Hepatitis D laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jolanta Marszalek, M.D. [2] João André Alves Silva, M.D. [3]

Laboratory Findings

Hepatitis D should be considered in any individual who is HBsAg positive or that has evidence of recent HBV infection. The diagnosis of acute hepatitis D is made after evaluation of serologic tests for the virus. Persons infected with HDV develop anti-HDV antibodies. Accordingly, every individual with an HBsAg positive test result, should be studied for the presence of anti-HDV IgG antibodies.

The active form of the HDV infection was initially diagnosed by the detection of anti-HDV IgM antibodies. However, today the acute infection is confirmed with real-time PCR, by detecting serum HDV RNA.

Patients presenting with liver disease, following HDV infection, should be tested for anti-HDV IgM antibodies, even when the HDV RNA test is negative. This is due to the fact that the hepatitis D virus shows genome variability, which might lead to false-negative results. Although the levels of HDV RNA in the serum do not correlate with the stage of the disease, or liver fibrosis, the HDV RNA quantification may be used to evaluate the response to the antiviral therapy.

The table below describes the significance of diagnostic markers in HDV infection.

Diagnostic Markers	Significance
Anti-HDV IgG antibody	Positive in persons exposed to HDV Persists, even after viral clearance
Anti-HDV IgM antibody	Positive in acute infection Negative in past infection Persists in many patients with chronic infection
HDV RNA	Qualitative Marker of HDV replication Positive in chronic infection Negative in spontaneous or treatment-induced viral clearance Quantitative Useful in monitoring or predicting treatment response
HBsAg	Qualitative Must be positive for HDV infectivity Quantitative Positively correlated with HDV RNA Falling titer signals HBsAg loss, and hence HDV clearance Useful in monitoring or predicting treatment response
HBeAg	Negative in an estimated 85% of patients Associated with detectable anti-HBe
HBV DNA	Quantitative Suppressed by HDV Negative or low levels in most patients May be increased in patients with detectable HBeAg Can reactivate after spontaneous or treatment-induced clearance of HDV
ALT	Increased in most patients Does not correlate well with degree of histological liver damage

Hepatitis D diagnosis Adapted from Treatment Options for Hepatitis Delta Virus Infection - Springer Science