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Pegint alfa-2a in eAg-ve CHB: On-treatment of HBsAg kinetics vary by genotype
Response to peginterferon alfa-2a (40KD) in HBeAg-negative CHB: On-treatment kinetics of HBsAg serum levels vary by HBV genotype

    Maurizia R. Brunettoemail address
    ,
    Patrick Marcellin
    ,
    Beatrice Cherubini
    ,
    Cihan Yurdaydin
    ,
    Patrizia Farci
    ,
    Stephanos J. Hadziyannis
    ,
    Vivien Rothe
    ,
    Loredana Regep
    ,
    Ferruccio Bonino

Received 15 April 2013; received in revised form 4 July 2013; accepted 6 July 2013. published online 22 July 2013.
Accepted Manuscript

  

Abstract
Background & aims

We investigated whether HBV genotype influences on-treatment HBsAg kinetics and/or the end-of-treatment HBsAg levels associated with long-term virological response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a ± lamivudine in the Phase III trial.
Methods

All patients (n = 230) who participated in long-term follow-up were included according to the availability of HBsAg levels measurements. Long-term virological response was defined as HBV DNA ⩽10,000 cp/mL (1786 IU/mL) at 5 years post-treatment. Genotype-specific end-of-treatment HBsAg levels associated with long-term virological response (identified by ROC analysis) were assessed in 199 patients with HBsAg measurements available at baseline and end-of-treatment. HBsAg kinetics according to genotype and long-term virological response were investigated in the 117 patients with additional samples available at weeks 12, 24 and 72.
Results

Baseline HBsAg levels were significantly higher for A than B, C and D genotypes (p<0.05). On-treatment HBsAg kinetics varied according to HBV genotype. The difference between responders and non-responders was greatest for genotype A from weeks 12 to 24; for genotypes B and D from baseline to week 12; there was no significant difference over any timeframe for genotype C. High positive predictive values for long-term virological response could be obtained by applying end-of-treatment genotype-specific cut-offs: 75%, 47%, 71% and 75% for genotypes A (<400 IU/mL), B (<50 IU/mL), C (<75 IU/mL) and D (<1000 IU/mL), respectively.
Conclusions

On-treatment HBsAg kinetics vary between HBV genotypes. Genotype-specific monitoring timeframes and end-of-treatment thresholds could ameliorate response-guided treatment of HBeAg-negative chronic hepatitis B.
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