LabMed

Hepatitis D (HDV)

At a Glance

Hepatitis D virus (HDV; aka Delta hepatitis or Delta agent) is a small RNA virus that can replicate only in cells also infected with the hepatitis B virus (HBV), which provide the envelope structures for HDV. Hepatitis B replication is usually suppressed in active HDV infections.

Hepatitis D is rare in the United States and Western Europe, except in intravenous drug users, but is more common in the Amazon Basin, Central America, Eastern Europe, the Mediterranean Basin and Central Africa, and regional outbreaks can occur elsewhere.

Acute hepatitis D, acquired at or near the time of HBV infection (coinfection), increases the likelihood of fulminant HBV infection but not of chronic HBV. HDV acquired during the chronic phase of hepatitis B (superinfection) may present as a severe acute hepatitis or as an exacerbation of chronic hepatitis B, often with rapid progression; 60-70% of patients with chronic hepatitis D progress to cirrhosis.

Consider testing for hepatitis D in patients who are HBV-infected as evidenced by HBV surface Ag, or HBV core Igm or total antibody, and who:

  • are intravenous drug users

  • are immigrants from an endemic area

  • have an unusually severe, fulminant, or prolonged course of acute HBV

  • have an episode of acute hepatitis during chronic HBV infection

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Because HDV requires HBV to replicate, test for HDV only in patients who are HBV positive, as shown by HBsAg, HBcAb, or HBcIgM seroreactivity.

HDV serological or PCR tests are available from reference laboratories.

Acute HDV coinfection: To document coinfection, the patient should be HBcIgM positive. HDV IgM becomes positive during the acute phase of HDV infection, although only antigen and HDV RNA may be found early.

Chronic HDV superinfection: HBV core Ab will be positive. Because HDV suppresses HBV replication, HBsAg may be negative, although the patient usually has a history of surface antigen positivity. HDV IgM becomes positive during the acute phase of HDV infection, although only antigen and HDV RNA may be found early.

Chronic HDV: HBV core Ab will be positive. Because HDV suppresses HBV replication, HBsAg may be negative, although the patient usually has a history of surface antigen positivity. HDV total Ab will be positive, and HDV IgM will be negative, whereas HDV Ag and RNA will be positive (Table 1).

Table 1.

Hepatitis D Tests
Test Application and Interpretation
Liver markers; ALT, AST, etc. Elevated in active HDV disease
Hepatitis B markers Evidence of HBV infection is required to diagnose hepatitis D.
HDV IgM Positive in acute HDV infection, either coinfection or superinfection; becomes positive relatively late in acute infection; persists as infection becomes chronic, but declines if infection is cleared, and eventually disappears even in chronic infections
HDV total Ab Negative during acute HDV, becomes positive later; persists as infection becomes chronic, but declines if infection is cleared
HDV Ag Positive early in acute infection, either coinfection or superinfection, but becomes negative after HDV antibodies become detectable
HDV RNA by RT-PCR Positive in both acute and chronic HDV; cleared if infection is controlled by host.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

As with all serological tests, false positives occur, particularly with IgM assays.

What Lab Results Are Absolutely Confirmatory?

HDV tests are complex and done in only a few laboratories. HDV RNA is the test that best correlates with active disease of all stages but, in most cases, has not been validated with an extensive range of genotypes.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

HDV antigen is sometimes performed on liver biopsies to confirm serological diagnosis.

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