Medscape is available in 5 Language Editions – Choose your Edition here.


Hepatitis A Workup

  • Author: Richard K Gilroy, MBBS, FRACP; Chief Editor: BS Anand, MD  more...
Updated: Jan 28, 2016

Approach Considerations

Nucleic acid testing (NAT) is the gold standard for diagnosis of viremic stages of hepatitis infection.[17]

Central to the prevention of any legal problem is establishing the correct diagnosis, which comes from a combination of careful history and subsequent examination. Appearances may be deceiving; therefore, always exclude drugs, particularly acetaminophen, as a cause of acute liver injury. One of the most common reasons for the misdiagnosis of hepatitis A infection is misinterpretation of the serology tests.

Liver biopsy has a minimal role in acute HAV infection. It may play a part in chronic relapsing HAV infection or in situations where the diagnosis is uncertain. Other investigations (eg, serum acetaminophen) may be necessary, depending on findings from the history and clinical examination. Molecular diagnostic techniques performed on blood and feces for HAV RNA are purely research tools at present.

Kodani et al have developed an NAT-based assay that may be able to detect five viral genomes of hepatitis simultaneously: HAV RNA, HBV DNA, HCV RNA, HDV RNA, and HEV RNA,[17] Independent validation would have potential clinical implications for wider patient surveillance, donor specimens screening, and use in the setting of outbreaks.[17]

After establishing a diagnosis of hepatitis A virus (HAV) infection, tracing contacts and notifying local public health authorities are important steps for preventing further cases. Omitting these measures may place the practitioner in a vulnerable situation.


Complete Blood Count and Coagulation Study

Complete blood count

Mild lymphocytosis is not uncommon. Pure red cell aplasia and pancytopenia may rarely accompany infection. Indices of low-grade hemolysis are not uncommon.

Prothrombin time

The prothrombin time (PT) usually remains within or near the reference range. Significant rises should raise concern and support closer monitoring. In the presence of encephalopathy, an elevated PT has ominous implications (eg, fulminant hepatic failure [FHF]).


Liver Function Tests

Liver enzymes

Rises in the levels of ALT and aspartate aminotransferase (AST) are sensitive for hepatitis A. Levels may exceed 10,000 mIU/mL, with ALT levels generally greater than AST levels. These levels usually return to reference ranges over 5-20 weeks.

Rises in alkaline phosphatase accompany the acute disease and may progress during the cholestatic phase of the illness following the rises in transaminase levels.

Hepatic synthetic function

Bilirubin level rises soon after the onset of bilirubinuria and follows rises in ALT and AST levels. Levels may be impressively high and can remain elevated for several months; persistence beyond 3 months indicates cholestatic HAV infection.

Older individuals have higher bilirubin levels. Both direct and indirect fractions increase because of hemolysis, which often occurs in acute HAV infection.

Modest falls in serum albumin level may accompany the illness.


Serologic Tests

Anti-hepatitis A virus immunoglobulin M

The diagnosis of acute HAV infection is based on serologic testing for immunoglobulin M (IgM) antibody to HAV. Test results for anti-HAV IgM are positive at the time of onset of symptoms and usually accompany the first rise in the alanine aminotransferase (ALT) level.

This test is sensitive and specific, and the results remain positive for 3-6 months after the primary infection and for as long as 12 months in 25% of patients. In patients with relapsing hepatitis, IgM persists for the duration of this pattern of disease. False-positive results are uncommon and should be considered in the event that anti-HAV IgM persists.

Anti-hepatitis A virus immunoglobulin G

Anti-HAV immunoglobulin G (IgG) appears soon after IgM and generally persists for many years. The presence of anti-HAV IgG in the absence of IgM indicates past infection or vaccination rather than acute infection. IgG provides protective immunity.



Imaging studies are usually not indicated in HAV infection. However, ultrasonography may be required when alternative diagnoses must be excluded. The goals should be to assess vessel patency and to evaluate any evidence supporting the presence of unsuspected underlying chronic liver disease. Ultrasound scanning is essential in patients with FHF.


Histologic Findings

Histopathology reveals pronounced portal inflammation early in the illness, which is consistent with viral hepatitis. Focal necrosis and acidophilic bodies are less pronounced than infections with hepatitis B virus (HBV) and hepatitis C virus (HCV).

In FHF, biopsy findings may show extensive cell loss with ballooning in many of the remaining hepatocytes. Immunofluorescent stains for HAV antigen yield positive results.

Contributor Information and Disclosures

Richard K Gilroy, MBBS, FRACP Associate Professor, Medical Director of Liver Transplantation and Hepatology, Department of Internal Medicine, Kansas University Medical Center

Disclosure: Received salary from gilead, NPS pharmaceuticals, salix pharmaceuticals, AbbVie for speaking and teaching.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Additional Contributors

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, Association of American Physicians

Disclosure: Received consulting fee from Springer for consulting; Received consulting fee from Gilead for review panel membership; Received honoraria from Vertex for speaking and teaching; Received honoraria from Bristol-Myers Squibb for speaking and teaching; Received royalty from Springer for review panel membership; Received honoraria from Merck for speaking and teaching.


Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

  1. Longatti A. The dual role of exosomes in hepatitis A and C virus transmission and viral immune activation. Viruses. 2015 Dec 17. 7(12):6707-15. [Medline].

  2. Liu W, Zhai J, Liu J, Xie Y. Identification of recombination between subgenotypes IA and IB of hepatitis A virus. Virus Genes. 2010 Apr. 40(2):222-4. [Medline].

  3. Kaplan G, Totsuka A, Thompson P, et al. Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus. EMBO J. 1996 Aug 15. 15(16):4282-96. [Medline].

  4. Wheeler C, Vogt TM, Armstrong GL, et al. An outbreak of hepatitis A associated with green onions. N Engl J Med. 2005 Sep 1. 353(9):890-7. [Medline].

  5. Wasley A, Grytdal S, Gallagher K, Centers for Disease Control and Prevention (CDC). Surveillance for acute viral hepatitis--United States, 2006. MMWR Surveill Summ. 2008 Mar 21. 57(2):1-24. [Medline].

  6. Ansaldi F, Bruzzone B, Rota MC, et al. Hepatitis A incidence and hospital-based seroprevalence in Italy: a nation-wide study. Eur J Epidemiol. 2008. 23(1):45-53. [Medline].

  7. Dominguez A, Bruguera M, Plans P, et al. Declining hepatitis A seroprevalence in adults in Catalonia (Spain): a population-based study. BMC Infect Dis. 2007. 7:73. [Medline].

  8. Aggarwal R, Goel A. Hepatitis A: epidemiology in resource-poor countries. Curr Opin Infect Dis. 2015 Oct. 28(5):488-96. [Medline].

  9. Kanyenda TJ, Abdullahi LH, Hussey GD, Kagina BM. Epidemiology of hepatitis A virus in Africa among persons aged 1-10 years: a systematic review protocol. Syst Rev. 2015 Sep 26. 4:129. [Medline].

  10. Chobe LP, Arankalle VA. Investigation of a hepatitis A outbreak from Shimla Himachal Pradesh. Indian J Med Res. 2009 Aug. 130(2):179-84. [Medline].

  11. Cao J, Wang Y, Song H, et al. Hepatitis A outbreaks in China during 2006: application of molecular epidemiology. Hepatol Int. 2009 Jun. 3(2):356-63. [Medline]. [Full Text].

  12. Kamath SR, Sathiyasekaran M, Raja TE, Sudha L. Profile of viral hepatitis A in Chennai. Indian Pediatr. 2009 Jul. 46(7):642-3. [Medline].

  13. Fischer GE, Thompson N, Chaves SS, et al. The epidemiology of hepatitis A virus infections in four Pacific Island nations, 1995-2008. Trans R Soc Trop Med Hyg. 2009 Sep. 103(9):906-10. [Medline].

  14. Amin J, Gilbert GL, Escott RG, et al. Hepatitis A epidemiology in Australia: national seroprevalence and notifications. Med J Aust. 2001 Apr 2. 174(7):338-41. [Medline].

  15. Cooksley WG. What did we learn from the Shanghai hepatitis A epidemic?. J Viral Hepat. 2000 May. 7 Suppl 1:1-3. [Medline].

  16. Mofenson LM, Brady MT, Danner SP, et al. Guidelines for the prevention and treatment of opportunistic infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep. 2009 Sep 4. 58:1-166. [Medline]. [Full Text].

  17. Kodani M, Mixson-Hayden T, Drobeniuc J, Kamili S. Rapid and sensitive approach to simultaneous detection of genomes of hepatitis A, B, C, D and E viruses. J Clin Virol. 2014 Oct. 61(2):260-4. [Medline].

  18. Worns MA, Teufel A, Kanzler S, et al. Incidence of HAV and HBV infections and vaccination rates in patients with autoimmune liver diseases. Am J Gastroenterol. 2008 Jan. 103(1):138-46. [Medline].

  19. Kanda T, Nakamoto S, Wu S, et al. Direct-acting antivirals and host-targeting agents against the hepatitis A virus. J Clin Transl Hepatol. 2015 Sep 28. 3(3):205-10. [Medline].

  20. Jacobsen K, Wierman S. Hepatitis A virus seroprevalence by age and world region. 1990-2005. Vaccine. 2010. 28(41):6653-6657.

  21. Jacobsen KH, Koopman JS. Declining hepatitis A seroprevalence: a global review and analysis. Epidemiol Infect. 2004 Dec. 132(6):1005-22. [Medline]. [Full Text].

  22. Klevens RM, Miller JT, Iqbal K, et al. The evolving epidemiology of hepatitis a in the United States: incidence and molecular epidemiology from population-based surveillance, 2005-2007. Arch Intern Med. 2010 Nov 8. 170(20):1811-8. [Medline].

  23. Costas L, Vilella A, Trilla A, et al. Vaccination strategies against hepatitis A in travelers older than 40 years: an economic evaluation. J Travel Med. 2009 Sep-Oct. 16(5):344-8. [Medline].

  24. Marano C, Freedman DO. Global health surveillance and travelers' health. Curr Opin Infect Dis. 2009 Oct. 22(5):423-9. [Medline].

  25. Askling HH, Rombo L, Andersson Y, Martin S, Ekdahl K. Hepatitis A risk in travelers. J Travel Med. 2009 Jul-Aug. 16(4):233-8. [Medline].

  26. Centers for Disease Control and Prevention (CDC). National, state, and local area vaccination coverage among children aged 19-35 months - United States, 2008. MMWR Morb Mortal Wkly Rep. 2009 Aug 28. 58(33):921-6. [Medline].

  27. Centers for Disease Control and Prevention (CDC). Hepatitis a vaccination coverage among children aged 24-35 months - United States, 2006 and 2007. MMWR Morb Mortal Wkly Rep. 2009 Jul 3. 58(25):689-94. [Medline].

  28. Irving GJ, Holden J, Yang R, Pope D. Hepatitis A immunisation in persons not previously exposed to hepatitis A. Cochrane Database Syst Rev. 2012 Jul 11. 7:CD009051. [Medline].

  29. Petrignani M, Verhoef L, Vennema H, et al. Underdiagnosis of foodborne hepatitis A, The Netherlands, 2008-2010(1.). Emerg Infect Dis. 2014 Apr. 20 (4):596-602. [Medline].

Hepatitis A virus as viewed through electron microscopy.
Hepatitis A. Time course of infection.
Hepatitis A.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.