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Hepatitis B Serology

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Hepatitis B Serology, Hepatitis B Surface Antibody, Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis B Envelope Antigen, Hepatitis B Envelope Antibody, HBsAg, HBeAg, xHBsAb, xHBs IgG, xHBcAb, xHBc IgM, xHBc IgG, xHBeAb, xHBe IgM, xHBe IgG, Hepatitis B Screening, Hepatitis B Antigen, Hepatitis B Virus Test, Hepatitis B Antibody

  • Indications
  1. Universal screening for U.S. Adults is recommended as of 2023
    1. Triple Screen (HBsAg, HBsAb, HBcAb) at least once in all adults regardless of risk factors
    2. Conners (2023) MMWR Recomm Rep 72(1):1-25 +PMID: 36893044 [PubMed]
  2. Risk Factor Based Screening
    1. Pregnant women at first Prenatal Visit
    2. HIV Positive patients
    3. IV Drug Abuse
    4. Men who have Sex with Men
    5. Household contacts or sexual partners of infected persons
    6. People born in countries with high Prevalence of Hepatitis B Infection (2% or greater Prevalence per CDC)
    7. U.S. born children (but not HepB vaccinated) to parents from countries with Prevalence of Hepatitis B Infection (>8%)
    8. Donors of plasma, organs, tissue or semen
    9. Infants born to mothers who are HBsAg positive
    10. Patients on Hemodialysis or cytotoxic or immunosuppressive therapy
    11. Patients at risk for exposing others to their blood or body fluids and hence requiring Postexposure Prophylaxis
    12. Liver Function Test Abnormality (specifically ALT and AST transaminase increases) of unknown reason
    13. Chou (2014) Ann Intern Med 161(1): 31-45 [PubMed]
  • Lab
  • Screening Protocol
  1. Step 1: Hepatitis B Surface Antigen (HBsAg)
    1. Positive: Go to Step 2
    2. Negative: May still represent Hepatitis B inactive carrier state
  2. Step 2: Differentiate Chronic Infection vs Immunity
    1. Hepatitis B Core Antibody
    2. Hepatitis B Surface Antibody (immune)
  1. Hepatitis B Surface Antigen: HBsAg
    1. Protein found on the surface of the Hepatitis BVirus
    2. First detectable agent in Acute Hepatitis B Infection
    3. Present as early as Incubation Period
    4. Found in high serum levels in both acute and Chronic Hepatitis B, and indicates the patient is infectious
  2. Hepatitis B Envelope Antigen: HBeAg
    1. Highly Infectious State
    2. Chronic Infection
  • Labs
  • Detectable Antibodies
  1. Hepatitis B Surface Antibody: xHBsAb IgG
    1. Prior Hepatitis B Infection with recovery and Immunity OR
    2. Prior Hepatitis B Vaccine with Immunity
  2. Hepatitis B Core Antibody: xHBcAb IgM and IgG
    1. Present at the time of Acute Hepatitis B symptoms
      1. Core IgM Antibody suggests recent Hepatitis B Infection within the last 6 months
      2. Core IgG Antibody persists lifelong (regardless of recovery)
    2. Covers Convalescent period
      1. Window between HBsAg clearance to xHBsAb conversion
      2. HBsAg negative during this time
  3. Hepatitis B Envelope Antibody: xHBeAb IgM and IgG
    1. Low Infectivity
    2. Predicts Hepatitis B Resolution
  1. Susceptible
    1. HBsAg negative
    2. xHBcAb negative
    3. xHBsAb negative
  2. Immune from natural Hepatitis B Infection
    1. HBsAg negative
    2. xHBcAb positive
    3. xHBsAb positive
  3. Immune from Hepatitis B Vaccine
    1. HBsAg negative
    2. xHBcAb negative
    3. xHBsAb positive
  4. Acute Hepatitis B Infection
    1. HBsAg positive
    2. xHBcAb IgM positive
    3. xHBcAb IgG positive
    4. xHBsAb negative
  5. Chronic Hepatitis B Infection
    1. HBsAg positive
    2. xHBcAb IgM negative
    3. xHBcAb IgG positive
    4. xHBsAb negative
  6. Indeterminate (resolved or resolving infection, False Positive xHBcAb, Chronic Hepatitis B)
    1. HBsAg negative
    2. xHBcAb positive
    3. xHBsAb negative
  7. References
    1. CDC Hepatitis B Serologic Chart
      1. https://www.cdc.gov/hepatitis/hbv/pdfs/serologicChartV8.pdf
  1. Stage 1: Immune Tolerant or Incubation Period
    1. Characteristics
      1. DNA Replication very active in this stage
      2. Prolonged stage in newborns
      3. Asymptomatic (Serum Aminotransferases normal)
    2. Incubation (4-12 weeks)
    3. Late incubation (1-2 weeks)
      1. HBsAg Positive
  2. Stage 2: Immune Response
    1. Characteristics
      1. Immune response causes hepatic cell destruction
        1. Serum Aminotransferases increased
      2. High risk stage for Chronic Hepatitis B progression
      3. Symptom flares may occur if Immunocompromised
      4. Conversion to Stage 3
        1. Occurs in most adults rapidly
        2. Others convert 5-15% per year
    2. Early Acute
      1. HBsAg Positive
      2. HBeAg Positive
    3. Acute (2-12 weeks)
      1. HBsAg Positive
      2. HBeAg Positive
      3. xHBc IgM Antibody Positive
      4. xHBc IgG Antibody Positive
    4. Acute and Seroconversion (transitions into Stage 3)
      1. HBsAg Positive
      2. xHBc IgM Antibody Positive
      3. xHBc IgG Antibody Positive
      4. xHBe IgG Antibody Positive
  3. Stage 3: Inactive carrier state (3-6 months)
    1. Characteristics
      1. Viral replication stops and transaminases normalize
      2. Possibly infectious and convalescent stage
      3. Conversion to Stage 4: 3% per year
    2. HBsAg Negative (but positive in chronic active infection)
    3. xHBc IgM Antibody Positive
    4. xHBc IgG Antibody Positive
    5. xHBe IgG Antibody Positive
  4. Stage 4: Immune and Early Recovery
    1. xHBc IgG Antibody Positive
    2. xHBe IgG Antibody Positive
    3. xHBs IgG Antibody Positive