Hepatitis Delta Virus - HDV

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Abrupt onset of nausea, anorexia, or jaundice
  • Known chronic hepatitis B virus (HBV) with worsening liver disease

Laboratory Testing

  • Hepatitis delta virus (HDV) antibody tests
    • Positive in acute disease; should be followed by HDV surface antigen (HDsAg) testing, IgM antibody by enzyme immunoassay (EIA) or enzyme-linked immunoabsorbent assay (ELISA), and by hepatitis B surface antigen (HBsAg) to confirm persisting chronic HBV
    • In acute coinfections, HDsAg appears early, after HBsAg, 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-HBV HBsAg core antibody IgM and HDsAg helps differentiate coinfections (present) from superinfections (absent)
    • Polymerase chain reaction (PCR) test confirms and quantifies presence of HDV


  • Based on
    • Modality of infection – coinfection vs. superinfection
    • HDV genotype – type 3 associated with more severe disease
    • HBV replication by RNA or ELISA – higher numbers associated with more severe disease

Differential Diagnosis

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


  • Prevalence – ~15-20 million people worldwide are HDV infected (Noureddin, 2014)
  • Age – 20s-30s (peak)
  • Transmission – parenteral


  • Natural reservoir is a negative strand RNA virus
  • Requires HBV to supply envelope proteins for its assembly into mature virions
  • Multiple genotypes (1-8) – most are distributed geographically, but genotype 1 is worldwide

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
  • Sexual transmission is not predominant transmission route, except in a few areas (eg, Taiwan)
  • Perinatal transmission – rare

Clinical Presentation

  • 2 different disease courses – coinfection, superinfection
  • HBV/HDV coinfection
    • Disease process similar to HBV acute infection – nausea, anorexia, jaundice
    • Biphasic type of hepatitis
    • May evolve to chronic HDV disease
    • 70-80% of patients with chronic HBV who are coinfected with HDV develop fulminant liver failure
  • HDV superinfection superimposed on chronic HBV
    • Worsening of underlying liver disease (if already present)
    • More common course associated with fulminant liver failure
    • Leads to chronic liver disease in 70-90% of patients
  • Not known if risk of hepatocellular carcinoma is increased in chronic disease
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.

Hepatitis Delta Virus Antibody 0020799
Method: Qualitative Enzyme Immunoassay

Hepatitis Delta Virus (HDV), IgM Antibody, EIA 0098507
Method: Enzyme Immunoassay

Hepatitis Delta Antigen by ELISA 2006450
Method: Qualitative Enzyme-Linked Immunosorbent Assay

Hepatitis Delta Virus by Quantitative PCR 2013881
Method: Quantitative Polymerase Chain Reaction

General References

Chakravarty R. Diagnosis and monitoring of chronic viral hepatitis: serologic and molecular markers. Front Biosci (Schol Ed). 2011; 3: 156-67. PubMed

Farci P, Niro GA. Clinical features of hepatitis D. Semin Liver Dis. 2012; 32(3): 228-36. PubMed

Hughes SA, Wedemeyer H, Harrison PM. Hepatitis delta virus. Lancet. 2011; 378(9785): 73-85. PubMed

Noureddin M, Gish R. Hepatitis delta: epidemiology, diagnosis and management 36 years after discovery. Curr Gastroenterol Rep. 2014; 16(1): 365. PubMed

Olivero A, Smedile A. Hepatitis delta virus diagnosis. Semin Liver Dis. 2012; 32(3): 220-7. PubMed

Pascarella S, Negro F. Hepatitis D virus: an update. Liver Int. 2011; 31(1): 7-21. PubMed

Wedemeyer H, Manns MP. Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead. Nat Rev Gastroenterol Hepatol. 2010; 7(1): 31-40. PubMed

Medical Reviewers

Last Update: October 2017