Semin Liver Dis 2007; 27: 003-008
DOI: 10.1055/s-2007-984694
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Halting the Natural History of Hepatitis B Viral Infection: A Paradigm Shift

Robert P. Perrillo1 , Ira M. Jacobson2
  • 1Hepatology Division, Baylor University Medical Center, Dallas, Texas
  • 2Division of Gastroenterology and Hepatology, Weill Medical College of Cornell University, New York, New York
Further Information

Publication History

Publication Date:
14 August 2007 (online)

ABSTRACT

The 2007 American Association for the Study of Liver Diseases (AASLD) practice guidelines for managing chronic hepatitis B virus (HBV) infection recommend pharmacologic therapy for patients with alanine aminotransferase (ALT) activity higher than 2 times the upper limit of normal and serum HBV DNA concentration higher than 20,000 IU/mL. Findings reported over the past several years, however, indicate that HBV infection associated with ALT activity and serum HBV DNA concentrations below these treatment thresholds can progress to serious liver disease, such as cirrhosis or hepatocellular carcinoma. These findings suggest that these treatment thresholds may be too conservative. Moreover, emerging data suggest that, in some patient populations, the appropriate goal of therapy may be sustained suppression of HBV DNA with maintenance antiviral therapy. A satellite symposium conducted during the 57th Annual Meeting of the AASLD in Boston, Massachusetts, presented new findings relative to the course of HBV infection.

REFERENCES

  • 1 World Heath Organization .Hepatitis B 2000Available at: http://www.who.int/mediacentre/factsheets/fs204/en Accessed June 6, 2006. 
  • 2 Centers for Disease Control and Prevention (CDC) . Incidence of acute hepatitis B: United States, 1990-2002.  MMWR Morb Mortal Wkly Rep. 2004;  52 1252-1254
  • 3 Beasley R P. Hepatitis B virus: the major etiology of hepatocellular carcinoma.  Cancer. 1988;  61 1942-1956
  • 4 The Organ Procurement and Transplantation Network .Organ by diagnosis. Current U.S. waiting listAvailable at: http://www.optn.org/latestData/step2.asp? Accessed December 5, 2006. 
  • 5 Lok A S, McMahon B J. Practice Guidelines Committee, American Association for the Study of Liver Diseases . Chronic hepatitis B.  Hepatology. 2001;  34 1225-1241
  • 6 Lok ASF, McMahon B J. Chronic hepatitis B.  Hepatology. 2007;  45 507-539
  • 7 Lau D T, Everhart J, Kleiner D E et al.. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa.  Gastroenterology. 1997;  113 1660-1667
  • 8 van Zonneveld M, Honkoop P, Hansen B E et al.. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B.  Hepatology. 2004;  39 804-810
  • 9 Perrillo R P. Therapy of hepatitis B: viral suppression or eradication?.  Hepatology. 2006;  43(suppl 1) S182-S193
  • 10 Liaw Y F. The current management of HBV drug resistance.  J Clin Virol. 2005;  34(suppl 1) S143-S146
  • 11 Locarnini S. Molecular virology and the development of resistant mutants: implications for therapy.  Semin Liver Dis. 2005;  25(suppl 1) 9-19
  • 12 Chen C J, Yang H I, Su J et al.. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.  JAMA. 2006;  295 65-73
  • 13 Iloeje U H, Yang H I, Su J et al.. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load.  Gastroenterology. 2006;  130 678-686
  • 14 Kim H C, Nam C M, Jee S H et al.. Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study.  BMJ. 2004;  328 983
  • 15 Yang L M, Xu K C, Zhao Y L et al.. Clinical significance of liver biopsy in chronic hepatitis B patients with persistently normal transaminase.  Chin J Dig Dis. 2002;  3 150-153
  • 16 Yuen M F, Yuan H J, Wong D K et al.. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications.  Gut. 2005;  54 1610-1614
  • 17 Fattovich G, Rugge M, Brollo L et al.. Clinical, virologic and histologic outcome following seroconversion from HBeAg to anti-HBe in chronic hepatitis type B.  Hepatology. 1986;  6 167-172
  • 18 Hoofnagle J H, Dusheiko G M, Seeff L B et al.. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis.  Ann Intern Med. 1981;  94 744-748
  • 19 Manesis E K, Papatheodoridis G V, Sevastianos V et al.. Significance of hepatitis B viremia levels determined by a quantitative polymerase chain reaction assay in patients with hepatitis B e antigen-negative chronic hepatitis B virus infection.  Am J Gastroenterol. 2003;  98 2261-2267
  • 20 Evans A A, Fabre R E, Chen G et al.. Hepatitis B viral load is associated with the development of hepatocellular carcinoma (HCC).  Hepatology. 2004;  40(suppl 1) 602A
  • 21 Yang H I, Lu S N, Liaw Y F et al.. Hepatitis B e antigen and the risk of hepatocellular carcinoma.  N Engl J Med. 2002;  347 168-174
  • 22 Chu C J, Hussain M, Lok A S. Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection.  Hepatology. 2002;  36 1408-1415
  • 23 Lai C L, Chien R N, Leung N W et al.. A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.  N Engl J Med. 1998;  339 61-68
  • 24 Dienstag J L, Schiff E R, Wright T L et al.. Lamivudine as initial treatment for chronic hepatitis B in the United States.  N Engl J Med. 1999;  341 1256-1263
  • 25 Zoulim F, Poynard T, Degos F et al.. A prospective study of the evolution of lamivudine resistance mutations in patients with chronic hepatitis B treated with lamivudine.  J Viral Hepat. 2006;  13 278-288
  • 26 Yuen M F, Sablon E, Hui C K, Yuan H J, Decraemer H, Lai C L. Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy.  Hepatology. 2001;  34 785-791
  • 27 Lai C L, Gane E, Hsu C W et al.. Two-year results from the GLOBE Trial in patients with hepatitis B: greater clinical and antiviral efficacy for telbivudune (LDT) vs lamivudine.  Hepatology. 2006;  44(suppl 1) 222A
  • 28 Lok A S, Lai C L, Leung N et al.. Long-term safety of lamivudine treatment in patients with chronic hepatitis B.  Gastroenterology. 2003;  125 1714-1722
  • 29 Lai C L, Dienstag J, Schiff E et al.. Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B.  Clin Infect Dis. 2003;  36 687-696
  • 30 Heo J, Cho M, Cho B M et al.. Predictors of lamivudine resistance in patients with chronic hepatitis B infection.  Korean J Hepatol. 2007;  13 157-165
  • 31 Hadziyannis S J, Tassopoulos N C, Heathcote E J et al.. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years.  Gastroenterology. 2006;  131 1743-1751
  • 32 DiBisceglie A, Lai C L, Gane E et al.. Telbivudine GLOBE Trial: maximal early HBV suppression is predictive of optimal two-year efficacy in nucleoside-treated hepatitis B patients.  Hepatology. 2006;  44(suppl 1) 230A-231A
  • 33 Colonno R J, Rose R, Baldick C J et al.. Entecavir resistance is rare in nucleoside naive patients with hepatitis B.  Hepatology. 2006;  44 1656-1665
  • 34 Colonno R J, Rose R E, Pokornowski K et al.. Four year assessment of entecavir resistance in nucleoside naive and lamivudine refractory patients. Presented at: 42nd Annual Meeting of the European Association for the study of Liver Disease. April 11-15, 2007 Barcelona, Spain;

Robert P PerrilloM.D. 

Baylor University Medical Center

3500 Gaston Avenue, 4 Roberts, Dallas, TX 75246

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