Hepatitis B

Aka: Hepatitis B, Hepatitis B Virus, Hepadnaviridae Infection, Acute Type B Viral Hepatitis

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II. 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: 254 million infected (2022)
      1. Responsible for 1.1 million deaths in 2022
  3. U.S.
    1. As of 2018, 36% of cases were injection drug related (driven by Opioid epidemic)
    2. Acute Hepatitis B Incidence: 13,000 to 22,000 per year (1.1 per 100,000) in 2015
    3. Chronic Hepatitis BPrevalence: Up to 2.4 million (in 2022)
      1. Responsible for 1,787 deaths in 2022

III. Pathophysiology

  1. Hepadnavirus (Family Hepadnaviridae)
    1. Icosahedral, double-stranded DNA Virus, 42 nm in size
    2. Partially double-stranded DNA
    3. Has 10 Genotypes (A-J) and 30 subtypes
      1. Genotypes A-D are most common in the United States
      2. Each Genotype confers specific treatment responses and complication risks (HCC, Cirrhosis)
    4. HBV is the only DNA, primary Viral Hepatitis
      1. All other primary Viral Hepatitis causes are RNA Viruses (HAV, HCV, HDV, HEV)
  2. Components
    1. Dane particle (entire virus, 42 nm)
      1. Spherical intact virus (envelope, icosahedral capsid enclosing dsDNA)
    2. Antigens
      1. HBsAg: Outer surface coat encases virus (22 nm)
        1. Long surface filamentous structures of old HBV residual envelope and capsid Protein
        2. Antibody to HBV surface Antigen is protective, conferring Immunity
      2. HBcAg: Inner nucleocapsid core encases genome (27 nm)
        1. Antibody to HBV core Antigen is not protective
      3. HBeAg: Circulating peptide encoded by core gene
        1. Soluble, cleavage product of HBV core released during active HBV infection and growth
        2. Marker of active disease and highly infectious state (including a 90% perinatal transmission rate)
    3. Genome
      1. Covalently closed circular dsDNA (cccDNA)
        1. Allows for HBV to persist in the hepatocyte nucleus despite Antiviral therapy
        2. Allows for HBV reactivation during times of Immunosuppression
      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 is 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

IV. Risk Factors

  1. HIV Infection
  2. Hepatitis C Infection
  3. Intravenous Drug Abuse
  4. Sexually Transmitted Disease
  5. Hemodialysis patients
  6. Healthcare workers
  7. Incarceration history
  8. Born to parent with HBsAg positive
  9. Unvaccinated in childhood AND parents from regions with very high HBV Prevalence (>8%)
  10. Hepatic transaminase elevation without known cause
  11. Birthplace in endemic areas with high HBV Prevalence (>2%)
    1. Asia and southeast Asia
    2. Pacific Islands
    3. Eskimo
    4. India
    5. Sub-Sahara Africa
    6. Haiti

V. 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 (10% of patients)

VI. Differential Diagnosis

  1. Acute Hepatitis Causes

VII. Labs: General

  1. Liver Function Tests
    1. Serum transaminases peaks 1-2 weeks before Jaundice
      1. Typically elevated, and often the initial clinical finding that prompts serologic identification
      2. Peak AFTER specific markers (HBV DNA, HBeAg, HBsAg)
      3. Alanine Aminotransferase (ALT)
      4. 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

VIII. Labs: Viral Hepatitis

  1. Viral Hepatitis Screening
    1. Anti-HAV Antibody
    2. Anti-HCV Antibody
    3. Acute Hepatitis B Infection Screening
      1. See Risk Factors above
      2. See Hepatitis B Serology (includes indications for screening)
      3. Screening (Identifies most cases of Acute Hepatitis B)
        1. HBsAg (active HBV infection)
        2. xHBc IgM (or Anti-HBc Antibody, detects HBV exposure)
          1. HBcAb IgM is detected after symptom onset and wane after first 6-9 months
          2. HBcAb IGG develops after IgM and persist for life
        3. HBsAb (for HBV Immunity)
          1. Present after effective Immunization
          2. Adults clear Antigen and develop HBsAb (or HBeAb) in 95% of cases, and within 6-12 months
  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

IX. Management: Prophylaxis of contacts

  1. See Hepatitis B Postexposure Prophylaxis
  2. See Hepatitis B Prophylaxis in Newborns

X. Management: Acute Hepatitis B

  1. Symptomatic management
  2. Antiviral therapy offers no benefit in the acute phase
    1. Contrast with treatment of Chronic Hepatitis B which can prevent Cirrhosis and Hepatocellular Carcinoma
    2. 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

XI. Management: Chronic Hepatitis B

  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

XII. Complications

  1. Fulminant Hepatitis (0.1 to 0.5%, up to 1-4% of Acute Hepatitis B cases)
    1. See Fulminant Hepatitis
    2. Mortality approaches 80% in severe cases
    3. Liver Transplant indication
  2. Chronic Hepatitis B Carrier
  3. Chronic Hepatitis B Infection
    1. See Chronic Hepatitis B Infection
    2. Autoimmune response (cytotoxic T cell)
      1. Hepatotoxic response
      2. Immune complex deposition response in other tissues (e.g. joints, Kidneys)
    3. Subtypes
      1. Chronic persistent Hepatitis B
      2. Chronic active Hepatitis B
      3. Hepatitis DVirus coinfection

XIII. Prognosis: Acute Hepatitis B

  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

XIV. Prevention

  1. Hepatitis B Vaccine
    1. Substantial decrease in U.S. of HBV Incidence since the Vaccine was first introduced in 1982
    2. However, only 30% of U.S. adults Hepatitis B vaccinated, despite Primary Series and indicated in all adults up to 59 years
  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

XV. Resources

  1. CDC NCI Viral Hepatitis B
    1. http://www.cdc.gov/ncidod/diseases/hepatitis/b

XVI. References

  1. Berenguer in Feldman (2002) Sleisenger GI, p. 1285-303
  2. Befeler (2000) Infect Dis Clin North Am 14:617-32 [PubMed]
  3. Lin (2004) Am Fam Physician 69:75-86 [PubMed]
  4. Moore (2026) Am Fam Physician 113(3): 229-34 [PubMed]
  5. Wilkins (2019) Am Fam Physician 99(5): 314-23 [PubMed]

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