Hepatitis A Virus - HAV

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.

Tabs Content

Clinical Overview

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

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 Lab Tests

Evaluate viral etiology in patients with acute hepatitis

Not recommended for screening asymptomatic patients

Panel includes HAV IgM, HBV core antibody IgM, HBV surface antigen, HCV antibody

Hepatitis Panel, Acute with Reflex to HBsAg Confirmation 0020457

Method: Qualitative Chemiluminescent Immunoassay

Reflex pattern: if results for HBsAg are repeatedly reactive with an index value between 1.00 and 50.00, then HBsAg confirmation testing will be added

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

Hepatitis A Virus Antibody, IgM 0020093

Method: 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

Hepatitis A Virus Antibodies (Total) 0020591

Method: Qualitative Chemiluminescent Immunoassay

Initial screening for hepatobiliary inflammation

Hepatic Function Panel 0020416

Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Panel includes albumin; alkaline phosphatase (ALP); aspartate aminotransferase (AST); alanine aminotransferase (ALT); bilirubin, direct; protein, total; and bilirubin, total

Related Tests

Identify infectious processes

CBC with Platelet Count and Automated Differential 0040003

Method: Automated Cell Count/Differential

Panel is not recommended

Order hepatitis A virus IgM antibody to diagnose acute infection

Order HAV total for assessing immunity

Hepatitis A Virus Panel 0020597

Method: Qualitative Chemiluminescent Immunoassay

Medical Experts

Genzen, Jonathan R., MD, PhD, Chief Operations Officer, Medical Director of Automated Core Laboratory and Farmington Health Center Clinical Laboratory, at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Lehman, Christopher M., MD, Co-Medical Director, University Hospitals and Clinics Clinical Laboratory; Professor of Clinical Pathology, University of Utah

Slev, Patricia R., PhD, Section Chief, Immunology; Medical Director, Serologic Hepatitis and Retrovirus and Immunology Core Laboratory; Co-Medical Director, Microbial Immunology, at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

References

Guidelines

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases - Hepatitis A. Centers for Disease Control and Prevention. Atlanta, GA [Last updated: May 2015; Accessed: Aug 2017]
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2015. June 5, 2015, 64(RR3);1-137. Centers for Disease Control and Prevention. Atlanta, GA [Last updated: Jun 2015; Accessed: Aug 2017]
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. Centers for Disease Control and Prevention: Morbidity and Mortality Weekly Report. Atlanta, GA [Published: Sep 2009; Accessed: Aug 2017]
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). Centers for Disease Control and Prevention: Morbidity and Mortality Weekly Report. Atlanta, GA [Published: Oct 2007; Accessed: Aug 2017]
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Prevention of Hepatitis A Through Active or Passive Immunization - Recommendations of the Advisory Committee on Immunization Practices (ACIP). Centers for Disease Control and Prevention: Morbidity and Mortality Weekly Report. Atlanta, GA [Published: May 2006; Accessed: April 2019]
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedule for Adults Aged 19 Years or Older. United States 2019. Center for Disease Control and Prevention. [Last updated: Feb 2019; Accessed: Sep 2019]
Centers for Disease Control and Prevention. Manual for the Surveillance of Vaccine-Preventable Diseases. Centers for Disease Control and Prevention. Atlanta, GA [Updated: Apr 2018; Accessed: Jul 2019]
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger. United States, 2019. Centers for Disease Control and Prevention. Atlanta, GA [Last updated: Feb 2019; Accessed: Sep 2019]

General References

Andersson KL, Friedman LS. Hepatitis a: a traveling target; comment on "the evolving epidemiology of hepatitis a in the United States". Arch Intern Med. 2010; 170(20): 1818-9. PubMed

Jeong S, Lee H. Hepatitis A: clinical manifestations and management. Intervirology. 2010; 53(1): 15-9. PubMed

Kojaoghlanian T. Hepatitis A. Pediatr Rev. 2010; 31(8): 348-50. PubMed

Matheny SC, Kingery JE. Hepatitis A. Am Fam Physician. 2012; 86(11): 1027-34; quiz 1010-2. PubMed

Nainan OV, Xia G, Vaughan G, Margolis HS. Diagnosis of hepatitis a virus infection: a molecular approach. Clin Microbiol Rev. 2006; 19(1): 63-79. PubMed

Sharapov UM, Hu DJ. Viral hepatitis A, B, and C: grown-up issues. Adolesc Med State Art Rev. 2010; 21(2): 265-86, ix. PubMed

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Viral Hepatitis - Hepatitis A Information. Centers for Disease Control and Prevention. [Accessed: Aug 2017]

Testing Algorithms

Hepatitis Virus Screening Algorithm

Read more about Hepatitis Virus Screening Algorithm

Educational Videos

Last Update: October 2019

Hepatitis A Virus - HAV

Diagnosis

Indications for Testing

Laboratory Testing

Differential Diagnosis

Background

Epidemiology

Organism

Risk Factors

Clinical Presentation

Prevention

Background

Epidemiology

Organism

Risk Factors

Clinical Presentation

Prevention

ARUP Lab Tests

Medical Experts

References

Guidelines

General References

Hepatitis Virus Screening Algorithm

ARUP Laboratories

ARUP Websites

ARUP Consult


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Hepatitis A Virus - HAV

Diagnosis

Indications for Testing

Laboratory Testing

Differential Diagnosis

Background

Epidemiology

Organism

Risk Factors

Clinical Presentation

Prevention

Background

Epidemiology

Organism

Risk Factors

Clinical Presentation

Prevention

ARUP Lab Tests

Medical Experts

References

Guidelines

General References

Hepatitis Virus Screening Algorithm

ARUP Laboratories

ARUP Websites

ARUP Consult