Hepatitis Delta Virus - HDV

Diagnostic Algorithm

  Hepatitis Delta Virus (HDV) Testing Algorithm

  Hepatitis Virus Screening Algorithm

Clinical Background

Hepatitis delta virus (HDV) is a subviral agent that is dependent on the hepatitis B (HBV) virus for its life cycle; therefore, HDV infection cannot occur in the absence of HBV infection.

Epidemiology

• Prevalence – an estimated 70,000 people in the U.S. are HDV-infected
• Age – 20s-30s (peak)
• Transmission – parenteral

Organism

• HDV is an RNA virus

Risk Factors

• Transfusion with blood or blood products prior to 1990
  • Current transfusion risk is 1/400,000 units transfused
• Previous/concurrent infection with blood-borne pathogen (eg, HBV, HIV)
• History of intravenous drug or intranasal cocaine use
• Organ transplant recipient
• Hemodialysis

Clinical Presentation

• Three different disease courses – coinfection, superinfection, and chronic
• HBV/HDV coinfection
  • Disease process similar to HBV acute infection – nausea, anorexia, jaundice
  • 70-80% of chronic HBV patients who are co-infected with HDV develop fulminant liver failure
• HDV superinfection superimposed on chronic HBV
  • Worsening liver disease
  • More common course associated with fulminant liver failure
• HDV chronic – associated with cirrhosis and liver failure

Treatment

• Acute HDV infection – supportive care
• Chronic HDV infection – interferon-alfa, liver transplant

Diagnosis

• Indications for testing – abrupt onset of nausea, anorexia or jaundice; patient with known chronic hepatitis B with worsening liver disease
• Laboratory testing
  • HDV antibody tests– positive in acute disease; should be followed by hepatitis B virus antigen (HBsAg) testing and IgM antibody by EIA
  • In acute co-infections, hepatitis D antigen (HDVAg) appears early, after hepatitis B virus surface antigen, and disappears with convalescence
    • Acute HDV infections are associated with anti-HDV IgM antibody
    • Usually, only chronic cases demonstrate IgG antibody
    • Both antibodies usually disappear following convalescence
    • Simultaneous assessment of anti-hepatitis B virus core antibody IgM and HDVAg help differentiate coinfections (present) from super-infections (absent)

Differential Diagnosis

• Viral
  • Cytomegalovirus (CMV)
  • Epstein-Barr virus (EBV)
  • Herpes simplex virus (HSV)
  • Varicella-zoster virus (VZV)
  • Hepatitis A, B, C or E 
• Toxin exposure
  • Alcohol
  • Tetrachloride
• Nonalcoholic acute steatohepatitis (NASH)
• Drug-induced hepatitis
  • Acetaminophen
  • Antiseizure medications
  • Isoniazid (Nydrazid)
  • Oral contraceptives
  • Rifampin (Rifadin)
  • Sulfonamides
• Autoimmune disease
  • Systemic lupus erythematosus (SLE)
  • Primary biliary cirrhosis (PBC)
  • Sclerosing cholangitis
  • Autoimmune hepatitis (AIH)
• Bacterial infection
  • Leptospirosis
  • Q-fever (Coxiella burnetii)
  • Rocky Mountain spotted fever (Rickettsia rickettsii)
  • Secondary syphilis (Treponema pallidum)
  • Sepsis
  • Typhoid fever (Rickettsia typhus) 
• Granulomatous
  • Mycobacterium tuberculosis (TB)
  • Sarcoidosis
• Hereditary
  • Wilson disease
  • Hemochromatosis
  • Alpha-1-antitrypsin deficiency (AAT)
• Ischemic
• Parasitic
  • Liver trematodes
  • Toxocariasis

Pharmacogenetics and Therapeutic Drug Monitoring

Screening

Monitoring

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Hepatitis B Virus Core Antibody, IgM 0020092 Method: Chemiluminescent Immunoassay	Additional testing should be performed prior to HDV testing to document hepatitis B infection
Hepatitis B Virus Surface Antigen with Reflex to Confirmation 0020089 Method: Chemiluminescent Immunoassay	Useful to document chronic hepatitis B infection

General References