Approach Considerations
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.
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.
One important note is that the most common reason for misdiagnosis of hepatitis A is misinterpreting the serology tests.
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]).
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.
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. 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.
Ultrasonography
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.
Other 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.
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 with infections of 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.
Liu W, Zhai J, Liu J, Xie Y. Identification of recombination between subgenotypes IA and IB of hepatitis A virus. Virus Genes. Dec 12 2009;epub ahead of print. [Medline].
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. Aug 15 1996;15(16):4282-96. [Medline].
Wheeler C, Vogt TM, Armstrong GL, et al. An outbreak of hepatitis A associated with green onions. N Engl J Med. Sep 1 2005;353(9):890-7. [Medline].
Wasley A, Grytdal S, Gallagher K,. Surveillance for acute viral hepatitis--United States, 2006. MMWR Surveill Summ. Mar 21 2008;57(2):1-24. [Medline].
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].
Domínguez 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].
Chobe LP, Arankalle VA. Investigation of a hepatitis A outbreak from Shimla Himachal Pradesh. Indian J Med Res. Aug 2009;130(2):179-84. [Medline].
Cao J, Wang Y, Song H, Meng Q, Sheng L, Bian T, et al. Hepatitis A outbreaks in China during 2006: application of molecular epidemiology. Hepatol Int. Jun 2009;3(2):356-63. [Medline].
Kamath SR, Sathiyasekaran M, Raja TE, Sudha L. Profile of viral hepatitis A in Chennai. Indian Pediatr. Jul 2009;46(7):642-3. [Medline].
Fischer GE, Thompson N, Chaves SS, Bower W, Goldstein S, Armstrong G, et al. The epidemiology of hepatitis A virus infections in four Pacific Island nations, 1995-2008. Trans R Soc Trop Med Hyg. Sep 2009;103(9):906-10. [Medline].
Amin J, Gilbert GL, Escott RG, et al. Hepatitis A epidemiology in Australia: national seroprevalence and notifications. Med J Aust. Apr 2 2001;174(7):338-41. [Medline].
Cooksley WG. What did we learn from the Shanghai hepatitis A epidemic?. J Viral Hepat. May 2000;7 Suppl 1:1-3. [Medline].
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. Sep 4 2009;58:1-166. [Medline].
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. Jan 2008;103(1):138-46. [Medline].
Jacobsen K, Wierman S. Hepatitis A virus seroprevalence by age and world region. 1990-2005. Vaccine. 2010;28(41):6653-6657.
Jacobsen KH, Koopman JS. Declining hepatitis A seroprevalence: a global review and analysis. Epidemiol Infect. Dec 2004;132(6):1005-22. [Medline]. [Full Text].
Klevens RM, Miller JT, Iqbal K, Thomas A, Rizzo EM, Hanson H, 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. Nov 8 2010;170(20):1811-8. [Medline].
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. Sep-Oct 2009;16(5):344-8. [Medline].
Marano C, Freedman DO. Global health surveillance and travelers' health. Curr Opin Infect Dis. Oct 2009;22(5):423-9. [Medline].
Askling HH, Rombo L, Andersson Y, Martin S, Ekdahl K. Hepatitis A risk in travelers. J Travel Med. Jul-Aug 2009;16(4):233-8. [Medline].
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. Aug 28 2009;58(33):921-6. [Medline].
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. Jul 3 2009;58(25):689-94. [Medline].

