Hepatitis Delta Virus - HDV

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

Indications for Testing

  • Abrupt onset of nausea, anorexia, or jaundice; patient with known chronic HBV with worsening liver disease

Laboratory Testing

  • HDV antibody tests – positive in acute disease; should be followed by HDV antigen (HDsAg) testing, IgM antibody by EIA or ELISA and by HBsAg to confirm persisting chronic HBV
  • In acute coinfections, HDsAg appears early, after HBV 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-HBV HBsAg core antibody IgM and HDsAg helps differentiate coinfections (present) from superinfections (absent)
  • PCR identifies HDV RNA – quantification tests are not yet standardized; viral load results do not necessarily correlate with disease
    • Perform if antibodies negative and high suspicion for reconverted HDV disease


  • Based on the following
    • 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) Testing Algorithm

Hepatitis Virus Screening Algorithm

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.


  • Prevalence – an estimated 70,000 people in the U.S. are HDV-infected
  • 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) distributed by geography except for genotype 1, which 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
  • Not predominantly sexually transmitted except in a few areas (eg, Taiwan)
  • Perinatal – rare

Clinical Presentation

  • Two different disease courses – coinfection, superinfection
  • HBV/HDV coinfection
    • Disease process similar to HBV acute infection – nausea, anorexia, jaundice
    • Biphasic type of hepatitis
    • 70-80% of chronic HBV patients who are coinfected with HDV develop fulminant liver failure
    • May evolve to chronic HDV disease
  • 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

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

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

Additional Tests Available

Hepatitis B Virus Core Antibody, IgM 0020092
Method: Qualitative Chemiluminescent Immunoassay


Confirm HBV prior to HDV testing

Hepatitis B Virus Surface Antigen with Reflex to Confirmation 0020089
Method: Qualitative Chemiluminescent Immunoassay 


Document chronic HBV infection

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 G. Clinical features of hepatitis D. Semin Liver Dis. 2012; 32(3): 228-36. PubMed

Hughes S, Wedemeyer H, Harrison P. Hepatitis delta virus. Lancet. 2011; 378(9785): 73-85. 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 M. 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: December 2015