Skip to main content

Advertisement

SpringerLink
Log in

Current Management of Hepatitis B in 2016

  • Hepatitis B (JK Lim, Section Editor)
  • Published:
Current Hepatology Reports Aims and scope Submit manuscript

Abstract

Chronic hepatitis B infection represents a global public health burden, infecting over 240 million persons worldwide. It is associated with significant morbidity and mortality and represents a leading cause for cirrhosis, liver failure, liver cancer, and liver-related death. Current treatment of hepatitis B is focused on identification of patients with active hepatitis within the immune clearance or reactivation phases of chronic infection, for whom antiviral therapy with peg-interferon or nucleos(t)ide analogs are recommended. Seven antiviral agents are currently approved by the US FDA for treatment of chronic hepatitis B, of which three are recommended as first-line agents by major liver societies. As none are associated with virologic cure, the primary objective of antiviral therapy in 2016 is long-term virologic suppression, which is associated with a decreased risk for cirrhosis and hepatocellular carcinoma, and may reverse liver fibrosis or cirrhosis in some patients. Although biochemical improvement in liver enzymes is common, HBeAg seroconversion occurs in only a minority of patients, and HBsAg seroconversion is rare. Due to ongoing deficits along multiple steps of the care cascade, including screening, diagnosis, linkage to care, and antiviral therapy, many patients with chronic hepatitis B remain undiagnosed, lack access to care by specialists with expertise in the management of CHB, or have not been treated with antiviral agents. Future therapies are currently in development with the aim of functional viral cure, which may transform the treatment of CHB and improve liver outcomes.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30(12):2212–9. doi:10.1016/j.vaccine.2011.12.116.

    Article  CAS  PubMed  Google Scholar 

  2. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095–128. doi:10.1016/S0140-6736(12)61728-0.

    Article  PubMed  Google Scholar 

  3. Ganem D, Prince AM. Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med. 2004;350(11):1118–29. doi:10.1056/NEJMra031087.

    Article  CAS  PubMed  Google Scholar 

  4. Wasley A, Kruszon-Moran D, Kuhnert W, Simard EP, Finelli L, McQuillan G, et al. The prevalence of hepatitis B virus infection in the United States in the era of vaccination. J Infect Dis. 2010;202(2):192–201. doi:10.1086/653622.

    Article  PubMed  Google Scholar 

  5. Kowdley KV, Wang CC, Welch S, Roberts H, Brosgart CL. Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin. Hepatology. 2012;56(2):422–33. doi:10.1002/hep.24804.

    Article  PubMed  Google Scholar 

  6. Cohen C, Evans AA, London WT, Block J, Conti M, Block T. Underestimation of chronic hepatitis B virus infection in the United States of America. J Viral Hepat. 2008;15(1):12–3. doi:10.1111/j.1365-2893.2007.00888.x.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. • Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261–83. doi:10.1002/hep.28156. This manuscript represents an updated consensus guideline of the American Association for the Study of Liver Diseases (AASLD) which uses GRADE methodology to address key clinical issues in the management of chronic hepatitis B infection, and incorporates updated evidence to inform clinical decision-making.

  8. Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352(26):2682–95. doi:10.1056/NEJMoa043470.

    Article  CAS  PubMed  Google Scholar 

  9. Marcellin P, Lau GK, Bonino F, Farci P, Hadziyannis S, Jin R, 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(12):1206–17. doi:10.1056/NEJMoa040431.

    Article  CAS  PubMed  Google Scholar 

  10. Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354(10):1001–10. doi:10.1056/NEJMoa051285.

    Article  CAS  PubMed  Google Scholar 

  11. Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2006;354(10):1011–20. doi:10.1056/NEJMoa051287.

    Article  CAS  PubMed  Google Scholar 

  12. Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008;359(23):2442–55. doi:10.1056/NEJMoa0802878.

    Article  CAS  PubMed  Google Scholar 

  13. Wong DK, Cheung AM, O’Rourke K, Naylor CD, Detsky AS, Heathcote J. Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann Intern Med. 1993;119(4):312–23.

    Article  CAS  PubMed  Google Scholar 

  14. Chang TT, Lai CL, Kew Yoon S, Lee SS, Coelho HS, Carrilho FJ, et al. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology. 2010;51(2):422–30. doi:10.1002/hep.23327.

    Article  CAS  PubMed  Google Scholar 

  15. Gish RG, Lok AS, Chang TT, de Man RA, Gadano A, Sollano J, et al. Entecavir therapy for up to 96 weeks in patients with HBeAg-positive chronic hepatitis B. Gastroenterology. 2007;133(5):1437–44. doi:10.1053/j.gastro.2007.08.025.

    Article  CAS  PubMed  Google Scholar 

  16. Buti M, Tsai N, Petersen J, Flisiak R, Gurel S, Krastev Z, et al. Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection. Dig Dis Sci. 2015;60(5):1457–64. doi:10.1007/s10620-014-3486-7.

    Article  CAS  PubMed  Google Scholar 

  17. Zoutendijk R, Reijnders JG, Brown A, Zoulim F, Mutimer D, Deterding K, et al. Entecavir treatment for chronic hepatitis B: adaptation is not needed for the majority of naïve patients with a partial virological response. Hepatology. 2011;54(2):443–51. doi:10.1002/hep.24406.

    Article  CAS  PubMed  Google Scholar 

  18. Buti M, Morillas RM, Prieto M, Diago M, Pérez J, Solà R, et al. Efficacy and safety of entecavir in clinical practice in treatment-naive Caucasian chronic hepatitis B patients. Eur J Gastroenterol Hepatol. 2012;24(5):535–42. doi:10.1097/MEG.0b013e3283511287.

    Article  CAS  PubMed  Google Scholar 

  19. Ono A, Suzuki F, Kawamura Y, Sezaki H, Hosaka T, Akuta N, et al. Long-term continuous entecavir therapy in nucleos(t)ide-naïve chronic hepatitis B patients. J Hepatol. 2012;57(3):508–14. doi:10.1016/j.jhep.2012.04.037.

    Article  CAS  PubMed  Google Scholar 

  20. Ridruejo E, Marciano S, Galdame O, Reggiardo MV, Muñoz AE, Adrover R, et al. Efficacy and safety of long term entecavir in chronic hepatitis B treatment naïve patients in clinical practice. Ann Hepatol. 2014;13(3):327–36.

    PubMed  Google Scholar 

  21. Choi HN, Song JE, Lee HC, Jo HH, Lee CH, Kim BS. Efficacy of prolonged entecavir monotherapy in treatment-naïve chronic hepatitis B patients exhibiting a partial virologic response to entecavir. Clin Mol Hepatol. 2015;21(1):24–31. doi:10.3350/cmh.2015.21.1.24.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Petersen J, Heyne R, Mauss S, Schlaak J, Schiffelholz W, Eisenbach C, et al. Effectiveness and safety of tenofovir disoproxil fumarate in chronic hepatitis B: a 3-year prospective field practice study in Germany. Dig Dis Sci. 2015. doi:10.1007/s10620-015-3960-x.

    Google Scholar 

  23. Marcellin P, Zoulim F, Hézode C, Causse X, Roche B, Truchi R, et al. Effectiveness and safety of tenofovir disoproxil fumarate in chronic hepatitis B: a 3-year, prospective, real-world study in France. Dig Dis Sci. 2016. doi:10.1007/s10620-015-4027-8.

    PubMed  PubMed Central  Google Scholar 

  24. Kim JH, Jung SW, Byun SS, Shin JW, Park BR, Kim MH, et al. Efficacy and safety of tenofovir in nucleos(t)ide-naïve patients with genotype C chronic hepatitis B in real-life practice. Int J Clin Pharm. 2015;37(6):1228–34. doi:10.1007/s11096-015-0193-1.

    Article  CAS  PubMed  Google Scholar 

  25. Wang HM, Hung CH, Lee CM, Lu SN, Wang JH, Yen YH, et al. Three-year efficacy and safety of tenofovir in nucleos(t)ide analog-naïve and -experienced chronic hepatitis B patients. J Gastroenterol Hepatol. 2016. doi:10.1111/jgh.13294.

    PubMed Central  Google Scholar 

  26. Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130(3):678–86. doi:10.1053/j.gastro.2005.11.016.

    Article  PubMed  Google Scholar 

  27. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1):65–73. doi:10.1001/jama.295.1.65.

    Article  CAS  PubMed  Google Scholar 

  28. Iloeje UH, Yang HI, Jen CL, Su J, Wang LY, You SL, et al. Risk and predictors of mortality associated with chronic hepatitis B infection. Clin Gastroenterol Hepatol. 2007;5(8):921–31. doi:10.1016/j.cgh.2007.06.015.

    Article  PubMed  Google Scholar 

  29. Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351(15):1521–31. doi:10.1056/NEJMoa033364.

    Article  CAS  PubMed  Google Scholar 

  30. Lok AS, McMahon BJ, Brown RS, Wong JB, Ahmed AT, Farah W, et al. Antiviral therapy for chronic hepatitis B viral infection in adults: a systematic review and meta-analysis. Hepatology. 2016;63(1):284–306. doi:10.1002/hep.28280.

    Article  CAS  PubMed  Google Scholar 

  31. Chang TT, Liaw YF, Wu SS, Schiff E, Han KH, Lai CL, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52(3):886–93. doi:10.1002/hep.23785.

    Article  CAS  PubMed  Google Scholar 

  32. Schiff ER, Lee SS, Chao YC, Kew Yoon S, Bessone F, Wu SS, et al. Long-term treatment with entecavir induces reversal of advanced fibrosis or cirrhosis in patients with chronic hepatitis B. Clin Gastroenterol Hepatol. 2011;9(3):274–6. doi:10.1016/j.cgh.2010.11.040.

    Article  CAS  PubMed  Google Scholar 

  33. •• Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381(9865):468–75. doi:10.1016/S0140-6736(12)61425-1. This manuscript represents a landmark paper which provided the most robust evidence that long-term antiviral suppression with tenofovir is associated with stable or reduced liver fibrosis over five years of treatment, and may result in regression of liver cirrhosis to lesser degrees of liver fibrosis in nearly three-quarters of patients.

  34. Ning Q, Han M, Sun Y, Jiang J, Tan D, Hou J, et al. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). J Hepatol. 2014;61(4):777–84. doi:10.1016/j.jhep.2014.05.044.

    Article  CAS  PubMed  Google Scholar 

  35. Hadziyannis SJ, Sevastianos V, Rapti I, Vassilopoulos D, Hadziyannis E. Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir. Gastroenterology. 2012;143(3):629–36.e1. doi:10.1053/j.gastro.2012.05.039.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Yale Liver Center, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, LMP 1080, New Haven, CT, 06520-8019, USA

    Arpan Mohanty & Joseph K. Lim

Authors
  1. Arpan Mohanty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph K. Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joseph K. Lim.

Ethics declarations

Conflict of Interest

Dr. Arpan Mohanty declares no conflict of interest.

Dr. Joseph Lim declares that he has received research contracts (to Yale University) and consulting honoraria from Bristol-Myers Squibb and Gilead.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Hepatitis B

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohanty, A., Lim, J.K. Current Management of Hepatitis B in 2016. Curr Hepatology Rep 15, 266–270 (2016). https://doi.org/10.1007/s11901-016-0323-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11901-016-0323-9

Keywords

Search

Navigation