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,
Stephanos J. Hadziyannise,
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
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.
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.
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.
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.
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?
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.
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.
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