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Published in: Hepatology International 1/2013

Open Access 01-03-2013 | Original Article

Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients

Authors: Patrick Marcellin, Ferruccio Bonino, Cihan Yurdaydin, Stephanos Hadziyannis, Rami Moucari, Hans-Peter Kapprell, Vivien Rothe, Matei Popescu, Maurizia R. Brunetto

Published in: Hepatology International | Issue 1/2013

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Abstract

Purpose

To investigate the durability of response to peginterferon alfa-2a up to 5 years post-treatment and factors associated with response in hepatitis B e-antigen (HBeAg)-negative patients.

Methods

HBeAg-negative patients received peginterferon alfa-2a (180 μg/week) ± lamivudine (100 mg/day) for 48 weeks as part of a multicenter, randomized study. The planned 5-year efficacy analysis included patients (n = 230) enrolled in the long-term follow-up study. On-treatment hepatitis B surface antigen (HBsAg) decline kinetics were analyzed retrospectively in a subgroup of patients with HBsAg data available at baseline, weeks 12, 24, and 48 on-treatment, and 6 months post-treatment (n = 120). Receiver operating characteristic analyses identified the on-treatment HBsAg levels associated with response at 1 and 5 years post-treatment.

Results

HBV DNA ≤2,000 IU/mL and HBsAg clearance at 5 years post-treatment were achieved by 23 and 12% of patients, respectively. High rates of HBsAg clearance at 5 years post-treatment were achieved by patients with HBV DNA ≤2,000 IU/mL at 1 year post-treatment (28%). Rates of HBV DNA ≤2,000 IU/mL at 1 year post-treatment were 47.2 and 43.4% in patients with ≥10% decline from baseline at weeks 12 and 24, respectively, compared with 16.4% (p = 0.0003) and 13.2% (p < 0.0004) in patients with a <10% decline. Rates of HBsAg clearance at 5 years post-treatment were 22.6 and 22.4% in patients with ≥10% decline at weeks 12 and 24, respectively, compared with 7.5% (p = 0.0161) and 3.8% (p < 0.0001) in patients with <10% decline.

Conclusions

Peginterferon alfa-2a results in increasing rates of HBsAg clearance during post-treatment follow-up in HBeAg-negative patients. On-treatment decline in HBsAg is significantly associated with long-term post-treatment response.
Literature
1.
go back to reference Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009;50:1–36 Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009;50:1–36
2.
go back to reference European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 2009;50:227–242CrossRef European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 2009;50:227–242CrossRef
3.
go back to reference Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 2008;48:335–352PubMedCrossRef Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 2008;48:335–352PubMedCrossRef
4.
go back to reference Yang HI, Lu SN, Liaw YF, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 2002;347:168–174PubMedCrossRef Yang HI, Lu SN, Liaw YF, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 2002;347:168–174PubMedCrossRef
5.
go back to reference Simonetti J, Bulkow L, McMahon BJ, et al. Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus. Hepatology 2010;51:1531–1537PubMedCrossRef Simonetti J, Bulkow L, McMahon BJ, et al. Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus. Hepatology 2010;51:1531–1537PubMedCrossRef
6.
go back to reference Manesis EK, Hadziyannis SJ. Interferon alfa treatment and retreatment of hepatitis B e antigen-negative chronic hepatitis B. Gastroenterology 2001;121:101–109PubMedCrossRef Manesis EK, Hadziyannis SJ. Interferon alfa treatment and retreatment of hepatitis B e antigen-negative chronic hepatitis B. Gastroenterology 2001;121:101–109PubMedCrossRef
7.
go back to reference Marcellin P, Bonino F, Lau GK, et al. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alfa-2a. Gastroenterology 2009;136:2169–2179PubMedCrossRef Marcellin P, Bonino F, Lau GK, et al. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alfa-2a. Gastroenterology 2009;136:2169–2179PubMedCrossRef
9.
go back to reference Chen C-J, Iloeje UJ, Yang HI. Long-term outcomes in hepatitis B: the REVEAL-HBV study. Clin Liver Dis 2007;11:797–816PubMedCrossRef Chen C-J, Iloeje UJ, Yang HI. Long-term outcomes in hepatitis B: the REVEAL-HBV study. Clin Liver Dis 2007;11:797–816PubMedCrossRef
10.
go back to reference Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006;295:65–73PubMedCrossRef Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006;295:65–73PubMedCrossRef
11.
go back to reference Lampertico P, Del Ninno E, Viganò M, et al. Long-term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy. Hepatology 2003;37:756–763PubMedCrossRef Lampertico P, Del Ninno E, Viganò M, et al. Long-term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy. Hepatology 2003;37:756–763PubMedCrossRef
12.
go back to reference Brunetto MR, Oliveri F, Coco B, et al. Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long-term cohort study. J Hepatol 2002;36:263–270PubMedCrossRef Brunetto MR, Oliveri F, Coco B, et al. Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long-term cohort study. J Hepatol 2002;36:263–270PubMedCrossRef
13.
go back to reference Marcellin P, Lau GK, Bonino F, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2004;351:1206–1217PubMedCrossRef Marcellin P, Lau GK, Bonino F, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2004;351:1206–1217PubMedCrossRef
14.
go back to reference Moucari R, Mackiewicz V, Lada O, et al. Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients. Hepatology 2009;49:1151–1157PubMedCrossRef Moucari R, Mackiewicz V, Lada O, et al. Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients. Hepatology 2009;49:1151–1157PubMedCrossRef
15.
go back to reference Manesis EK, Hadziyannis ES, Angelopoulou OP, et al. Prediction of treatment-related HBsAg loss in HBeAg-negative chronic hepatitis B: a clue from serum HBsAg levels. Antivir Ther 2007;12:73–82PubMed Manesis EK, Hadziyannis ES, Angelopoulou OP, et al. Prediction of treatment-related HBsAg loss in HBeAg-negative chronic hepatitis B: a clue from serum HBsAg levels. Antivir Ther 2007;12:73–82PubMed
16.
go back to reference Kuhns MC, Kleinman SH, McNamara AL, et al. Lack of correlation between HBsAg and HBV DNA levels in blood donors who test positive for HBsAg and anti-HBc: implications for future HBV screening policy. Transfusion 2004;44:1332–1339PubMedCrossRef Kuhns MC, Kleinman SH, McNamara AL, et al. Lack of correlation between HBsAg and HBV DNA levels in blood donors who test positive for HBsAg and anti-HBc: implications for future HBV screening policy. Transfusion 2004;44:1332–1339PubMedCrossRef
17.
go back to reference Brunetto MR, Moriconi F, Bonino F, 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;49:1141–1150PubMedCrossRef Brunetto MR, Moriconi F, Bonino F, 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;49:1141–1150PubMedCrossRef
18.
go back to reference Chang TT, Lai CL, Kew Yoon S, et al. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology 2010;51:422–430PubMedCrossRef Chang TT, Lai CL, Kew Yoon S, et al. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology 2010;51:422–430PubMedCrossRef
19.
go back to reference Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumerate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med 2008;359:2442–2455PubMedCrossRef Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumerate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med 2008;359:2442–2455PubMedCrossRef
20.
go back to reference Nguyen T, Thompson AJ, Bowden S, et al. Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: a perspective on Asia. J Hepatol 2010;52:508–513PubMedCrossRef Nguyen T, Thompson AJ, Bowden S, et al. Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: a perspective on Asia. J Hepatol 2010;52:508–513PubMedCrossRef
21.
go back to reference Jaroszewicz J, Calle Serrano B, Wursthorn K, et al. Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: a European perspective. J Hepatol 2010;52:514–522PubMedCrossRef Jaroszewicz J, Calle Serrano B, Wursthorn K, et al. Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: a European perspective. J Hepatol 2010;52:514–522PubMedCrossRef
22.
go back to reference Bonino F, Marcellin P, Lau GK, et al. Predicting response to peginterferon-alpha-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B. Gut 2007;56:699–705PubMedCrossRef Bonino F, Marcellin P, Lau GK, et al. Predicting response to peginterferon-alpha-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B. Gut 2007;56:699–705PubMedCrossRef
23.
go back to reference Moucari R, Martinot-Peignoux M, Mackiewicz V, et al. Influence of genotype of hepatitis B surface antigen kinetics in hepatitis B e antigen-negative patients treated with pegylated interferon-alpha2a. Antivir Ther 2009;14:1183–1188PubMedCrossRef Moucari R, Martinot-Peignoux M, Mackiewicz V, et al. Influence of genotype of hepatitis B surface antigen kinetics in hepatitis B e antigen-negative patients treated with pegylated interferon-alpha2a. Antivir Ther 2009;14:1183–1188PubMedCrossRef
24.
go back to reference Rijckborst V, Hansen BE, Cakaloglu Y, et al. Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels. Hepatology 2010;52:454–461PubMedCrossRef Rijckborst V, Hansen BE, Cakaloglu Y, et al. Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels. Hepatology 2010;52:454–461PubMedCrossRef
25.
go back to reference Lampertico P, Vigano M, Di Costanzo G, et al. Extended (2 years) treatment with peginterferon alfa-2a (40KD) improves sustained response rates in genotype D patients with HBeAg negative chronic hepatitis B. J Hepatol 2010;52(Suppl. 1):S45CrossRef Lampertico P, Vigano M, Di Costanzo G, et al. Extended (2 years) treatment with peginterferon alfa-2a (40KD) improves sustained response rates in genotype D patients with HBeAg negative chronic hepatitis B. J Hepatol 2010;52(Suppl. 1):S45CrossRef
26.
go back to reference Brunetto MR, Marcellin P, Bonino F et al. 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. Hepatology (2010) 50 Suppl 4:137A (P452) Brunetto MR, Marcellin P, Bonino F et al. 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. Hepatology (2010) 50 Suppl 4:137A (P452)
Metadata
Title
Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients
Authors
Patrick Marcellin
Ferruccio Bonino
Cihan Yurdaydin
Stephanos Hadziyannis
Rami Moucari
Hans-Peter Kapprell
Vivien Rothe
Matei Popescu
Maurizia R. Brunetto
Publication date
01-03-2013
Publisher
Springer-Verlag
Published in
Hepatology International / Issue 1/2013
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-012-9343-x

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