Hepatitis Delta Virus - HDV

Hepatitis delta virus (HDV) is a subviral agent that is dependent on the hepatitis B virus (HBV) surface antigen (HBsAg) for its life cycle. HDV infection cannot occur in the absence of HBV, but occurs as an acute coinfection with HBV or as a superinfection. Acute infection will cause an early increase in alanine aminotransferase (ALT).

Quick Answers for Clinicians

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Diagnosis

Indications for Testing

Worsening of liver disease in hepatitis B virus (HBV)-infected individual

Laboratory Testing

  • Diagnosis
    • Hepatitis D virus (HDV) RNA
    • Presence of anti-HDV antibodies
    • Test only HBV-positive patients
  •  Testing
    • HDV total antibodies (IgG and IgM)
      • Qualitative only
      • Can be used in acute or chronic HDV
      • Confirms presence of HDV in individual with chronic HBV infection
    • Polymerase chain reaction (PCR) test
      • Confirms and quantifies presence of HDV  
      • Use for monitoring treatment response and viral clearance
    • Cotesting to determine HBV status
      • Hepatitis B core IgM (IgM anti-HBc)
        • Use to differentiate between acute and chronic disease
      • HBV surface antigen (HBsAg)
        • Present in acute and chronic disease states
      • HBV viremia
        • Quantifies viral load
        • Can be followed over time (Romeo, 2015)
    • Genotyping – generally not commercially available as clinical significance not yet established (Romeo, 2015)

Prognosis

  • HDV more severe than HBV alone
    • HDV increases risk for progression to cirrhosis and for hepatocellular carcinoma
  • Hepatitis D genotypes 2 and 3 seem to have a worse prognosis (Romeo, 2015)
  • Clinical course of hepatitis D genotypes 5-8 still unclear (Romeo, 2015)
  • Hepatitis B genotype may influence severity as well – genotype C seems to have worse outcome (Romeo, 2015)
  • HDV RNA viral load >600,000 IU/mL is associated with progression to cirrhosis (Romeo, 2015)

Differential Diagnosis

Screening

Although screening for hepatitis delta virus (HDV) may be beneficial in patients with hepatitis B virus (HBV), there are currently no U.S. consensus statements (for example, from the CDC or the American Association for the Study of Liver Diseases [AASLD]) that recommend general screening.

Monitoring

Hepatitis D RNA viral load quantification is used to monitor response to therapy and viral clearance.

Background

Epidemiology

  • Prevalence – ~15-20 million people worldwide are hepatitis delta virus (HDV) infected (Noureddin, 2014)
  • Rare in U.S. (CDC)
  • Age – 20s-30s (peak)
  • Transmission – requires mucosal or subcutaneous exposure to bloodborne pathogen, similar to hepatitis B

Organism

  • Negative strand RNA virus
  • Requires hepatitis B virus (HBV) to supply envelope proteins for its assembly into mature virions (HBV surface antigen [HBsAg] presence)
  • 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 bloodborne pathogen (eg, HBV, HIV)
  • Organ transplant recipient
  • Hemodialysis
  • Sexual transmission is not predominant transmission route, except in a few areas (eg, Taiwan)
  • Perinatal transmission – rare

Clinical Presentation

  • Different disease states
    • HBV/HDV coinfection
      • Disease process similar to HBV acute infection – nausea, anorexia, jaundice
      • 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

ARUP Lab Tests

Diagnose hepatitis delta virus (HDV) infection in patient with documented acute or chronic hepatitis B virus (HBV) and risk for HDV infection

Consider ordering HBV core IgM antibody to determine whether HDV infection is a coinfection or a superinfection with HBV

Confirm and quantify presence of HDV

Related Tests

Diagnose hepatitis delta virus (HDV) infection in patient with documented acute or chronic hepatitis B virus (HBV) and at risk for HDV infection

Consider ordering HBV core IgM antibody to determine whether HDV infection is a coinfection or a superinfection

Determine whether HDV infection is acute rather than chronic

Consider ordering HBV core IgM antibody to determine whether HDV infection is a coinfection or a superinfection with HBV

Can be ordered as part of the acute hepatitis panel which includes hepatitis A virus (HAV) IgM, HBV core antibody IgM, HBV surface antigen (HBsAg), and hepatitis C virus (HCV) antibody to determine if patient has acute HBV infection

Refer to hepatitis panel with reflex to HBsAg confirmation

Can be ordered as part of the acute hepatitis panel which includes HAV IgM, HBV core antibody IgM, HBsAg, and HCV antibody

Refer to hepatitis panel with reflex to HBsAg confirmation

Reflex pattern: if results for HBsAg screen are repeatedly reactive with an index value between 1.00 and 50.00, then HBsAg confirmation will be added

Detect acute or chronic HBV infection

Indicate stage of infection

Use to monitor patients with chronic HBV infection and known positive HBsAg

Detect and quantify HBV

If virus is not detected, test result will be reported as <1.3 log IU/mL (<20 IU/mL); if virus is detected but number of copies is not accurately quantified, test result will be reported as not quantified

Detect and quantify HBV

Determine antiviral drug resistance

Reflex pattern: if HBV quantitative NAAT result is ≥3.0 log IU/mL (1,000 IU/mL), then HBV genotype by sequencing will be added

Initial screening for hepatobiliary inflammation

Panel includes albumin; alkaline phosphatase (ALP); aspartate aminotransferase (AST); alanine aminotransferase (ALT); bilirubin, direct; protein, total; and bilirubin, total

Medical Experts

Contributor

Slev

Patricia R. Slev, PhD

Associate Professor of Clinical Pathology, University of Utah

Section Chief, Immunology

Medical Director, Serologic Hepatitis and Retrovirus and Immunology Core Laboratory

Co-Medical Director, Microbial Immunology, at ARUP Laboratories

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®