Response to pegintin HBeAg-ve : On-treatment kinetics of qHBsAg vary by genotype

[StephenCastlecrag]

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

    Maurizia R. Brunettoa, Corresponding author contact information, E-mail the corresponding author,
    Patrick Marcellinb,
    Beatrice Cherubinia,
    Cihan Yurdaydinc,
    Patrizia Farcid,
    Stephanos J. Hadziyannise,
    Vivien Rothef,
    Loredana Regepg,
    Ferruccio Boninoh

    a U.O. Epatologia–Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
    b Service d’Hépatologie and Centre de Recherches Biologiques Beaujon, University of Paris, Clichy, France
    c Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey
    d Department of Medical Sciences, University of Cagliari, Cagliari, Italy
    e Department of Medicine and Hepatology, Henry Dunant Hospital and Liver Research Unit of Athens University at Evgenidio Hospital Athens, Greece
    f IST GmbH, Mannheim, Germany
    g F. Hoffmann-La Roche, Basel, Switzerland
    h Cattedra di Gastroenterologia – Università Pisa, Italy

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.

[Jeff912000]

Nucs have a place.  It allows sequential treatment.  If you fail peg your can keep nucs.  Then try PEG again in a couple of years.  Not every one will repond to PEG.  Tenofovir can give the body a break from fighting and allow immune recovery.  

I also prefer more guns to fight hep b though.

[veteranB]

That is a good article. Very much somes up how they should be treating us.

Also shows how how worthless it is for us to take nucs. No antiviral can  claim these results that interferon  offers.

[Jeff912000]

This study is not informative enough.  There is really not enough information about genotype's HBSAg levels.  As Steff saids Genotype B needs <100iu/ml HBSAG and HEP B DNA <2000iu/ml to be true inactive carrier.  Other types like genotype D have high HBSAG to be carrier.  

[andrey19]

would be interesting to see hbs baselines and 12,24,48 weeks results to really see the kinetics. How long was the treatment with peg? 48 weeks?

[StephenCastlecrag]

The abstract is very brief.
"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. "

Maybe someone can provide access to the full paper or provide more information. It seems that Genotypes B and C require really low end-of-treatment qHBsAg to achieve long-term response?