Hepatitis A

Aka: Hepatitis A, Hepatitis A Virus

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II. Epidemiology

  1. Endemic in underdeveloped countries
  2. More common in western United States
  3. Outbreaks
    1. Day-care centers
    2. Residential institutions
    3. Unvaccinated population pockets
  4. Incidence
    1. World: 1.4 Million/year
    2. U.S. (esp west): 60,000/year in 1971
      1. Decreased >90% following Hepatitis A Vaccine introduction in 1995, and improved food safety
      2. Reported Cases 1390 to 2007 in U.S. in 2015-16

III. Pathophysiology

  1. Picornavirus (enterovirus)
    1. Single stranded RNA genome (positive strand)
    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

IV. Pathophysiology: Timing

  1. Incubation: 15 to 50 days (mean 28-30 days)
  2. Duration: 2 weeks to 3 months
  3. Contagious status
    1. Infectivity peaks 2 weeks before and 1 week after Jaundice 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
  4. Infectious Course
    1. Ingested stool particles contain Hepatitis A Virus
    2. Hepatitis A Virus is absorbed from Stomach and Small Intestine
    3. Virus reaches the liver via portal circulation
    4. Hepatitis A Virus replicates within hepatocytes
    5. Virus may be detected in blood or stool within 10-12 days after infection
    6. Viral shedding may start 2 weeks before symptom onset
    7. Virus excreted in stool for up to 3 weeks after symptom onset

V. 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 Transfusion exposure can occur but is uncommon

VI. Risk Factors

  1. Illicit Drug Use
  2. International travel to regions with high moderate to high endemic infection rates
  3. Men who have Sex with Men
  4. Homeless
  5. Developmental Disability setting
  6. Incarceration
  7. Occupational exposure to Hepatitis A
  8. Exposure to people at high risk for Hepatitis A (e.g. international adoptee)

VII. Symptoms

  1. Symptom occurence depends on age
    1. Adults: 70% have symptoms
    2. Children under age 6 years: 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
    8. Rash

VIII. Signs

  1. Pre-icteric (starting 5-7 days before Jaundice)
    1. Fever
    2. Enlarged and tender liver (Hepatomegaly)
    3. Splenomegaly
    4. Bradycardia
    5. Posterior cervical adenopathy
  2. Icteric phase
    1. Pale, clay colored stool
    2. Dark Urine
    3. Hepatomegaly (78%)
    4. Jaundice (Incidence increases with age)
      1. Under age 6: <10%
      2. Adults: 40 to 80%

IX. Course

  1. Illness usually lasts 2 months
    1. Not uncommon to miss 1 month of school or work
  2. Delayed recovery over 6 months in 10-15% of cases
  3. Acute Liver Failure in 1% of patients (see complications below)
  4. Liver Function Tests may not fully resolve for 2-3 months
  5. No chronic carrier state

X. 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
  4. Other Testing
    1. Prothrombin Time (INR)
    2. Serum Electrolytes
    3. Serum Glucose
    4. Serum Creatinine
      1. Serum Creatinine >2 mg/dl is a predictor of Fulminant Hepatitis and death

XI. Diagnosis: Hepatitis A Serology

  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

XII. Differential Diagnosis

  1. Acute Hepatitis Causes

XIII. Management: Symptomatic

  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
  3. Precautions
    1. Immediate return for Acute Liver Failure symptoms, signs (e.g. Altered Mental Status)

XIV. 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 and/or Immunoglobulin within 2 weeks of exposure
  3. Hepatitis A Vaccine (preferred in most cases)
    1. Offer to all outbreak exposures >1 year 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
    1. Dose 0.1 ml/kg IM
    2. Provides up to 3 months of protection from Hepatitis A Virus
    3. Risk of Hypersenstivity reaction and increased thrombosis risk
    4. Delay MMR Vaccine and Varicella Vaccine for 6 months after Immunoglobulin
    5. Indications
      1. Patient <1 year old (postexposure, and preexposure in high risk areas)
      2. Age over 40 years old
      3. Serious comorbidity
      4. Immunocompromised
      5. Chronic Liver Disease
      6. Severe allergy to Hepatitis A Vaccine or other contraindication
  5. Monitoring
    1. Hepatitis A Virus Antibody testing is optional
  6. References
    1. (2007) MMWR Morb Mortal Wkly Rep 56(41): 1080-4 [PubMed]

XV. 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. Postexposure for close contacts of known case (see above)
    2. Preexposure for travel to endemic region
      1. Age <6 months OR
      2. Other risk factors listed under pre-exposure as above (e.g. age >40 years, Chronic Liver Disease)
      3. Give with Hepatitis A Vaccine (age >6 months) if travel within next 4 weeks to endemic region

XVI. 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)
    2. Fulminant Hepatitis and Acute Liver Failure (<1% of patients) - some requiring Liver Transplant
      1. Age >40 years
      2. Preexisting liver disease
    3. Biliary obstruction (rare)
  3. Rare extra-hepatic complications
    1. Vasculitis
    2. Reactive Arthritis
    3. Thrombocytopenia
    4. Acute Pancreatitis
    5. Aplastic or Autoimmune Hemolytic Anemia
    6. Acute Renal Failure
    7. Pericarditis
    8. Anemia
    9. Acute Cholecystitis
    10. Guillain-Barre Syndrome
  4. Pregnancy Complications
    1. Preterm contractions and Preterm Labor
    2. Placental Separation
    3. Premature Rupture of Membranes
  5. Mortality
    1. Caused 100 U.S. deaths per year prior to routine Hepatitis A Vaccine

XVII. Prognosis: Risk Factors for Serious Complications

  1. Age over 50 years
  2. Pregnancy
  3. Liver transaminases >2 times normal
  4. HIV Infection
  5. Underlying liver disease
    1. Other Viral Hepatitis (Hepatitis B, Hepatitis C)
    2. Cirrhosis
    3. Autoimmune Hepatitis
    4. Fatty Liver disease

XVIII. Resources

  1. CDC Hepatitis A faq
    1. http://www.cdc.gov/hepatitis/hav/havfaq.htm

XIX. References

  1. Jeong (2010) Intervirology 53(1):15-9 [PubMed]
  2. Langan (2021) Am Fam Physician 104(4): 368-74 [PubMed]
  3. Matheny (2012) Am Fam Physician 86(11): 1027-34 [PubMed]
  4. Yeung (2010) Liver Int 30(1): 5-18 [PubMed]

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