Hepatitis B Clinical Presentation

  • Author: Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP; Chief Editor: Julian Katz, MD   more...
 
Updated: Dec 29, 2011
 

History

The spectrum of the symptomatology of hepatitis B disease varies from subclinical hepatitis to icteric hepatitis to hyperacute, acute, and subacute hepatitis during the acute phase, and from an asymptomatic carrier state to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) during the chronic phase.

Acute phase

The incubation period is 1-6 months in the acute phase.

Anicteric hepatitis is the predominant form of expression for this disease. The majority of the patients are asymptomatic, but patients with anicteric hepatitis have a greater tendency to develop chronic hepatitis. Patients with symptomatology have the same symptoms as patients who develop icteric hepatitis.

Icteric hepatitis is associated with a prodromal period, during which a serum sickness –like syndrome can occur. The symptomatology is more constitutional and includes the following:

  • Anorexia
  • Nausea
  • Vomiting
  • Low-grade fever
  • Myalgia
  • Fatigability
  • Disordered gustatory acuity and smell sensations (aversion to food and cigarettes)
  • Right upper quadrant and epigastric pain (intermittent, mild to moderate)

Patients with hyperacute, acute, and subacute hepatitis may present with the following:

  • Hepatic encephalopathy
  • Somnolence
  • Disturbances in sleep pattern
  • Mental confusion
  • Coma

Chronic phase

Patients with chronic hepatitis B disease can be healthy carriers without any evidence of active disease, and they also are asymptomatic.

Patients with chronic active hepatitis, especially during the replicative state, may complain of symptomatology such as the following:

  • Symptoms similar to those of acute hepatitis
  • Fatigue
  • Anorexia
  • Nausea
  • Mild upper quadrant pain or discomfort
  • Hepatic decompensation
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Physical Examination

The physical examination findings in hepatitis B disease vary from minimal to impressive (patients with hepatic decompensation) according to the stage of disease.

Patients with acute hepatitis usually do not have any clinical findings, but the physical examination can reveal the following:

  • Low-grade fever
  • Jaundice (10 d after the appearance of constitutional symptomatology and lasting for 1-3 mo)
  • Hepatomegaly (mildly enlarged soft liver)
  • Splenomegaly (5-15%)
  • Palmar erythema (rarely)
  • Spider nevi (rarely)

The physical examination of patients with chronic hepatitis B virus (HBV) infection can reveal stigmata of chronic liver disease such as the following:

  • Hepatomegaly
  • Palmar erythema
  • Spider angioma

Patients with cirrhosis may have the following symptoms:

  • Ascites
  • Jaundice
  • History of variceal bleeding
  • Peripheral edema
  • Gynecomastia
  • Testicular atrophy
  • Abdominal collateral veins (caput medusa)
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Staging

Liver damage is graded according to the inflammatory component and is described as follows:

  • Grade 0 – Portal inflammation only, no activity
  • Grade 1 – Minimal portal inflammation and patchy lymphocytic necrosis, with minimal lobular inflammation and spotty necrosis
  • Grade 2 – Mild portal inflammation and lymphocytic necrosis involving some or all portal tracts, with mild hepatocellular damage
  • Grade 3 – Moderate portal inflammation and lymphocytic necrosis involving all portal tracts, with noticeable lobular inflammation and hepatocellular change
  • Grade 4 – Severe portal inflammation and severe lymphocytic bridging necrosis, with severe lobular inflammation and prominent diffuse hepatocellular damage

Liver damage staging (ie, fibrosis) is described as follows:

  • Stage 0 – No fibrosis
  • Stage 1 – Portal fibrosis
  • Stage 2 – Periportal fibrosis
  • Stage 3 – Septal, bridging fibrosis (see the image below)Liver biopsy with trichrome stain showing stage 3 Liver biopsy with trichrome stain showing stage 3 fibrosis in a patient with hepatitis B.
  • Stage 4 – Cirrhosis (see the following image)Liver biopsy with hematoxylin stain showing stage Liver biopsy with hematoxylin stain showing stage 4 fibrosis (ie, cirrhosis) in a patient with hepatitis B.
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Contributor Information and Disclosures
Author

Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP  Chair of Hepatology, Medical Director of Liver Transplantation, Liver Unit, Florida Hospital; Associate Professor of Medicine, University of Central Florida College of Medicine

Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Liver Foundation, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Transplantation, International Liver Transplantation Society, and Transplantation Society

Disclosure: Gilead Sciences Honoraria Speaking and teaching; Schering-Plough Honoraria Speaking and teaching; Roche Honoraria Speaking and teaching

Coauthor(s)

K Rajender Reddy, MD, FACP, FACG  Professor of Medicine, Director of Hepatology, Medical Director of Liver Transplantation, Hospital of the University of Pennsylvania

K Rajender Reddy, MD, FACP, FACG is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and Florida Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Additional Contributors

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

George Y Wu, MD, PhD Professor, Department of Medicine, Director, Hepatology Section, Herman Lopata Chair in Hepatitis Research, University of Connecticut School of Medicine

George Y Wu, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Medical Association, American Society for Clinical Investigation, and Association of American Physicians

Disclosure: Springer Consulting fee Consulting; Gilead Consulting fee Review panel membership; Gilead Honoraria Speaking and teaching; Bristol-Myers Squibb Honoraria Speaking and teaching; Springer Royalty Review panel membership

References

  1. Purcell RH. The discovery of the hepatitis viruses. Gastroenterology. Apr 1993;104(4):955-63. [Medline].

  2. Fattovich G, Giustina G, Schalm SW, Hadziyannis S, Sanchez-Tapias J, Almasio P, 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. Jan 1995;21(1):77-82. [Medline].

  3. Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med. Jun 26 1997;336(26):1855-9. [Medline].

  4. Yu MC, Yuan JM, Ross RK, Govindarajan S. Presence of antibodies to the hepatitis B surface antigen is associated with an excess risk for hepatocellular carcinoma among non-Asians in Los Angeles County, California. Hepatology. Jan 1997;25(1):226-8. [Medline].

  5. Yang HI, Yeh SH, Chen PJ, Iloeje UH, Jen CL, Su J, et al. Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma. J Natl Cancer Inst. Aug 20 2008;100(16):1134-43. [Medline]. [Full Text].

  6. Blumberg BS. Australia antigen and the biology of hepatitis B. Science. Jul 1 1977;197(4298):17-25. [Medline].

  7. Norder H, Couroucé AM, Magnius LO. Complete genomes, phylogenetic relatedness, and structural proteins of six strains of the hepatitis B virus, four of which represent two new genotypes. Virology. Feb 1994;198(2):489-503. [Medline].

  8. Lau JY, Wright TL. Molecular virology and pathogenesis of hepatitis B. Lancet. Nov 27 1993;342(8883):1335-40. [Medline].

  9. Chisari FV, Ferrari C. Hepatitis B virus immunopathology. Springer Semin Immunopathol. 1995;17(2-3):261-81. [Medline].

  10. Davies SE, Portmann BC, O'Grady JG, Aldis PM, Chaggar K, Alexander GJ, et al. Hepatic histological findings after transplantation for chronic hepatitis B virus infection, including a unique pattern of fibrosing cholestatic hepatitis. Hepatology. Jan 1991;13(1):150-7. [Medline].

  11. Jung MC, Diepolder HM, Pape GR. T cell recognition of hepatitis B and C viral antigens. Eur J Clin Invest. Oct 1994;24(10):641-50. [Medline].

  12. Chisari FV. Cytotoxic T cells and viral hepatitis. J Clin Invest. Apr 1 1997;99(7):1472-7. [Medline]. [Full Text].

  13. Dong Q, Liu Z, Chen Y, Chan CY, Lin MC, Kung HF, et al. High level virion production and surface antigen expression with 1.5 copies of hepatitis B viral genome. J Virol Methods. Aug 2009;159(2):135-40. [Medline].

  14. Eckman MH, Kaiser TE, Sherman KE. The cost-effectiveness of screening for chronic hepatitis B infection in the United States. Clin Infect Dis. Jun 2011;52(11):1294-306. [Medline]. [Full Text].

  15. Centers for Disease Control and Prevention. Hepatitis B Information for Health Professionals. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/hepatitis/HBV/index.htm. Accessed November 1, 2011.

  16. Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. Clin Gastroenterol Hepatol. Aug 2006;4(8):936-62. [Medline].

  17. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. Feb 2007;45(2):507-39. [Medline].

  18. Mutimer D, Naoumov N, Honkoop P, Marinos G, Ahmed M, de Man R, et al. Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study. J Hepatol. Jun 1998;28(6):923-9. [Medline].

  19. 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. Aug 15 1993;119(4):312-23. [Medline].

  20. Tseng TC, Liu CJ, Su TH, et al. Serum Hepatitis B Surface Antigen Levels Predict Surface Antigen Loss in Hepatitis B e Antigen Seroconverters. Gastroenterology. Aug 2011;141(2):517-525.e2. [Medline].

  21. 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. Jun 30 2005;352(26):2682-95. [Medline].

  22. Schnittman SM, Pierce PF. Potential role of lamivudine (3TC) in the clearance of chronic hepatitis B virus infection in a patient coinfected with human immunodeficiency virus type. Clin Infect Dis. Sep 1996;23(3):638-9. [Medline].

  23. Dienstag JL, Schiff ER, Wright TL, Perrillo RP, Hann HW, Goodman Z, et al. Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med. Oct 21 1999;341(17):1256-63. [Medline].

  24. Grellier L, Mutimer D, Ahmed M, Brown D, Burroughs AK, Rolles K, et al. Lamivudine prophylaxis against reinfection in liver transplantation for hepatitis B cirrhosis. Lancet. Nov 2 1996;348(9036):1212-5. [Medline].

  25. Tipples GA, Ma MM, Fischer KP, Bain VG, Kneteman NM, Tyrrell DL. Mutation in HBV RNA-dependent DNA polymerase confers resistance to lamivudine in vivo. Hepatology. Sep 1996;24(3):714-7. [Medline].

  26. Honkoop P, Niesters HG, de Man RA, Osterhaus AD, Schalm SW. Lamivudine resistance in immunocompetent chronic hepatitis B. Incidence and patterns. J Hepatol. Jun 1997;26(6):1393-5. [Medline].

  27. Yang H, Westland CE, Delaney WE 4th, Heathcote EJ, Ho V, Fry J, et al. Resistance surveillance in chronic hepatitis B patients treated with adefovir dipivoxil for up to 60 weeks. Hepatology. Aug 2002;36(2):464-73. [Medline].

  28. Villeneuve JP, Durantel D, Durantel S, Westland C, Xiong S, Brosgart CL, et al. Selection of a hepatitis B virus strain resistant to adefovir in a liver transplantation patient. J Hepatol. Dec 2003;39(6):1085-9. [Medline].

  29. Angus P, Vaughan R, Xiong S, Yang H, Delaney W, Gibbs C, et al. Resistance to adefovir dipivoxil therapy associated with the selection of a novel mutation in the HBV polymerase. Gastroenterology. Aug 2003;125(2):292-7. [Medline].

  30. Chang TT, Lai CL. Hepatitis B virus with primary resistance to adefovir. N Engl J Med. Jul 20 2006;355(3):322-3; author reply 323. [Medline].

  31. Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. Feb 27 2003;348(9):808-16. [Medline].

  32. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med. Jun 30 2005;352(26):2673-81. [Medline].

  33. Tenney D, Pokornowski K, Rose RE, et al. Entecavir maintains a high genetic barrier to HBV resistance through 6 years in naive patients [abstract]. Hepatology. 2009;50(Suppl 2):S10.

  34. 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. Mar 9 2006;354(10):1001-10. [Medline].

  35. Lai C-L, Gane E, Liaw Y-F, et al. Telbivudine (LdT) vs. lamivudine for chronic hepatitis B: first-year results from the international phase III GLOBE Trial [abstract]. Hepatology. 2005;42:748A.

  36. Liaw YF, Gane E, Leung N, Zeuzem S, Wang Y, Lai CL, et al. 2-Year GLOBE trial results: telbivudine Is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology. Feb 2009;136(2):486-95. [Medline].

  37. Heathcote J, George J, Gordon S, et al. Tenofovir disoproxil fumarate (TDF) for the treatment of HBeAg-positive chronic hepatitis B: week 72 TDF data and week 24 adefovir dipivoxil switch data (study 103) [abstract]. J Hepatol. 2008;(suppl):S26.

  38. Marcellin P, Jacobson I, Habersetzer F, et al. Tenofovir disoproxil fumarate (TDF) for the treatment of HBeAg-negative chronic hepatitis B: week 72 TDF data and week 24 adefovir dipivoxil switch data (study 102) [abstract]. J Hepatol. 2008;48:S26.

  39. 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. Dec 4 2008;359(23):2442-55. [Medline].

  40. Guillevin L, Mahr A, Cohen P, et al. Short-term corticosteroids then lamivudine and plasma exchanges to treat hepatitis B virus-related polyarteritis nodosa. Arthritis Rheum. Jun 15 2004;51(3):482-7. [Medline].

  41. Caputo R, Gelmetti C, Ermacora E, Gianni E, Silvestri A. Gianotti-Crosti syndrome: a retrospective analysis of 308 cases. J Am Acad Dermatol. Feb 1992;26(2 Pt 1):207-10. [Medline].

  42. Use of Hepatitis B Vaccination for Adults with Diabetes Mellitus: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. Dec 23 2011;60:1709-11. [Medline].

  43. Juday T, Tang H, Harris M, Powers AZ, Kim E, Hanna GJ. Adherence to chronic hepatitis B treatment guideline recommendations for laboratory monitoring of patients who are not receiving antiviral treatment. J Gen Intern Med. Mar 2011;26(3):239-44. [Medline]. [Full Text].

  44. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. Dec 2006;131(6):1743-51. [Medline].

  45. 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. Sep 16 2004;351(12):1206-17. [Medline].

  46. Tang KH, Yusoff K, Tan WS. Display of hepatitis B virus PreS1 peptide on bacteriophage T7 and its potential in gene delivery into HepG2 cells. J Virol Methods. Aug 2009;159(2):194-9. [Medline].

  47. Thibault V, Laperche S, Akhavan S, Servant-Delmas A, Belkhiri D, Roque-Afonso AM. Impact of hepatitis B virus genotypes and surface antigen variants on the performance of HBV real time PCR quantification. J Virol Methods. Aug 2009;159(2):265-70. [Medline].

 
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Liver biopsy specimen showing the ground-glass appearance of hepatocytes in a patient with hepatitis B.
Liver biopsy with trichrome stain showing stage 3 fibrosis in a patient with hepatitis B.
Liver biopsy with hematoxylin stain showing stage 4 fibrosis (ie, cirrhosis) in a patient with hepatitis B.
 
 
 
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