Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (186 page)

BOOK: Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis
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HDV
   HDV, delta agent, is a small defective single-stranded RNA virus enveloped by hepatitis B surface antigens. HDV requires simultaneous HBV infection but relies on HBV only for envelope protein (HBs). The epidemiology of HDV infection is similar to HBV except that sexual and perinatal infection is less efficient. Although uncommon in the United States, HDV is distributed worldwide, with perhaps 5% of HBV-infected patients coinfected with HDV.
   HDV infection may be transmitted simultaneously with HBV infection. In these patients, clinical manifestations may be similar to patients with HBV infection alone, but coinfection is often more severe in terms of clinical signs and symptoms. In HBV/HDV coinfection, the risk for progression to chronic hepatitis is no greater than is seen in HBV infection alone.
   HDV may also be transmitted to patients with preexisting chronic HBV infection. Such HDV superinfections usually lead to clinical deterioration, increased chronicity, and may lead to ALF.
   HDV infection may be suspected on the basis of exposure in regions of high endemicity, history of injection drug abuse, unusually severe HBV disease, or deterioration in chronic HBV infections.
   Antigen detection is the most reliable laboratory test for diagnosis, but levels may be variable. Serum HDVAg and HDV-RNA appear during the incubation period after the appearance of HBsAg and before a rise in ALT, which often shows a biphasic elevation. HBsAg and HDVAg are transient; HDVAg resolves with clearance of HBsAg. Total anti-HDV supports a diagnosis; anti-HDV-IgM is not reliable for distinguishing between acute and chronic infection but is detectable more often than anti-HDV-IgG. In HBV/HDV coinfections, detectable anti-HDV elevations are not clearly predictable, may be of low titer, and often disappear with resolution of acute infection. In superinfection, however, high anti-HDV levels are seen, and these last indefinitely. Determination of the class of anti-HBc, IgG versus IgM, can help distinguish between HDV coinfection and superinfection. Chronic HDV infection is more severe and has higher mortality than other types of viral hepatitis. The risk of HCC is threefold greater in patients with chronic HBV infection in whom anti-HDV is detected compared to patients who are negative.
   
HDV diagnosis
(see Tables 5-11 and 5-12)

Commercial assays for detection of HDV antigen, antibody, and RNA are commercially available but not FDA approved in the United States.

   Anti-HDV positive: HDV infection
   Anti-HDV positive, HBsAg positive, anti-HBc-IgM positive: HBV/ HDV coinfection. HDAg, anti-HDV-IgM, and HDV RNA may be detected. Low titer anti-HDV-total appears late.
   Anti-HDV-total positive, anti-HBc-IgM negative, HBsAg positive, anti-HBc-IgG positive, HDV RNA positive, total, and IgM anti-HDV rapidly increase: Acute HDV superinfection. HDAg may be missed. HDAg can be demonstrated on liver biopsy by immunohistochemical staining. HDAg is not detected in chronic HDV infection.
   
HCV

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