Hepatitis A Workup

Updated: May 08, 2019
  • Author: Richard K Gilroy, MD, FRACP; Chief Editor: BS Anand, MD  more...
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Approach Considerations

Nucleic acid testing (NAT) is the gold standard for the 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 the diagnosis acute of 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 the 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 its 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 the 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 seen in 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.