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Hepatitis A

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Hepatitis A, Hepatitis A Virus

  • Epidemiology
  1. Endemic in underdeveloped countries
  2. More common in western United States
  3. Outbreaks
    1. Day-care centers
    2. Residential institutions
  4. Incidence
    1. World: 1.4 Million/year
    2. U.S. (esp west): 60,000/year (only 7700 reported)
      1. Decreased >90% following Hepatitis A Vaccine introduction in 1995
  • Pathophysiology
  1. Picornavirus (enterovirus)
    1. Single stranded RNA genome
    2. Size: 27 nm
    3. Nonenveloped (resistant to bile lysis)
    4. Only replicates in hepatocytes, GI epithelial cells
  2. Hardy agent
    1. Resistant to acids, detergents, freezing Temperatures
    2. Survives in salt water and fresh water, soil, hands
    3. Inactivated by heat >185 F, formalin, Chlorine
  • Pathophysiology
  • Timing
  1. Incubation: 15 to 50 days (mean 28 days)
  2. Duration: 2 weeks to 3 months
  3. Contagious status
    1. Infectivity peaks 2 weeks before and 1 week after symptom onset
    2. Stool virus concentration peaks 2 weeks before symptoms
      1. Virus replicates in liver and shed by bilary tract
      2. Stool is highly contagious
      3. Transmission most likely in presymptomatic period
      4. Asymptomatic children may shed virus for months
    3. No longer contagious once significant symptoms occur
      1. Jaundice
      2. Liver transaminase peak
  • Pathophysiology
  • Transmission
  1. Oral-Fecal transmission
    1. Household or child care centers
    2. Sexual contact
  2. Foodborne Illness epidemic
    1. Infected food handlers
    2. Raw shellfish
    3. Fresh produce (green onions, strawberries)
  3. Waterborne Illness epidemic
  4. Blood exposure can occur but is uncommon
  • Symptoms
  1. Symptom occurence depends on age
    1. Adults: 70% have symptoms
    2. Children under age 6: 70% do not have symptoms
      1. Usually more mild in young children
  2. Common symptoms (onset 5-7 days before Jaundice)
    1. Fever
    2. Severe Anorexia out of proportion with clinical signs
    3. Nausea and Vomiting
    4. Abdominal Pain
    5. Malaise
    6. Headache
  3. Other less common symptoms
    1. Arthralgias
    2. Myalgias
    3. Diarrhea
    4. Cough
    5. Constipation
    6. Pruritus
    7. Urticaria
  • Signs
  • Pre-icteric (starting 5-7 days before Jaundice)
  1. Fever
  2. Enlarged and tender liver (Hepatomegaly)
  3. Splenomegaly
  4. Bradycardia
  5. Posterior cervical adenopathy
  • Signs
  • Icteric phase
  1. Pale, clay colored stool
  2. Dark Urine
  3. Jaundice (Incidence increases with age)
    1. Under age 6: <10%
    2. Adults: Up to 80%
  • Course
  1. Illness usually lasts 2 months
  2. Not uncommon to miss 1 month of school or work
  3. Usually complete recovery within 6-12 months
  4. No chronic carrier state
  • Labs
  1. Complete Blood Count (CBC)
    1. Leukopenia
  2. Liver Transaminases elevated
    1. Transaminases are higher than in Alcoholic heptitis and similar or lower than toxic or ischemic hepatitis
    2. Alanine Aminotransferase (ALT) elevated (500 - 5000 U/L)
    3. Aspartate Aminotransferase (AST) elevated (500 - 5000 U/L)
      1. Typically lower than the ALT
  3. Liver Function Tests and Cholestasis Labs elevated
    1. Bilirubin elevated (<10 mg/dl)
      1. Increase typically follows the transaminase increase
    2. Alkaline Phosphatase minimally increased
  1. Fecal HAV: present 2-6 weeks after exposure
  2. xHAV IgM
    1. Present 4-12 weeks (up to 6 months) post-exposure
    2. Present 5-10 days before symptom onset
    3. Preferred first-line test (high Test Sensitivity >95%)
      1. Risk of False Positive in asymptomatic patients
  3. xHAV IgG
    1. Present from 4 weeks after exposure
    2. Present life-long and confers immunity
  • Differential Diagnosis
  • Management
  1. Symptomatic relief
    1. Antiemetics
    2. Avoid Alcohol and other Hepatotoxins
    3. Diet as tolerated otherwise
  2. Rest
    1. Avoid return to work, school until fever and Jaundice resolve
  • Management
  • Post-exposure
  1. Indications
    1. Serologically confirmed case and
    2. Exposure during source patient's incubation period and extending until one week after Jaundice onset
  2. Administer Vaccine or Immunoglobulin within 2 weeks of exposure
  3. Hepatitis A Vaccine (preferred in most cases)
    1. Offer to all outbreak exposures >age 1 years old
    2. Exceptions
      1. Isolated, single case exposures with casual contact (e.g. school, office)
      2. Controlled setting with barrier precautions (e.g. hospital)
  4. Hepatitis A Immunoglobulin (0.02 ml/kg IM) indications
    1. Patient <1 year old
    2. Age over 40 years old
    3. Serious comorbidity
    4. Immunocompromised
    5. Chronic Liver Disease
    6. Severe allergy to Hepatitis A Vaccine
  5. Monitoring
    1. Hepatitis A Virus Antibody testing is optional
  6. References
    1. (2007) MMWR Morb Mortal Wkly Rep 56(41): 1080-4 [PubMed]
  • Prevention
  1. General Hygiene Measures in endemic areas
    1. Meticulous Hand Washing
    2. Clean surfaces with 1:100 solution household bleach
    3. Careful food preparation
      1. See Prevention of Foodborne Illness
      2. Heat foods to 185 F for 1 minute
      3. Avoid uncooked foods
  2. Hepatitis A Vaccine for high risk potential exposures
    1. Protective for 20 years or more after 2 doses
    2. Recommended as part of Primary Series for child age 1 year
  3. Hepatitis A Immunoglobulin
    1. Preexposure for travel within 1 month
    2. Postexposure for close contacts of known case
  • Complications
  1. Most cases follow a benign, self limited course
    1. No increased risk of Cirrhosis and liver cancer
    2. No chronic form of Hepatitis A
  2. Uncommon complications
    1. Relapsing Hepatitis A infection (occurs in up to 15% at up to 6 months after the initial infection)
  3. Rare liver complications
    1. Biliary obstruction
    2. Fulminant Hepatitis (rare)
  4. Rare extra-hepatic complications
    1. Vasculitis
    2. Arthritis
    3. Thrombocytopenia
    4. Acute Pancreatitis
    5. Aplastic or Autoimmune Hemolytic Anemia
    6. Acute Renal Failure
    7. Pericarditis
    8. Guillain-Barre Syndrome
  5. Mortality
    1. Caused 100 U.S. deaths per year prior to routine Hepatitis A Vaccine
  • Prognosis
  • Risk factors for serious complications
  1. Age over 50 years
  2. Underlying liver disease (e.g. Hepatitis B, Hepatitis C)
  3. Pregnancy
  • Resources