Hepatitis D laboratory findings
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Hepatitis D |
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Diagnosis |
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Treatment |
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Hepatitis D laboratory findings On the Web |
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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]
Overview
Hepatitis D should be considered in any individual who is HBsAg positive or that has evidence of recent HBV infection. The diagnosis of hepatitis D is made with the detection of HDV RNA in circulation, by RT-PCR. The levels of HBsAg may be used during treatment to evaluate the response, and determine the duration of treatment. After recovery, markers of HDV infection, such as IgM and IgG antibodies disappear within months. Liver biopsy is indicated in chronic liver disease to evaluate for cirrhosis or fibrosis. Coinfection with HIV and HCV should be ruled out in HDV infected patients.
Laboratory Findings
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:
Diagnostic Markers
The table below describes the significance of diagnostic markers in HDV infection. [1]
| Diagnostic Markers | Significance |
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| Anti-HDV IgG antibody |
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| Anti-HDV IgM antibody |
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| HDV RNA |
Qualitative
Quantitative
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| HBsAg |
Qualitative
Quantitative
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| HBeAg |
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| HBV DNA |
Quantitative
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| ALT |
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Liver Biopsy:
- Liver biopsy is not routinely indicated in diagnosis of acute hepatitis D unless the serologic diagnosis of hepatitis is inconclusive. However, liver biopsy is indicated in chronic liver disease to evaluate for cirrhosis or fibrosis.
- Histopathologic findings are similar to that observed in HBV infection. Acidophilic cytoplasm in hepatocytes with lymphocytic infiltrates may be observed.
- Immunohistochemical staining may be positive for HDV antigen with suppression of HBsAg in case of superinfection.
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
Coinfection with HIV and HCV
Patients infected with the HDV should be screened for concomitant infection with HIV and HCV.[12][13]
Genotyping
The use of genotyping as a diagnostic test is gaining acceptance among different countries. The association of HDV genotype 1 with a higher degree of liver disease, and with a worst response to treatment with pegylated IFN justify the importance of this test.[14]
HDV genotyping is not indicated in North America and Europe as a diagnostic tool, not only because genotype 1 is the most common type in these regions, but also because the different genotypes have responded well to common antiviral treatments.[5]
References
- ↑ 1.0 1.1 1.2 Hughes SA, Wedemeyer H, Harrison PM (2011). "Hepatitis delta virus". Lancet. 378 (9785): 73–85. doi:10.1016/S0140-6736(10)61931-9. PMID 21511329.
- ↑ Wedemeyer H, Manns MP (2010). "Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead". Nat Rev Gastroenterol Hepatol. 7 (1): 31–40. doi:10.1038/nrgastro.2009.205. PMID 20051970.
- ↑ 3.0 3.1 Paraná R, Kay A, Molinet F, Viana S, Silva LK, Salcedo JM; et al. (2006). "HDV genotypes in the Western Brazilian Amazon region: A preliminary report". Am J Trop Med Hyg. 75 (3): 475–9. PMID 16968924.
- ↑ Mederacke I, Filmann N, Yurdaydin C, Bremer B, Puls F, Zacher BJ; et al. (2012). "Rapid early HDV RNA decline in the peripheral blood but prolonged intrahepatic hepatitis delta antigen persistence after liver transplantation". J Hepatol. 56 (1): 115–22. doi:10.1016/j.jhep.2011.06.016. PMID 21762665.
- ↑ 5.0 5.1 5.2 Heidrich B, Manns MP, Wedemeyer H (2013). "Treatment options for hepatitis delta virus infection". Curr Infect Dis Rep. 15 (1): 31–8. doi:10.1007/s11908-012-0307-z. PMID 23242761.
- ↑ Mederacke I, Bremer B, Heidrich B, Kirschner J, Deterding K, Bock T; et al. (2010). "Establishment of a novel quantitative hepatitis D virus (HDV) RNA assay using the Cobas TaqMan platform to study HDV RNA kinetics". J Clin Microbiol. 48 (6): 2022–9. doi:10.1128/JCM.00084-10. PMC 2884474. PMID 20351206.
- ↑ Manesis EK, Schina M, Le Gal F, Agelopoulou O, Papaioannou C, Kalligeros C; et al. (2007). "Quantitative analysis of hepatitis D virus RNA and hepatitis B surface antigen serum levels in chronic delta hepatitis improves treatment monitoring". Antivir Ther. 12 (3): 381–8. PMID 17591028.
- ↑ Le Gal F, Gordien E, Affolabi D, Hanslik T, Alloui C, Dény P; et al. (2005). "Quantification of hepatitis delta virus RNA in serum by consensus real-time PCR indicates different patterns of virological response to interferon therapy in chronically infected patients". J Clin Microbiol. 43 (5): 2363–9. doi:10.1128/JCM.43.5.2363-2369.2005. PMC 1153793. PMID 15872267.
- ↑ Zachou K, Yurdaydin C, Drebber U, Dalekos GN, Erhardt A, Cakaloglu Y; et al. (2010). "Quantitative HBsAg and HDV-RNA levels in chronic delta hepatitis". Liver Int. 30 (3): 430–7. doi:10.1111/j.1478-3231.2009.02140.x. PMID 19840253.
- ↑ Webster, Robert (1996). Encyclopedia of virology plus. San Diego: Academic. ISBN 0120001039.
- ↑ 11.0 11.1 "Hepatitis D" (PDF).
- ↑ Cross TJ, Rizzi P, Horner M, Jolly A, Hussain MJ, Smith HM; et al. (2008). "The increasing prevalence of hepatitis delta virus (HDV) infection in South London". J Med Virol. 80 (2): 277–82. doi:10.1002/jmv.21078. PMID 18098143.
- ↑ Heidrich B, Deterding K, Tillmann HL, Raupach R, Manns MP, Wedemeyer H (2009). "Virological and clinical characteristics of delta hepatitis in Central Europe". J Viral Hepat. 16 (12): 883–94. doi:10.1111/j.1365-2893.2009.01144.x. PMID 19566789.
- ↑ Su CW, Huang YH, Huo TI, Shih HH, Sheen IJ, Chen SW; et al. (2006). "Genotypes and viremia of hepatitis B and D viruses are associated with outcomes of chronic hepatitis D patients". Gastroenterology. 130 (6): 1625–35. doi:10.1053/j.gastro.2006.01.035. PMID 16697726.