Hepatitis D laboratory findings
Hepatitis D laboratory findings On the Web
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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.
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. 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. Even in cases of HBsAg seroconversion, or liver transplant, anti-HDV antibodies may be detected during several years.
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.
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.
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.
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.
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.
Below is a diagram representing the assessment of patients with hepatitis D:
|Anti-HDV IgG antibody||
|Anti-HDV IgM antibody||
- Liver biopsy is not indicated for the routine diagnosis of acute hepatitis D, unless serologic diagnosis is inconclusive. Liver biopsy is indicated when patients are HDV RNA positive, in which case, it will help assess the severity of liver disease.
- Due to the inability of noninvasive markers of fibrosis to predict the correct stage of the disease, liver biopsy should be performed in patients with hepatitis D.
- Findings are similar to those observed in HBV infection. Lymphocytic infiltrates may be observed in hepatocytes.
- Immunohistochemical staining may be positive for HDV antigen with suppression of HBsAg in case of superinfection.
Acute HBV-HDV Coinfection
- 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
- 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
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. Patients coinfected with HDV often show:
Coinfection with HIV
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