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60th Annual Meeting of the American Association for the Study of Liver Diseases
Boston, MA, Hynes Convention Center
October 30-November 3, 2009
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HBsAg Decline in HBeAg-Negative Patients Treated With Peginterferon Alfa-2a is Associated With Sustained Response up to 5 Years Post-Treatment: Patients with Continuous HBsAg Decline Starting Before Week 24 Achieve Highest Rates of Response
  Reported by Jules Levin
60th Annual Meeting of the American Association for the Study of Liver Diseases 30 October - 3 November 2009, Boston, USA
Brunetto MR,1 Marcellin P,2 Bonino F,3 Kapprell H-P,4 Messinger D,5 Batrla R6 1 UO Epatologia, Azienda Ospedaliero Pisana, Pisa, Italy; 2 Service d'Hepatologie and Centre de Recherches Biologiques Beaujon, University of Paris, Clichy, France; 3 Direzione Scientifica, Foundation IRCCS, Policlinico di Milano and University of Pisa, Pisa, Italy; 4 Abbott GmbH & Co, Wiesbaden, Germany; 5 IST GmbH , Mannheim, Germany; 6Hoffman-La Roche Ltd, Basel, Switzerland
Author Conclusions
On-treatment HBsAg decline is associated with sustained post-treatment response to PEGASYS with highest response rates in those with continuous decline in HBsAg levels
Further studies are warranted to determine if patients with a late HBsAg decline may benefit from extending PEGASYS treatment beyond the standard 48-week course
Author Summary
The pattern of HBsAg decline during peginterferon alfa-2a ± lamivudine treatment is reflected by post-treatment response rates
Patients with a continuous HBsAg decline from baseline to the end of therapy had the highest rates of sustained immune control and HBsAg clearance
Our results are based on a standard 48-week course of PEGASYS. Interestingly, we noted that patients who experienced a late decline in HBsAg had a good rate of achieving sustained immune control - and we may speculate that the rate of sustained immune control could be higher if these patients received extended treatment
Retrospective analysis of a phase 3 study of peginterferon alfa-2a ± lamivudine in patients with HBeAg-negative chronic hepatitis B (CHB) has shown that this treatment regimen results in HBsAg decline1,2
We have shown previously that on-treatment HBsAg decline is associated with sustained post-treatment response (or sustained immune control) up to 5 years post-treatment in HBeAg-negative patients2,3
Additional independent studies of peginterferon alfa-2a have highlighted that quantification of HBsAg levels during treatment may help to identify patients most likely to achieve sustained response4,5
As not all patients achieve a sustained response with the standard duration of interferon-based therapy, a current focus of research is to identify ways of increasing the post-treatment response rate to peginterferon alfa-2a. Early studies have shown that additional benefits can be obtained by HBeAg-negative patients when the duration of conventional interferon therapy is extended beyond 1 year.6,7 A pilot study highlighted that the advantages of extension therapy initially observed with conventional interferon were also apparent following treatment with peginterferon alfa-2a.8 It is possible that the pattern of HBsAg decline during treatment may help identify patients for whom extended therapy should be considered
In the current analysis, we investigate the pattern of HBsAg decline in patients with HBeAg-negative CHB treated with peginterferon alfa-2a ± lamivudine to determine any potential influence on the achievement of sustained posttreatment response
HBeAg-negative patients had received peginterferon alfa-2a (PEGASYS, 180 µg/week) ± lamivudine (100 mg/day) for 48 weeks as part of the phase 3 study described previously.9 Patients were followed up for 24 weeks (6 months) as part of the initial study
A total of 230 peginterferon alfa-2a ± lamivudine-treated patients entered a longterm follow-up study where they were followed for up to 5 years post-treatment
Quantitative serum HBsAg levels were measured retrospectively at baseline and at weeks 12, 24 and 48 weeks of treatment and 6 months post-treatment (week 72) using the Abbott Architect HBsAg assay in available sera
· Only patients with HBsAg values available at all time points (baseline and weeks 12, 24, 48 and 72) were included in the current analysis: N=155 at 6 months post-treatment and N=120 at 5 years post-treatment
Patients were divided according to on-treatment HBsAg decline (defined as a 10% decrease from baseline) into one of four groups (Table 1)
The proportion of patients achieving sustained immune control (defined as HBV DNA ≥10,000 copies/mL) at 6 months and 5 years post-treatment and the proportion of patients achieving HBsAg clearance 5 years post-treatment were determined according to on-treatment decline


The majority of patients with data available had a continuous decline in HBsAg level from baseline (Figure 1)
Figure 1. Proportion of patients in either the 6 month or 5 year analysis populations in each of the HBsAg decline groups


Continuous HBsAg decline is associated with high rates of sustained immune control
60% of patients with a continuous HBsAg decline achieved sustained immune control 6 months post-treatment and 38% had sustained immune control 5 years post-treatment (Figure 2)
Late decline was also associated with good rates of sustained immune control; 48% of patients with late decline had sustained immune control 6 months post-treatment and 21% sustained immune control 5 years post-treatment




1. Brunetto M et al. Hepatitis B virus surface antigen levels - a guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B. Hepatology 2009; 49:1141-1150
2. Marcellin P et al. Increasing rates of HBsAg clearance and seroconversion in patients with HBeAg-negative disease treated with peginterferon alfa-2a ± lamivudine: results of 5-year post-treatment follow-up. J Hepatol 2009; 50(suppl 1):S336
3. Brunetto M et al. PEGASYS-treated patients with HBV genotype D achieve sustained response 5 years post-treatment and on-treatment HBsAg decline. Presented at the 5th APASL Single Topic Conference, 17-20th May 2009, Istanbul, Turkey
4. Moucari R et al. Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients. Hepatology 2009; 49:1151-1157
5. Rijckborst V et al. Early reduction of serum HBsAg levels in HBeAg-negative chronic hepatitis B patients achieving sustained virological response after peginterferon alfa-2a ± ribavirin treatment. Hepatol 2008; 48(suppl 1):A986
6. Lampertico P et al. A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis Be antigen in serum. Hepatol 1997; 26:1621-1625
7. Lampertico P et al. Long-term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24- month interferon therapy. Hepatol 2003; 37:756-763
8. Gish RG et al. A pilot study of extended duration peginterferon alfa-2a for patients with hepatitis B e antigen-negative chronic hepatitis B. Am J Gastroenterol 2007; 102:2718-2723
9. Marcellin P et al. Peginterferon alfa 2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. New Engl J Med 2004; 351:1206-1217