A number of different subgroup-specific sites have been observed between individuals with chronic hepatitis B who are HBeAg positive or negative, as well as between individuals who are responsive and unresponsive to peginterferon/adefovir combination therapy. This study was recently published in Antiviral Research.

This study included 89 individuals with chronic hepatitis B, 42 of whom were HBeAg positive and 47 of whom were HBeAg negative. Sequence Harmony identified 54 sites with scores below 0.960, indicating areas where the 2 study groups diverge in amino acid composition (Z-scores <-0.8; ≥50 reads).

Additionally, Sequence Harmony showed 22 sites where HBc amino acids differed between HBeAg negative with and without response to treatment (Z-scores <-0.8; ≥50 reads). HBeAg-negative participants showed significantly higher median amino acid variation in certain sites than other groups.

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This trend showed a negative correlation with levels of HBsAg and HBV DNA. Both HBV genotype and the presence of BCP mutations were revealed via multivariable regression to be independent of the association between HBeAg negative status and increased amino acid non-consensus.

Initially, 92 patients with chronic hepatitis B received 48 weeks of treatment with weekly subcutaneous peginterferon alfa-2a 180 μg and daily adefovir dipivoxil 10 mg. Of these, 84 completed both treatment and 2 years of follow-up.

At week 72 of post-treatment follow-up, participants were assessed for achievement of combined response, which included HBV DNA levels ≤2000 IL/mL, negative HBeAg status, and sustained normal levels of alanine aminotransferase. Sequence Harmony was used to identify common sites between the subgroups of HBeAg status and between those with response and non-response to therapy.

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The study researchers conclude that “Sequence Harmony identified a number of amino acid changes associated with HBeAg-status and response to peginterferon/adefovir combination therapy.”

Disclosures: This study was funded by Roche the Netherlands.


van der Ree MH, Jansen L, Welkers MRA, Reesink HW, Feenstra KA, Kootstra NA. Deep sequencing identifies hepatitis B virus core protein signatures in chronic hepatitis B patients [published online August 16, 2018]. Antiviral Res. doi: 10.1016/j.antiviral.2018.08.009