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]


The diagnosis of hepatitis D is made by the detection of HDV RNA in circulation, with RT-PCR. The levels of HBsAg may be used during treatment to evaluate the response, and determine the duration of therapy. After recovery, markers of HDV infection, such as IgM and IgG antibodies disappear within months. Liver biopsy is indicated in HDV RNA positive patients, to assess the stage of liver disease. Findings in liver biopsy are similar to those observed in HBV infection. Coinfection with HIV and HCV should be ruled out in HDV infected patients. Serologic markers such as HDV RNA, HDAg, and IgM and IgG anti-HD antibodies may persist for longer periods in chronic hepatitis D.

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.[1] Positive HDV antibodies do not necessarily represent active infection, since HDV RNA might have been cleared away (recovery), while the antibodies may remain in circulation for longer periods of time.[2][3] Even in cases of HBsAg seroconversion, or liver transplant, anti-HDV antibodies may be detected during several years.[3][4]

During therapy, the decrease in the levels of HBsAg may be used to determine the duration of treatment. It is also important to determine the levels of HBV DNA, in order to assess the need for an HBV polymerase inhibitor.[5]

The active form of the HDV infection was initially diagnosed by the detection of anti-HDV IgM antibodies. However, today acute active infection is confirmed with real-time PCR, by detecting serum HDV RNA.[6]

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.[7][8] 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.[9]

According to different studies, it hasn't been noted an association between HDV RNA levels, HBsAg titre, liver test results and the stage of liver disease. Therefore, liver biopsy remains an important tool to assess pathological changes in liver histology.[1]

Each of the markers of HDV infection, including IgM and IgG antibodies, disappears within months after recovery. In chronic hepatitis D, HDV RNA, HDAg, and IgM and IgG anti-HD antibodies persist for longer periods.[10]

Below is a diagram representing the assessment of patients with hepatitis D:

Hepatitis D diagnosis Adapted from Treatment Options for Hepatitis Delta Virus Infection - Springer Science[5]

Diagnostic Markers

The table below describes the significance of diagnostic markers in HDV infection. [1]

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


  • Marker of HDV replication
  • Positive in chronic infection
  • Negative in spontaneous or treatment-induced viral clearance


  • Useful in monitoring or predicting treatment response


  • Must be positive for HDV infectivity


  • Positively correlated with HDV RNA
  • Falling titer signals HBsAg loss, and hence HDV clearance
  • Useful in monitoring or predicting treatment response
  • Negative in an estimated 85% of patients
  • Associated with detectable anti-HBe


  • 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
  • Increased in most patients
  • Does not correlate well with degree of histological liver damage

Liver Biopsy:

Acute HBV-HDV Coinfection

Acute coinfection of HDV with HBV is characterized by:[11]

  • Appearence of HBsAg, HBeAg and HBV DNA in serum during incubation
  • Appearence of anti-HBc at onset of clinical disease
  • Appearence of IgM anti-HD, HDV RNA, HDAg in serum
  • Anti-HDV antibodies develop late in acute phase and usually decline after infection to subdetectable levels
  • If HDAg is detectable early during infection, it disappears as anti-HDV appears
  • All markers of viral replication disappear in early convalescence, and both IgM and IgG anti-HD disappear within months to years after recovery

HBV-HDV Superinfection

Superinfection of HDV with HBV is characterized by:[11]

  • Persistent HDV infection
  • HDV viremia appears in serum during preacute phase
  • High titres of IgM and IgG anti-HDV are detectable in acute phase, persisting indefinitely
  • Titre of HBsAg declines when HDAg appears in serum
  • Progression to chronicity is associated with persisting high levels of IgM anti-HD and IgG anti-HD
  • HDAg and HDV RNA remain detectable in serum and liver
  • Viremia is associated with active liver disease

Viral Dominance

The simultaneous presence of HBV, HDV and sometimes HCV, influences the serologic findings in each patient. Infection by HDV and HBV (either in coinfection or superinfection) suppresses the replication of HBV genome.[1] Patients coinfected with HDV often show:[13][14][15]

Once infection with HDV is cleared, either by host's immune system or with interferon treatment, replication of HBV will then be reactivated.[16]

In prolonged infections, both viruses may become dominant. In which case, serologic levels of HBV DNA and HDV RNA may fluctuate.[17][18]

In patients infected with HCV, along with HDV and HBV, the HDV is the dominant virus. It is able not only to suppress the replication of HBV, but also to inhibit the replication of HCV.[1]

Coinfection with HIV

Patients infected with the HDV should be screened for concomitant infection with HIV.[13][15]


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