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Hepatitis B

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Hepatitis B, Hepadnaviridae Infection, Acute Type B Viral Hepatitis

  • Epidemiology
  1. Transmission (100 fold more infectious than HIV)
    1. Percutaneous (needlestick) exposure
      1. Sharing non-sterile needles
      2. Tattooing
      3. Health care accidents
    2. Blood product exposure
    3. Sexual contact
    4. Perinatal exposure
  2. Worldwide
    1. Endemic in sub-Saharan Africa, China, Southeast Asia
      1. Acquired in early life in endemic areas
      2. Chronic Hepatitis BPrevalence: 5 to 20%
    2. Worldwide Prevalence: 300 million infected
  3. U.S.
    1. Acute Hepatitis B Incidence: 21,900 per year (1.1 per 100,000) in 2015
    2. Chronic Hepatitis BPrevalence: 850,000 to 2.2 million
  • Pathophysiology
  1. Hepadnavirus (DNA Virus, 42 nm in size)
    1. Family: Hepadnaviridae
    2. Partially double-stranded DNA
    3. Has 10 Genotypes (A-J) and 30 subtypes
  2. Components
    1. Dane particle (entire virus)
    2. Antigens
      1. HBsAg: Outer surface coat encases virus
      2. HBcAg: Inner nucleocapsid core encases genome
      3. HBeAg: Circulating peptide encoded by core gene
    3. Genome
      1. Covalently closed circular dsDNA (cccDNA)
        1. Allows for HBV to persist in the hepatocyte nucleus despite antiviral therapy
      2. DNA polymerase (reverse transcriptase)
        1. Required for virus replication
  3. Hardy infectious agent
    1. Stable after 15 years storage at -20 C
    2. Stable on dried glass at room Temperature for 4 weeks
    3. Stable for 4 hours at 60 C
    4. Stable after exposure to antiseptics
      1. Ultraviolet Radiation
      2. Benzalkonium chloride
      3. Alcohol
    5. Inactivated by a few agents
      1. Glutaraldehyde
      2. Formalin
      3. Urea
  4. Hepatitis B Virus present in blood and body secretions
    1. Saliva
    2. Tears
    3. Vaginal secretions
    4. Breast Milk
  5. Timing
    1. Incubation: 60 to 90 days on average
  • Risk Factors
  1. HIV Infection
  2. Intravenous Drug Abuse
  3. Sexually Transmitted Disease
  4. Hemodialysis patients
  5. Healthcare workers
  6. Travel from endemic areas
    1. Asia and southeast Asia
    2. Pacific Islands
    3. Eskimo
    4. India
    5. Sub-Sahara Africa
    6. Haiti
  • Findings
  • Signs and Symptoms
  1. See Viral Hepatitis
  2. Incidence of symptoms (subclinical in most cases)
    1. Age <5 years: <10%
    2. Age >5 years: 30-50%
  3. Symptoms
    1. Initial Acute Hepatitis B infection
      1. Nausea
      2. Vomiting
      3. Anorexia
      4. Fatigue (may persist)
      5. Headache
      6. Malaise
      7. Low grade fever
      8. Diarrhea
      9. Right Upper Quadrant Abdominal Pain
      10. Myalgia or Arthralgias
      11. Urticaria may also occur
    2. Later Acute Hepatitis B infection
      1. Jaundice
  • Differential Diagnosis
  1. Liver Function Tests
    1. Serum transaminases peaks 1-2 weeks before Jaundice
      1. Alanine Aminotransferase (ALT)
      2. Aspartate Aminotransferase (AST)
    2. Serum Bilirubin (rarely exceeds 20 mg/dl)
      1. Increases after serum transaminases increase
    3. Serum Albumin
      1. Decreased in severe liver disease
    4. Prothrombin Time (with INR)
      1. Increased in severe liver disease
  2. Complete Blood Count
    1. Anemia
    2. Lymphocytosis
  3. Evaluation for complications in high risk patients
    1. See Chronic Hepatitis B
  1. Viral Hepatitis Screening
    1. Anti-HAV Antibody
    2. Anti-HCV Antibody
    3. Acute Hepatitis B Infection Screening
      1. See Hepatitis B Serology (includes indications for screening)
      2. Screening (Identifies most cases of Acute Hepatitis B)
        1. HBsAg
        2. xHBc IgM
  2. Evaluation of positive Hepatitis B Screening
    1. See Hepatitis B Serology (see for stages of Hepatitis B infection)
    2. Additional Hepatitis B Serology
      1. xHBs IgG (test for immunity)
      2. Anti-HBc Antibody
      3. HBeAg
      4. Anti-HBe Antibody
      5. HBV DNA
  3. Comorbid infection
    1. Anti-HDV Antibody
    2. HIV Test
  1. Symptomatic management
  2. Antiviral therapy offers no benefit in the acute phase
    1. Mantzoukis (2017) Cochrane Database Syst Rev (3): CD011645 [PubMed]
  3. Hepatitis B spontaneously resolves in 90% of adults within 3-6 months
    1. Recheck HBsAg at 6 months
  1. Definition: HBsAg positive at 6 months (10%)
  2. Management per Chronic Hepatitis B type
    1. Chronic Hepatitis B Infection
    2. Chronic Hepatitis B Carrier
  • Complications
  1. Outcome in adults and children over age 5 years
    1. Recovery: 90%
    2. Chronic Active Hepatitis: 10%
    3. Fulminant Hepatitis: <1% (high mortality)
    4. Premature death (Hepatocellular Carcinoma, Cirrhosis) from Chronic Hepatitis B in 25% children, 15% adults
  2. Outcome in children under age 5 years
    1. Chronic infection: 30-90%
    2. Younger ages are associated with the highest risk of Chronic Hepatitis B
      1. Trepo (2014) Lancet 384(9959):2053-63 [PubMed]
  3. Worse prognosis if Hepatitis D also present
    1. Cirrhosis higher risk
    2. Hepatocellular Carcinoma higher risk
  • Prevention
  1. Hepatitis B Vaccine
  2. Perinatal Exposure
    1. See Hepatitis B Postexposure Prophylaxis in Newborns
  3. Bloodborne Pathogen Exposure
    1. See Hepatitis B Postexposure Prophylaxis
  4. Reactivation of Hepatitis B
    1. More common now with broadening use of tnf agents (e.g. Rheumatoid Arthritis, Crohn's Disease)
    2. Screen for Hepatitis B (HBsAg, HBcAb) before starting tnf agents or Chemotherapy