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Preventing & screening for hepatitis D

?How to prevent an HDV infection and what is the diagnosis pathway?

Prevention is the same as for HBV 

There is as yet no vaccine against HDV (3). However, since the virus is entirely dependent on HBV, HDV infection can be prevented by immunising against hepatitis B. In France, this vaccine was made mandatory for all children on 1 January 2018 (4). However, immunisation against hepatitis B confers no protection against HDV in people who are already infected with HBV. Rigorous safety precautions when administering blood transfusions and injections cut down HDV transmission via the blood and, since the virus can be sexually transmitted, using a condom blocks this route of entry.

Over the last two decades, improved socioeconomic conditions and higher standards of living together with the introduction of mass hepatitis B immunization programmes have significantly reduced the incidence of HDV infection, especially in southern Europe and around the Mediterranean rim.(3)(5)

Diagnosis pathway

Diagnosing infection with hepatitis D virus (HDV) depends on two blood tests: the first measures the levels of antibody (immunoglobulin or Ig) directed against HDV in the blood and, if the result of this first test is positive, a follow-up test will be performed to detect HDV genetic material, i.e. its ribonucleic acid (RNA) (1). Diagnosis should be undertaken in anyone infected with the hepatitis B virus (HBV) as simultaneous or sequential infection with both viruses can lead to serious or even life-threatening liver diseases. 

Assaying antibody against HDV in the blood 

In immunocompetent individuals, acute HDV infection induces an immune response with the production of IgM and IgG antibodies. IgM can be detected two to three weeks after the onset of symptoms of acute hepatitis and for two to nine months thereafter. Therefore, a test to detect IgM can be useful when it comes to identify patients suffering from acute hepatitis D. It should be noted that specific IgM antibody levels may rise in a patient with chronic hepatitis experiencing a flare-up. In contrast, specific IgG antibodies and total anti-HDV antibody levels persist in the blood even after an acute hepatitis D infection has been overcome as well as in patients with chronic hepatitis D (2). Currently, kits for reliable tests are commercially available (1). Tests to detect total Ig and, to a lesser extent, IgM, are routinely used to screen for HDV infection (2).

Molecular biology and diagnosis

If the level of anti-HDV total antibodies is undetectable, HDV infection is ruled out. However, if the result of the serological test is positive, the serum should be tested for HDV RNA to confirm the diagnosis and quantify the viral load (the number of copies of the virus in a given volume of blood). A molecular biology technique, the real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR), is the most sensitive for this research (2). This phase of the diagnostic process poses the greatest challenge due to the major genetic variability of HDV, which means that few commercially available kits yield accurate quantitative results with all the various different strains of the virus. Nevertheless, the World Health Organization distributes standard reference material to make it possible to harmonise these tests (1-2).

It is worth noting that HDV antigens can be detected in the liver but this invasive technique is not routinely used to diagnose HDV infection (2).

HBV-HDV Typical serologic course

Sources

  1. Brichler S et al. Serological and molecular diagnosis of hepatitis delta virus infection: results of a French national quality control study. J Clin Microbiol 2014; 52: 1694-7
  2. Pathogenesis of and New Therapies for Hepatitis D Koh, Christopher et al. Gastroenterology, Volume 156, Issue 2, 461 - 476.e1
  3. Clinical features of hepatitis D. Farci P1, Niro GA. Semin Liver Dis. 2012 Aug; 32 (3): 228-36
  4. Vaccination calendar 2019. Available online: https://www.rki.de/DE/Content/Kommissions/STIKO/Empfehler/Impfempfänger_node.html
  5. Gaeta GB, Stroffolini T, Chiaramonte M, et al. Chronic hepatitis D: a vanishing disease? An Italian multicenter study. Hepatology 2000; 32 (4 Pt 1): 824-827