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Hepatitis B surface antigen: association with sustained response to peginterferon alfa-2a in hepatitis B e antigen-positive patients

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Abstract

Purpose

Patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, who achieve HBeAg seroconversion 6 months after completing 48 weeks of peginterferon alfa-2a therapy, have an increased chance of clearing hepatitis B surface antigen (HBsAg) during long-term treatment-free follow-up. This analysis aimed to determine whether HBsAg quantification during treatment could be used to identify posttreatment response.

Methods

Patients (n = 399) treated with peginterferon alfa-2a (180 μg/week) alone or in combination with lamivudine (100 mg/day) for 48 weeks during a large, randomized study were included in this retrospective analysis. Receiver-operating characteristic analyses were used to identify baseline and on-treatment HBsAg levels associated with response (HBeAg seroconversion 6 months posttreatment).

Results

Baseline HBsAg levels were lower in patients achieving posttreatment response than in nonresponders (3.97 and 4.21 IU/mL, respectively, p = 0.039). Two baseline HBsAg cutoff levels (5,000 and 50,000 IU/mL) provided a positive predictive value of 42% and a negative predictive value of 77%. HBsAg decline was significantly greater during and posttreatment in responders than in nonresponders (p < 0.0001). HBeAg seroconversion rates 6 months posttreatment were significantly higher in patients with HBsAg < 1,500 IU/mL at weeks 12 and 24 (56.7 and 54.4%, respectively) versus patients with HBsAg 1,500–20,000 IU/mL (32.3 and 26.1%, respectively) or HBsAg < 20,000 IU/mL (16.3 and 15.4%, respectively) (all p < 0.0001 and <0.0001).

Conclusions

HBsAg levels at baseline strongly associated with posttreatment response were not identified. Low HBsAg levels during peginterferon alfa-2a therapy were associated with high rates of posttreatment response. On-treatment HBsAg quantification may, therefore, help guide patient management in the future.

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Acknowledgements

Research grant was provided by F. Hoffmann-La Roche, Basel, Switzerland. Editorial support was provided by Dr Liesje Thomas of Elements Communications Ltd., Westerham, UK.

Conflict of interest

TP has participated in advisory boards for Roche, Novartis, MSD and GSK, in Speaker’s Bureau for Roche, Novartis, MSD, GSK and BMS, and has received research grants from Roche and Novartis. PM has acted as a speaker for Roche, Schering-Plough, Gilead, BMS, Novartis, Tibotec, and Intermune; has acted as an expert for Roche, Schering-Plough, Gilead, BMS, Verex, Novartis, Pharmasset, Tibotec, MSD, Biolex, Zymogenetics and Intermune; as an investigator for Roche, Schering-Plough, Gilead, BMS, Verex, Novartis, Tibotec, MSD, Biolex and Intermune; and has received grant support from Roche, Schering-Plough and Gilead. EBM is an employee of Genentech. H-PK is an employee of Abbott GmbH and Company. All other authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand

    Teerha Piratvisuth

  2. Service d’Hépatologie U773-CRB3, Hôpital Beaujon, University of Paris, Clichy, France

    Patrick Marcellin

  3. F.Hoffmann-La Roche, Basel, Switzerland

    Matei Popescu

  4. Abbott GmbH and Company, Wiesbaden-Delkenheim, Germany

    Hans-Peter Kapprell

  5. IST GmbH, Mannheim, Germany

    Vivien Rothe

  6. Department of Infectious Diseases, Ruijin Hospital, Shanghai, China

    Zhi-Meng Lu

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  1. Teerha Piratvisuth
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  2. Patrick Marcellin
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  6. Zhi-Meng Lu
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Correspondence to Teerha Piratvisuth.

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Piratvisuth, T., Marcellin, P., Popescu, M. et al. Hepatitis B surface antigen: association with sustained response to peginterferon alfa-2a in hepatitis B e antigen-positive patients. Hepatol Int 7, 429–436 (2013). https://doi.org/10.1007/s12072-011-9280-0

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  • DOI: https://doi.org/10.1007/s12072-011-9280-0

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