NA</jats:styled-content> enhances the reduction of <jats:styled-content style="fixed-case">HB</jats:styled-content>sAg and may represent a treatment option to promote <jats:styled-content style="fixed-case">HB</jats:styled-content>sAg loss.</jats:p>