Hepatitis A Virus - HAV

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
  • Wilson disease
  • Hemochromatosis
  • Alpha-1-antitrypsin deficiency
• 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