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 co-infections, 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

Prognosis

• 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

• Viral
  • Cytomegalovirus
  • Epstein-Barr virus
  • Herpes simplex virus
  • Varicella-zoster virus
  • Hepatitis A, B, C or E 
• Toxin exposure
  • Alcohol
  • Tetrachloride
• Nonalcoholic acute steatohepatitis
• Drug-induced hepatitis
  • Acetaminophen
  • Antiseizure medications
  • Isoniazid (Nydrazid)
  • Oral contraceptives
  • Rifampin (Rifadin)
  • Sulfonamides
• Autoimmune disease
  • Systemic lupus erythematosus
  • Primary biliary cirrhosis
  • Sclerosing cholangitis
  • Autoimmune hepatitis
• Bacterial infection
  • Leptospira spp
  • Coxiella burnetii (Q-fever)
  • Rickettsia rickettsii (Rocky Mountain spotted fever)
  • Treponema pallidum (secondary syphilis)
  • Sepsis
  • Rickettsia typhi (typhus fever) 
• Granulomatous
  • M. tuberculosis
  • Sarcoidosis
• Hereditary
  • Wilson disease
  • Hemochromatosis
  • Alpha-1-antitrypsin deficiency
• Ischemia
• Parasitic
  • Liver trematodes
  • Toxocara spp

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

• 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

Treatment

• Acute HDV infection – supportive care
• Chronic HDV infection – interferon-alfa (standard or pegylated), liver transplant (in chronic end-stage, fulminant, acute disease)

Tests generally appear in the order most useful for common clinical situations

General

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• Rizzetto M. Hepatitis D: clinical features and therapy. Dig Dis. 2010; 28 (1) :139-143.PubMed
• Rizzetto M. Hepatitis D: the comeback?. Liver Int. 2009; 29 Suppl 1 :140-142.PubMed
• Taylor JM. Hepatitis delta virus. Virology. 2006; 344 (1) :71-76.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
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• Yurdaydin C, Idilman R, Bozkaya H, Bozdayi AM. Natural history and treatment of chronic delta hepatitis. J Viral Hepat. 2010; 17 (11) :749-756.PubMed

Cirrhosis
Hepatitis, Acute
Hepatitis, Autoimmune
Hepatocellular Carcinoma
Liver Disease Evaluation