Skip to main content
SpringerLink
Log in
Book cover

Hepatitis B Virus and Liver Disease pp 181–191Cite as

Chronic HBV Infection: Interferon Therapy and Long-Term Outcomes

  • Chapter
  • First Online:

Abstract

Chronic hepatitis B infection affects around 240 million people worldwide, with long-term morbidity such as cirrhosis and hepatocellular carcinoma. Interferon treatment enhanced HBsAg seroclearance. Pegylated interferon induced a 10-15% yearly rate of HBsAg seroclearance in patients who developed sustained virological response in clinical trials. By contrast, treatment with nucleos (t) ides analogues did not significantly affect the rate of HBsAg seroclearance, especially in patients with hepatitis B e antigen (HBeAg) - negative disease. Recently, it has been shown that a significantly greater proportion of patients receiving tenofovir plus pegylated-interferon for 48 weeks had HBsAg loss than those receiving tenofovir or pegylated-interferon alone. HBsAg clearance is the closest to cure outcome, and there is increasing interest in HBsAg quantification. Quantification of serum HBsAg has also been recently shown to be a promising tool for monitoring virologic response in HBeAg-negative patients treated with pegylated interferon. This chapter reviews Interferon therapy and long-term outcomes.

This is a preview of subscription content, log in via an institution.

Abbreviations

AE:

Adverse event

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

cccDNA:

Covalently closed circular DNA

CHB:

Chronic hepatitis B

ETV:

Entecavir

HBeAg:

HBe antigen

HBsAg:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

IFN:

Interferon

NAs:

Nucleos(t)ide analogues

NI:

Nucleoside inhibitors

NNI:

Non-nucleoside inhibitors

PEG-IFN:

Pegylated interferon

QD:

Once daily

TDF:

Tenofovir

References

  • Appourchaux K, Dokmak S, Resche-Rigon M, Treton X, Lapalus M, Gattolliat CH, Porchet E, Martinot-Peignoux M, Boyer N, Vidaud M, Bedossa P, Marcellin P, Bièche I, Estrabaud E, Asselah T. MicroRNA-based diagnostic tools for advanced fibrosis and cirrhosis in patients with chronic hepatitis B and C. Sci Rep. 2016;6:34935. https://doi.org/10.1038/srep34935.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Asselah T, Marcellin P, Bedossa P. Improving performance of liver biopsy in fibrosis assessment. J Hepatol. 2014;61(2):193–5.

    Article  PubMed  Google Scholar 

  • Bonino F, Marcellin P, Lau GKK, et al. Predicting response to peginterferon alfa-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B. Gut. 2007;56:699–705.

    Article  CAS  PubMed  Google Scholar 

  • Brunetto MR, Moriconi F, Bononi 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;49:1141–50.

    Article  CAS  PubMed  Google Scholar 

  • Buster EH, Flink HJ, Cakaloglu Y, et al. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alfa-2b. Gastroenterology. 2008;135:459–67.

    Article  CAS  PubMed  Google Scholar 

  • Chan HL, Wong VW, Chim AM, et al. Serum HBsAg quantification to predict response to peginterferon therapy of e antigen positive chronic hepatitis B. Aliment Pharmacol Ther. 2010;32:1323–15.

    Article  CAS  PubMed  Google Scholar 

  • European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–85.

    Article  Google Scholar 

  • Flink HJ, van Zonneveld M, Hansen BE, et al., HBV99-01study group. Treatment with Peg-interferon alpha-2b for HBe-Ag positive chronic hepatitis B: HBs loss is associated with genotype. Am J Gastroenterol. 2006;101:297–303.

    Google Scholar 

  • Holmes JA, Nguyen T, Ratnam D, Heerasing NM, Tehan JV, Bonanzinga S, Dev A, Bell S, Pianko S, Chen R, Visvanathan K, Hammond R, Iser D, Rusli F, Sievert W, Desmond PV, Bowden DS, Thompson AJ. IL28B genotype is not useful for predicting treatment outcome in Asian chronic hepatitis B patients treated with pegylated interferon-α. J Gastroenterol Hepatol. 2013;28(5):861–6.

    Article  CAS  PubMed  Google Scholar 

  • Lai CL, Chien RN, Leung NW, et al. A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N Engl J Med. 1998;339:61–8.

    Article  CAS  PubMed  Google Scholar 

  • Lampertico P, Viganò M, Cheroni C, Facchetti F, Invernizzi F, Valveri V, Soffredini R, Abrignani S, De Francesco R, Colombo M. IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen-negative patients with chronic hepatitis B. Hepatology. 2013;57(3):890–6.

    Article  CAS  PubMed  Google Scholar 

  • Lau GK, Piratvisuth T, Luo KX, et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352:2682–95.

    Article  CAS  PubMed  Google Scholar 

  • Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521–31.

    Article  CAS  PubMed  Google Scholar 

  • Marcellin P, Asselah T. Long-term therapy for chronic hepatitis B: hepatitis B virus DNA suppression leading to cirrhosis reversal. J Gastroenterol Hepatol. 2013;28:912–23.

    Article  CAS  PubMed  Google Scholar 

  • Marcellin P, Asselah T, Boyer N. Fibrosis and disease progression in hepatitis C. Hepatology. 2002;36(5 Suppl 1):S47–56.

    PubMed  Google Scholar 

  • 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;351:1206–17.

    Article  CAS  PubMed  Google Scholar 

  • Marcellin P, Bonino F, Lau GK, et al. Peginterferon alfa-2a in HBeAg-negative Chronic Hepatitis B Study Group. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a. Gastroenterology. 2009;136:2169–79.

    Article  CAS  PubMed  Google Scholar 

  • Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013a;318:468–75.

    Article  Google Scholar 

  • Marcellin P, Bonino F, Yurdayin C, et al. Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients. Hepatol Int. 2013b;7:88–97.

    Article  PubMed  Google Scholar 

  • Marcellin P, Martinot-Peignoux M, Asselah T, Batrla R, Messinger D, Rothe V, Lau G, Liaw YF. Serum levels of hepatitis B surface antigen predict severity of fibrosis in patients with E antigen-positive chronic hepatitis B. Clin Gastroenterol Hepatol. 2015;13(8):1532–9.e1.

    Article  CAS  PubMed  Google Scholar 

  • Marcellin P, Ahn SH, Ma X, et al. Combination of tenofovir disoproxil fumarate and peginterferon alpha-2a increases loss of hepatitis B surface antigen in patients with chronic hepatitis B. Gastroenterology. 2016;150(1):134–44.

    Article  CAS  PubMed  Google Scholar 

  • Martinot-Peignoux M, Carvalho-Filho R, Lapalus M, et al. Hepatitis B surface antigen serum level is associated with fibrosis severity in treatment-naıve, e antigen-positive patients. J Hepatol. 2013;58:1089–95.

    Article  CAS  PubMed  Google Scholar 

  • Martinot-Peignoux M, Lapalus M, Asselah T, Marcellin P. HBsAg quantification: useful for monitoring natural history and treatment outcome. Liver Int. 2014;34(Suppl. 1):97–107.

    Article  CAS  PubMed  Google Scholar 

  • Martinot-Peignoux M, Asselah T, Marcellin P. HBsAg quantification to optimize treatment monitoring in chronic hepatitis B patients. Liver Int. 2015;35(Suppl):82–90.

    Article  CAS  PubMed  Google Scholar 

  • Martinot-Peignoux M, Lapalus M, Maylin S, Boyer N, Castelnau C, Giuily N, Pouteau M, Moucari R, Asselah T, Marcellin P. Baseline HBsAg and HBcrAg titres allow peginterferon-based ‘precision medicine’ in HBeAg-negative chronic hepatitis B patients. J Viral Hepat. 2016;23(11):905–11.

    Article  CAS  PubMed  Google Scholar 

  • Moucari R, Korevaar A, Lada O, Martinot-Peignoux M, Boyer N, Mackiewicz V, Dauvergne A, Cardoso AC, Asselah T, Nicolas-Chanoine MH, Vidaud M, Valla D, Bedossa P, Marcellin P. High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study. J Hepatol. 2009a;50(6):1084–92.

    Article  CAS  PubMed  Google Scholar 

  • 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. 2009b;49:1151–7.

    Article  CAS  PubMed  Google Scholar 

  • Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1–98.

    Article  CAS  PubMed  Google Scholar 

  • Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH, American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261–83.

    Article  PubMed  Google Scholar 

  • Wiegand J, Hasenclever D, Tillmann H. Should treatment of hepatitis B depend on hepatitis B virus genotypes? A hypothesis generated from an explorative analysis of published evidence. Antivir Ther. 2008;13:211–20.

    CAS  PubMed  Google Scholar 

  • World Health Organization. Hepatitis B Fact sheet No. 204. 2012 [Cited 2012 Oct 24]. Available from: http://www.who.int/mediacentre/factsheets/fs204/en/

  • Wu HL, Hsiao TH, Chen PJ, Wong SH, Kao JH, Chen DS, Lu JY, Lu TP, Chen Y, Chuang EY, Tu HC, Liu CJ. Liver gene expression profiles correlate with virus infection and response to interferon therapy in chronic hepatitis B patients. Sci Rep. 2016;6:31349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Q, Lapalus M, Asselah T, Laouénan C, Moucari R, Martinot-Peignoux M, Bieche I, Estrabaud E, De Muynck S, Boyer N, Bedossa P, Vidaud M, Marcellin P, Lada O. IFNL3 (IL28B) polymorphism does not predict long-term response to interferon therapy in HBeAg-positive chronic hepatitis B patients. J Viral Hepat. 2014;21(7):525–32.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflicts of Interest

Tarik Asselah is a speaker and investigator for BMS, Boehringer Ingelheim, Tibotec, Janssen, Gilead, Roche, and MSD.

Patrick Marcellin is a speaker and investigator for BMS, Boehringer Ingelheim, Tibotec, Janssen, Gilead, Roche, and MSD.

Author information

Authors and Affiliations

  1. UMR1149, Team “Physiopathologie et traitements des hépatites virales”, Centre de Recherche sur l’Inflammation, Paris, France

    Tarik Asselah M.D., Ph.D. & Patrick Marcellin

  2. Hepatology Department, Beaujon Hospital, Université Denis Diderot Paris 7, AP-HP, 100 Bd du Général Leclerc, Clichy, 92110, France

    Tarik Asselah M.D., Ph.D. & Patrick Marcellin

Authors
  1. Tarik Asselah M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick Marcellin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tarik Asselah M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

    Jia-Horng Kao

  2. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Genomics Research CenterAcademia Sinica, Taipei, Taiwan

    Ding-Shinn Chen

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Asselah, T., Marcellin, P. (2018). Chronic HBV Infection: Interferon Therapy and Long-Term Outcomes. In: Kao, JH., Chen, DS. (eds) Hepatitis B Virus and Liver Disease. Springer, Singapore. https://doi.org/10.1007/978-981-10-4843-2_10

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-4843-2_10

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-4842-5

  • Online ISBN: 978-981-10-4843-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation