Hepatitis A virus (HAV) is the most common cause of viral hepatitis worldwide. However, the targeted use of the HAV vaccine in the U.S. since 1995 has led to a 92% decrease in the number of reported cases. Testing for acute hepatitis by panel allows for identification of viral etiology.
Quick Answers for Clinicians
Diagnosis
Indications for Testing
- New onset of jaundice, anorexia, dark urine, abdominal pain
- Hepatomegaly, splenomegaly, bradycardia, lymphadenopathy, elevated transaminase levels
- Suspected exposure to hepatitis A virus (HAV)
Laboratory Testing
- HAV information for health professionals (CDC, 2015)
- HAV case definition and classification (CDC, 2012)
- Initial testing (nonspecific)
- CBC – usually normal
- Transaminases – usually markedly elevated
- Testing for acute hepatitis
- Identify viral etiology
- Hepatitis acute panel includes HAV, hepatitis B, and hepatitis C
- HAV IgM antibodies
- Diagnose acute HAV infection if exposure is suspected or documented
- Antibodies generally appear 4 weeks after infection (~5 days before symptoms)
- May persist up to 6 months after onset of clinical symptoms
- Total HAV antibodies (IgM and IgG)
- Assess immunity for HAV from vaccination or previous infection (presence of antibodies is associated with immunity)
- IgG does not appear until convalescent phase but remains detectable for life
- Refer to Immunization Status topic for more information
Differential Diagnosis
- Virus
- Hepatitis B, C, D, or E
- Cytomegalovirus
- Epstein-Barr virus
- Herpes simplex virus
- Varicella-zoster virus
- Toxin exposure
- Alcohol
- Tetrachloride
- Nonalcoholic acute steatohepatitis
- Drug-induced hepatitis
- Acetaminophen
- Antiseizure medications
- Isoniazid (Nydrazid)
- Oral contraceptives
- Rifampin (Rifadin)
- Sulfonamides
- Autoimmune disease
- Systemic lupus erythematosus
- Primary biliary cirrhosis
- Sclerosing cholangitis
- Autoimmune hepatitis
- Bacterial infection
- Leptospira spp
- Coxiella burnetii (Q-fever)
- Rickettsia rickettsii (Rocky Mountain spotted fever)
- Treponema pallidum (secondary syphilis)
- Sepsis
- Rickettsia typhi (typhus fever)
- Granulomatous disease
- Mycobacterium tuberculosis
- Sarcoidosis
- Hereditary disease/disorder
- Ischemia
- Parasitic infection
- Liver trematodes
- Toxocara spp
Background
Epidemiology
- Incidence – 1/100,000
- Most common cause of viral hepatitis worldwide
- 2,000 cases in the U.S. in 2009 (CDC)
- 50-70% of U.S. adults have antibodies
- Age – more prevalent among daycare and school-aged children
- Transmission
- Fecal-oral (unlike hepatitis B [HBV] or hepatitis C [HCV])
- Ingestion of contaminated food or water
- Occurs sporadically or in epidemics
- Virus only viable on fomites, including produce, for about 1 week
- Viral shedding in the stool lasts up to 6 months, but period of greatest contagiousness is the 2 weeks prior to onset of jaundice
Organism
- Nonenveloped RNA picornavirus
- Infects only primates
- Survives for extended periods in seawater, fresh water, waste water, and soil
- Resistant to freezing, detergents, and acids
- Resistant to bile lysis due to lack of lipid envelope
- Infects hepatocytes – no propensity for chronic infection
Risk Factors
- Raw seafood
- Infected food handlers
- Daycare settings
- International travel – accounts for ~50% of cases
- No specific risk factors found in 70% of U.S. patients
Clinical Presentation
- Usually asymptomatic or with mild symptoms after incubation period of ~28 days
- Symptoms include fever, nausea, malaise, jaundice, dark urine, abdominal pain, anorexia
- Symptoms last an average of 2 months
- Signs include hepatomegaly, splenomegaly, bradycardia, lymphadenopathy, elevated transaminase levels
- No chronic hepatitis sequelae
- Complications – range from asymptomatic to acute, debilitating disease
- Encephalopathy and fulminant liver failure in patients with immunosuppression or multiple comorbidities (eg, chronic liver or renal disease)
- Gastrointestinal – acalculous cholecystitis, pancreatitis, prolonged cholestasis
- Hematologic – aplastic anemia, autoimmune hemolytic anemia, thrombocytopenic purpura, red cell aplasia
- Neurologic – Guillain-Barré syndrome, mononeuritis, transverse myelitis
- Renal – acute tubular necrosis, interstitial nephritis, glomerulonephritis
- Other – cutaneous vasculitis, cryoglobulinemia, reactive arthritis, pleural or pericardial effusion
- Case fatality rate for HAV infection
- 0.3-0.6% overall
- As high as 1.8% among persons >50 years
- May be prolonged with HIV coinfection
- Significant liver disease is more likely to result in patients with coinfection of HBV or HCV or in pregnant women
Prevention
- Universal vaccination against HAV recommended for
- Children 1-18 years
- High-risk groups, including men who have sex with men, drug abusers, and people who frequently travel to countries endemic for the virus
- Strong immunity results even from relatively low vaccination rates
- Vaccination is recommended prior to school entry or travel to endemic areas
- After vaccination, immunity is active within ~1 week and therefore vaccination is useful as postexposure prophylaxis if given within 2 weeks of exposure
- Vaccination is useful in event of community outbreak
- Intramuscular IgG from pooled human plasma after exposure provides passive protection for ~6 months
ARUP Laboratory Tests
Preferred panel to evaluate viral etiology in patients with acute hepatitis
Not recommended for screening asymptomatic patients
Qualitative Chemiluminescent Immunoassay/Quantitative Transcription Mediated Amplification
Evaluate viral etiology in patients with acute hepatitis
Not recommended for screening asymptomatic patients
Qualitative Chemiluminescent Immunoassay
Components: HAV IgM, HBV core antibody IgM, HBV surface antigen with reflex to confirmation, and HCV antibody
Diagnose acute HAV infection if exposure suspected or documented
For panel test that includes HAV IgM, HBV core antibody IgM, HBV surface antigen, and HCV antibody, refer to acute hepatitis panel with reflex to HBV confirmation
Qualitative Chemiluminescent Immunoassay
May be helpful when assessing immunity
Not generally recommended to diagnose acute infection
Assay detects both IgG and IgM antibodies but does not differentiate between them
Qualitative Chemiluminescent Immunoassay
Initial screening for hepatobiliary inflammation
Quantitative Enzymatic/Quantitative Spectrophotometry
Panel includes albumin; alkaline phosphatase (ALP); aspartate aminotransferase (AST); alanine aminotransferase (ALT); bilirubin, direct; protein, total; and bilirubin, total
Identify infectious processes
Automated Cell Count/Differential
Panel is not recommended
Order hepatitis A virus IgM antibody to diagnose acute infection
Order HAV total for assessing immunity
Qualitative Chemiluminescent Immunoassay
Medical Experts
Genzen

Lehman

Slev

References
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CDC - Manual for the Surveillance of Vaccine-Preventable Diseases - Chapters
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Manual for the surveillance of vaccine-preventable diseases. [Updated: Jun 2020; Accessed: Mar 2021]
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CDC - Epidemiology and Prevention of Vaccine-Preventable Diseases - Hepatitis A
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases: hepatitis A. [Last reviewed: Apr 2019; Accessed: Feb 2020]
CDC MMWR - Prevention of Hepatitis A Through Active or Passive Immunization
Fiore AE, Wasley A, Gell, BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. [Last reviewed: May 2006; Accessed: Feb 2020]
CDC - Adult Immunization Schedule
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Recommended adult immunization schedule for ages 19 years or older, United States, 2020. [Last updated: Feb 2019; Accessed: Sep 2020]
CDC - Recommended Immunization Schedules for Children and Adolescents Aged 18 Years or Younger
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices recommended immunization schedule for children and adolescents aged 18 years or younger – United States, 2019. [Last updated: Feb 2019; Accessed: Sep 2020]
CDC MMWR - Sexually Transmitted Diseases Treatment Guidelines, 2015
Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. Department of Health and Human Services, Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report (MMWR). [Posted: Jun 2015; Accessed: Jan 2021]
CDC - Updated Recommendations from the Advisory Committee on Immunization Practices (ACIP) for Use of Hepatitis A
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Updated recommendations from the advisory committee on immunization practices (ACIP) for use of hepatitis A vaccine in close contacts of newly arriving international adoptees. Morbidity and Mortality Weekly Report. [Last reviewed: Sep 2009; Accessed: Feb 2020]
CDC MMWR - Update: Prevention of Hepatitis A After Exposure to Hepatitis A Virus and in International Travelers
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Update: prevention of hepatitis A after exposure to hepatitis A virus and in international travelers. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report. [Last reviewed: Oct 2007; Accessed: Feb 2020]
CDC - Viral Hepatitis - Hepatitis A Information
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Viral hepatitis - hepatitis A information. [Accessed: Aug 2017]
Components: HAV IgM, HBV core antibody IgM, HBV surface antigen with reflex to confirmation, and HCV antibody with reflex to HCV by quantitative NAAT