Current Hepatitis Reports

, Volume 6, Issue 1, pp 24–29

Chronic hepatitis B virus infection in patients with “Normal” ALT levels



Not many data exist to guide us in the management of patients with chronic hepatitis B virus infection and “normal” alanine aminotransferase levels. Many of these patients may not have normal levels on long-term follow-up or when the upper limit of normal is determined from a truly healthy reference population. These patients may have significant histologic disease and benefit from further investigation or treatment. This article focuses on the disease course of such patients.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Lok AS:Chronic heptitis B.N Engl J Med 2002,346:1682–1683.PubMedCrossRefGoogle Scholar
  2. 2.
    Yim HJ, Lok AS:Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005.Hepatology 2006,43:S173-S181.PubMedCrossRefGoogle Scholar
  3. 3.
    Keffee EB, Dieterich DT, Han SB, et al.:A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update.Clin Gastroenterol Hepatol 2006,4:936–962.CrossRefGoogle Scholar
  4. 4.
    Chu CM, Liaw YF, Chu CM, Liaw YF:Genotype C hepatitis B virus infection is associated with a higher risk of reactivation of hepatitis B and progression to cirrhosis than genotype B: a longitudinal study of hepatitis B e antigenpositive patients with normal aminotransferase levels at baseline.J Hepatol 2005,43:411–417.PubMedCrossRefGoogle Scholar
  5. 5.
    EASL Jury:EASL International Consensus Conference on Hepatitis B.J Hepatol 2003,38:533–540.Google Scholar
  6. 6.
    Colin JF, Cazals-Hatem D, Loriot MA, et al.:Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men.Hepatology 1999,29:1306–1310.PubMedCrossRefGoogle Scholar
  7. 7.
    McMahon BJ:Epidemiology and natural history of hepatitis B.Semin Liver Dis 2005,25(suppl 1):3–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Chwla Y:Hepatitis B virus: inactive carriers.Virol J 2005,2:82.PubMedCrossRefGoogle Scholar
  9. 9.
    Chu CM, Liaw YF:Hepatitis B virus-related cirrhosis: natural history and treatment.Semin Liver Dis 2006,26:142–152.PubMedCrossRefGoogle Scholar
  10. 10.
    Liaw YF:Prevention and surveillance of hepatitis B virus-related hepatocellular carcinoma.Semin Liver Dis 2005,25(suppl 1):40–47.PubMedCrossRefGoogle Scholar
  11. 11.
    Fattovich G, Giustina G, Schalm SW, et al.:Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis.Hepatology 1995,21:77–82.PubMedGoogle Scholar
  12. 12.
    Locarnini S:Molecular virology of hepatitis B virus.Semin Liver Dis 2004,24(suppl 1):3–10.PubMedCrossRefGoogle Scholar
  13. 13.
    Liu CJ, Lo SC, Kao JH, et al.:Transmission of occult hepatitis B virus by transfusion to adult and pediatric recipients in Taiwan.J Hepatol 2006,44:39–46.PubMedCrossRefGoogle Scholar
  14. 14.
    Bonino F, Brunetto MR:Hepatitis B virus heterogeneity, one of many factors influencing the severity of hepatitis B.J Hepatol 1993,18:5–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Sunbul M, Leblebicioglu H:Distribution of hepatitis B virus genotypes in patients with chronic hepatitis B in Turkey.World J Gastroenterol 2005,11:1976–1980.PubMedGoogle Scholar
  16. 16.
    Zacharakis GH, Koskinas J, Kotsiou S, et al.:Natural history of chronic HBV infection: a cohort study with up to 12 years follow-up in North Greece (part of the Interreg I-II/EC-project).J Med Virol 2005,77:173–179.PubMedCrossRefGoogle Scholar
  17. 17.
    Yang HI, Lu SN, Liaw YF, et al.:Hepatitis B e antigen and the risk of hepatocellular carcinoma.N Engl J Med 2002,347:168–174.PubMedCrossRefGoogle Scholar
  18. 18.
    Zollner B, Feucht HH, Sterneck M, et al.:Clinical reactivation after liver transplantation with an unusual minor strain of hepatitis B virus in an occult carrier.Liver Transpl 2006,12:1283–1289.PubMedCrossRefGoogle Scholar
  19. 19.
    Mindikoglu AL, Regev A, Schiff ER:Hepatitis B virus reactivation after cytotoxic chemotherapy: the disease and its prevention.Clin Gastroenterol Hepatol 2006,4:1076–1081.PubMedCrossRefGoogle Scholar
  20. 20.
    Kohrt HE, Ouyang DL, Keeffee EB:Systematic review: lamivudine prophylaxis for chemotherapy-induced reactivation of chronic hepatitis B virus infection.Aliment Pharmacol Ther 2006,24:1003–1016.PubMedCrossRefGoogle Scholar
  21. 21.
    Dai MS, Kao WY, Shyu RY, Chao TY:Restoration of immunity and reactivation of hepatitis B virus after immunosuppressive therapy in a patient with severe aplastic anaemia.J Viral Hepat 2004,11:283–285.PubMedCrossRefGoogle Scholar
  22. 22.
    Dai MS, Wu PF, Lu JJ, et al.:Preemptive use of lamivudine in breast cancer patients carrying hepatitis B virus undergoing cytotoxic chemotherapy: a longitudinal study.Support Care Cancer 2004,12:191–196.PubMedCrossRefGoogle Scholar
  23. 23.
    Buckwold VE, Xu Z, Chen M, et al.:Effects of a naturally occurring mutation in the hepatitis B virus basal core promoter on precore gene expression and viral replication.J Virol 1996,70:5845–5851.PubMedGoogle Scholar
  24. 24.
    Brunetto MR, Oliveri F, Rocca G, et al.:Natural course and response to interferon of chronic hepatitis B accompanied by antibody to hepatitis B e antigen.Hepatology 1989;10:198–202.PubMedCrossRefGoogle Scholar
  25. 25.
    Peng XM, Huang GM, Li JG, et al.:High level of hepatitis B virus DNA after HBeAg-to-anti-HBe seroconversion is related to coexistence of mutations in its precore and basal core promoter.World J Gastroenterol 2005,11:3131–3134.PubMedGoogle Scholar
  26. 26.
    Lok AS, Lai CL, Wu PC, et al.:Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection.Gastroenterology 1987,92:1839–1843.PubMedGoogle Scholar
  27. 27.
    Liaw YF, Chu CM, Lin DY, et al.:Age-specific prevalence and significance of hepatitis B e antigen and antibody in chronic hepatitis B virus infection in Taiwan: a comparison among asymptomatic carriers, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.J Med Virol 1984,13:385–391.PubMedCrossRefGoogle Scholar
  28. 28.
    Lok AS, Lai CL:A longitudinal follow-up of asymptomatic hepatitis B surface antigen-positive Chinese children.Hepatology 1988,8:1130–1133.PubMedCrossRefGoogle Scholar
  29. 29.
    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.PubMedCrossRefGoogle Scholar
  30. 30.
    Liu CJ, Chen BF, Chen PJ, et al.:Role of hepatitis B virus precore/core promoter mutations and serum viral load on noncirrhotic hepatocellular carcinoma: a case-control study.J Infect Dis 2006,194:594–599.PubMedCrossRefGoogle Scholar
  31. 31.
    Lampertico P, Del Ninno E, Manzin A, et al.:A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum.Hepatology 1997,26:1621–1625.PubMedCrossRefGoogle Scholar
  32. 32.
    Yuen M-F, Yuan H-J, Wong DK-H, et al.:Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications.Gut 2005,54:1610–1614.PubMedCrossRefGoogle Scholar
  33. 33.
    Niederau C, Heintges T, Lange S, et al.:Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B.N Engl J Med 1996,334:1422–1427.PubMedCrossRefGoogle Scholar
  34. 34.
    Chen G, Lin WY, Shen FM, et al.:Viral load as a predictor of mortality from hepatocellular carcinoma and chronic liver disease in chronic hepatitis B infection [abstract].J Hepatol 2005,42:172A.Google Scholar
  35. 35.
    Kariv R, Leshno M, Beth-Or A, et al.:Re-evaluation of serum alanine aminotransferase upper normal limit and its modulating factors in a large-scale population study.Liver Int 2006,26:445–450.PubMedCrossRefGoogle Scholar
  36. 36.
    Prati D, Taioli E, Zanella A, et al.:Updated definitions of healthy ranges for serum alanine aminotransferase levels.Ann Intern Med 2002,137:1–10.PubMedGoogle Scholar
  37. 37.
    Nguyen MH, Trinh H, Garcia RT, Keefe EG:Significant histological disease in HBV-infected patients with normal to minimally elevated ALT levels at initial evaluation [abstract].Hepatology 2005,42:593A.Google Scholar
  38. 38.
    Shiffman ML, Diago M, Tran A, et al.:Chronic hepatitis C in patients with persistently normal alanine transaminase levels.Clin Gastroenterol Hepatol 2006,4:645–652.PubMedCrossRefGoogle Scholar
  39. 39.
    Persico M, Perrotta S, Persico E, et al.:Hepatitis C virus carriers with persistently normal ALT levels: biological peculiarities and update of the natural history of liver disease at 10 years.J Viral Hepat 2006,13:290–296.PubMedCrossRefGoogle Scholar
  40. 40.
    Perieira HM, Cavalheiro NP, Tengan FM, et al.:Patients with chronic hepatitis C and normal transaminases.Rev Inst Med Trop Sao Paulo 2005,47:247–251.Google Scholar
  41. 41.
    Gonzalez S, Liu R, Edlin BR, et al.:HIV/hepatitis C virus-coinfected patients with normal alanine aminotransferase levels.J Acquir Immune Defic Syndr 2006,41:582–589.PubMedCrossRefGoogle Scholar
  42. 42.
    Kim HC, Nam CM, Jee SH, et al.:Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study.BMJ 2004,328:983.PubMedCrossRefGoogle Scholar
  43. 43.
    Lai M, Hyatt B, Afdahl N:The role of liver biopsy in patients with normal ALT and high HBV DNA [abstract].Hepatology 2005,42:720A.Google Scholar
  44. 44.
    Wang C, Deubner H, Shuhart M, et al.:High prevalence of significant fibrosis in patients with immunotolerance to chronic hepatitis B infection [abstract].Hepatology 2005,42:573A.Google Scholar
  45. 45.
    Iloeje UH, Yang HI, Su J, et al.; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group:Predicting cir-rhosis risk based on the level of circulating hepatitis B viral load.Gastroenterology 2006,130:678–686.PubMedCrossRefGoogle Scholar
  46. 46.
    Chen CJ, Yang HI, Su J, et al.; REVEAL-HBV Study Group:Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.JAMA 2006,295:65–73.PubMedCrossRefGoogle Scholar
  47. 47.
    Park HH, Song IH, Chung YH, et al.:Chronic hepatitis B in hepatocarcinogenesis.Postgrad Med J 2006,82:507–515.PubMedCrossRefGoogle Scholar
  48. 48.
    Beasley RP:Hepatitis B virus as the etiologic agent in hepatocellular carcinoma.Hepatology 1982,2(suppl):21S.Google Scholar
  49. 49.
    Sakuma K, Saitoh N, Kasai M, et al.:Relative risks of death due to liver disease among Japanese male adults having various statuses for hepatitis B s and e antigen/antibody in serum: a prospective study.Hepatology 1988;8:1642–1646.PubMedCrossRefGoogle Scholar
  50. 50.
    Beasley RP, Hwang LY, Lin CC, Chien CS:Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan.Lancet 1981,2(8256):1129–1133.PubMedCrossRefGoogle Scholar
  51. 51.
    Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases:Management of hepatocellular carcinoma.Hepatology 2005,42:1208–1236.PubMedCrossRefGoogle Scholar
  52. 52.
    Sherman M, Peltekian KM, Lee C:Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population.Hepatology 1995,22:432–438.PubMedGoogle Scholar
  53. 53.
    Van Thiel DH, Gavaler JS, Wright H, Tzakis A:Liver biopsy. Its safety and complications as seen at a liver transplant center.Transplantation 1993,55:1087–1090.PubMedCrossRefGoogle Scholar
  54. 54.
    Bravo AA, Sheth SG, Chopra S:Liver biopsy.N Engl J Med 2001,344:495–500.PubMedCrossRefGoogle Scholar
  55. 55.
    McGill DB, Rakela J, Zinsmeister AR, Ott BJ:A 21-year experience with major hemorrhage after percutaneous liver biopsy.Gastroenterology 1990,99:1396–1400.PubMedGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.Division of Gastroenterology and HepatologyStanford University Medical CenterPalo AltoUSA

Personalised recommendations