Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Overview of the management of hepatitis B and case examples

Anna SF Lok, MD
Section Editor
Rafael Esteban, MD
Deputy Editor
Jennifer Mitty, MD, MPH


The following topic review will summarize issues related to the management of hepatitis B. These recommendations (and the data supporting them) are discussed in detail in their corresponding topic reviews. In addition, the recommendations below are generally consistent with guidelines from the European consensus statement (EASL), Asian-Pacific consensus statement, and American Association for the Study of Liver Diseases Practice Guidelines [1-4]. Specific examples of cases are described at the end, which illustrate some of the issues that may arise when making treatment decisions for patients with chronic hepatitis B. Clinical decisions regarding individual patients should be based upon patient-specific clinical information and test results.

Topic reviews that discuss the management of pregnant women and children with hepatitis B virus infection, as well as the data supporting this section are presented separately. (See "Hepatitis B and pregnancy" and "Overview of hepatitis B virus infection in children and adolescents" and "Standard and pegylated interferon for chronic hepatitis B virus infection" and "Lamivudine monotherapy for chronic hepatitis B virus infection" and "Adefovir dipivoxil in the treatment of chronic hepatitis B virus infection" and "Entecavir in the treatment of chronic hepatitis B virus infection" and "Telbivudine in the treatment of chronic hepatitis B virus infection" and "Efficacy of tenofovir disoproxil fumarate in the treatment of adults with chronic HBV infection who do not have HIV infection".)


The hepatitis B virus (HBV) is a double-stranded DNA virus belonging to the family of hepadnaviruses, which include duck hepatitis virus, woodchuck hepatitis virus, and ground squirrel hepatitis virus. (See "Characteristics of the hepatitis B virus and pathogenesis of infection".)

HBV has traditionally been classified into eight genotypes (A to H) based upon an inter-group divergence of 8 percent or more in the complete nucleotide sequence. Two additional genotypes, I and J, have subsequently been reported. The prevalence of specific genotypes varies geographically. Furthermore, genotypes may correlate with clinical course and response to interferon. Genotype testing is not necessary in routine clinical practice, but it may be indicated for HBeAg-positive patients who are considering interferon therapy since patients with genotype A have a more favorable response. (See "Clinical significance of hepatitis B virus genotypes" and "Clinical significance and molecular characteristics of common hepatitis B virus variants".)


Hepatitis B virus infection is a global public health problem. It is estimated that there are more than 250 million HBV carriers in the world, of whom approximately 600,000 die annually from HBV-related liver disease. Despite the availability of HBV vaccines, the rate of HBV-related hospitalizations, cancers, and deaths in the United States have more than doubled during the past decade. (See "Epidemiology, transmission, and prevention of hepatitis B virus infection".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Apr 8, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Liaw YF, Leung N, Kao JH, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int 2008; 2:263.
  2. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009; 50:661.
  3. European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012; 57:167.
  4. Terrault NA, Bzowej NH, Chang KM, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016; 63:261.
  5. Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep 2006; 55:1.
  6. Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep 2005; 54:1.
  7. Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep 2008; 57:1.
  8. Wong GL, Wong VW, Choi PC, et al. Evaluation of alanine transaminase and hepatitis B virus DNA to predict liver cirrhosis in hepatitis B e antigen-negative chronic hepatitis B using transient elastography. Am J Gastroenterol 2008; 103:3071.
  9. Lai M, Hyatt BJ, Nasser I, et al. The clinical significance of persistently normal ALT in chronic hepatitis B infection. J Hepatol 2007; 47:760.
  10. Kumar M, Sarin SK, Hissar S, et al. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT. Gastroenterology 2008; 134:1376.
  11. Andreani T, Serfaty L, Mohand D, et al. Chronic hepatitis B virus carriers in the immunotolerant phase of infection: histologic findings and outcome. Clin Gastroenterol Hepatol 2007; 5:636.
  12. Hui CK, Leung N, Yuen ST, et al. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase. Hepatology 2007; 46:395.
  13. Sorrell MF, Belongia EA, Costa J, et al. National Institutes of Health Consensus Development Conference Statement: management of hepatitis B. Ann Intern Med 2009; 150:104.
  14. Yapali S, Talaat N, Lok AS. Management of hepatitis B: our practice and how it relates to the guidelines. Clin Gastroenterol Hepatol 2014; 12:16.
  15. Sinn DH, Lee J, Goo J, et al. Hepatocellular carcinoma risk in chronic hepatitis B virus-infected compensated cirrhosis patients with low viral load. Hepatology 2015; 62:694.
  16. Marcellin P, Gane EJ, Flisiak R, et al. Long Term Treatment with Tenofovir Disoproxil Fumarate for Chronic Hepatitis B Infection is Safe and Well Tolerated and Associated with Durable Virologic Response with no Detectable Resistance: 8 Year Results from Two Phase 3 Trials. American Association for the Study of Liver Diseases (AASLD) Liver Meeting. Boston, November 7-12, 2014. Abstract 229.
  17. Chien RN, Liaw YF, Atkins M. Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B. Asian Hepatitis Lamivudine Trial Group. Hepatology 1999; 30:770.
  18. Perrillo RP, Lai CL, Liaw YF, et al. Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B. Hepatology 2002; 36:186.
  19. Yapali S, Lok AS. Potential benefit of telbivudine on renal function does not outweigh its high rate of antiviral drug resistance and other adverse effects. Gastroenterology 2014; 146:15.
  20. Lim YS, Byun KS, Yoo BC, et al. Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure: results of a randomised trial. Gut 2016; 65:852.
  21. Köklü S, Tuna Y, Gülşen MT, et al. Long-term efficacy and safety of lamivudine, entecavir, and tenofovir for treatment of hepatitis B virus-related cirrhosis. Clin Gastroenterol Hepatol 2013; 11:88.
  22. Lo AO, Wong VW, Wong GL, et al. Cost effectiveness of response-guided therapy with peginterferon in the treatment of chronic hepatitis B. Clin Gastroenterol Hepatol 2015; 13:377.
  23. Liaw YF, Leung N, Guan R, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update. Liver Int 2005; 25:472.
  24. Papatheodoridis G, Viachogiannakos I, Cholongitas, et al. Discontinuation of oral antivirals in chronic hepatitis B: a systematic review. Hepatology 2016; doi:10.1002/hep28438.
  25. Chang ML, Jeng WJ, Liaw YF. Clinical events after cessation of lamivudine therapy in patients recovered from hepatitis B flare with hepatic decompensation. Clin Gastroenterol Hepatol 2015; 13:979.
  26. Tenney DJ, Rose RE, Baldick CJ, et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy. Hepatology 2009; 49:1503.
  27. Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med 2006; 354:1001.
  28. Ahn J, Lee HM, Lim JK, et al. Entecavir safety and effectiveness in a national cohort of treatment-naïve chronic hepatitis B patients in the US - the ENUMERATE study. Aliment Pharmacol Ther 2016; 43:134.
  29. Seto WK, Hui AJ, Wong VW, et al. Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study. Gut 2015; 64:667.
  30. Jeng WJ, Sheen IS, Chen YC, et al. Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients. Hepatology 2013; 58:1888.
  31. Kumar M, Satapathy S, Monga R, et al. A randomized controlled trial of lamivudine to treat acute hepatitis B. Hepatology 2007; 45:97.
  32. Chan HL, Chan CK, Hui AJ, et al. Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA. Gastroenterology 2014; 146:1240.
  33. Centers for Disease Control and Prevention (CDC). Updated CDC recommendations for the management of hepatitis B virus-infected health-care providers and students. MMWR Recomm Rep 2012; 61:1.
  34. Lok AS, Trinh H, Carosi G, et al. Efficacy of entecavir with or without tenofovir disoproxil fumarate for nucleos(t)ide-naïve patients with chronic hepatitis B. Gastroenterology 2012; 143:619.
Topic Outline