LAUSR

Background We aimed to identify HBc amino acid differences between subgroups of chronic hepatitis B (CHB) patients. Methods Deep sequencing of HBc was performed in samples of 89 CHB patients (42 HBeAg positive, 47 HBeAg negative). Amino acid types were compared using Sequence Harmony to identify subgroup specific sites between HBeAg‐positive and ‐negative patients, and between patients with combined response and non‐response to peginterferon/adefovir combination therapy. Results We identified 54 positions in HBc where the frequency of appearing amino acids was significantly different between HBeAg‐positive and ‐negative patients. In HBeAg negative patients, 22 positions in HBc were identified which differed between patients with treatment response and those with non‐response. The fraction non‐consensus sequence on selected positions was significantly higher in HBeAg‐negative patients, and was negatively correlated with HBV DNA and HBsAg levels. Conclusions Sequence Harmony identified a number of amino acid changes associated with HBeAg‐status and response to peginterferon/adefovir combination therapy. HighlightsThe HBV core protein is a promising target for the design of new antiviral treatments.We identified amino acid changes in HBV core protein associated with HBeAg status and response to antiviral treatment.HBc Amino acid variation was significantly higher in HBeAg negative patients, and negatively correlated with HBV DNA levels.