Diagnosis
Every HBsAg positive patient (patient with HBV infection) should be tested for the hepatitis delta virus. The first step is often a test for anti-HDV antibody (a protein produced following an immune response to the virus) followed by a test for HDV RNA.
In cases of HBV-HDV coinfection, HBsAg, HBeAg (both proteins made by HBV) and HBV DNA all appear in serum (a component of blood) during the incubation period. IgM antibodies (a class of antibodies) against HBV core antigen (Anti-HBc protein) appear at the onset of clinical disease and are indicative of acute coinfection. The HDV markers, anti-HDV IgM (IgM antibodies) and the HDAg appear in the serum subsequently.
In the acute (early) phase of the HDV superinfection, there are high titers (amounts) of IgM and IgG (another common class of antibody) anti-HDV antibodies and the only antibody against the HBc is anti-HBc IgG.
Chronicity is defined by the persistently increasing (1) titers of anti-HDV antibodies and (2) HDV RNA levels. However quantifying the levels of HDV RNA has been difficult as the relevant assays are not standardized and the results are often not comparable due to different sensitivities of the assays used. Recently, however, consensus commercial kits have also become available, overcoming many of the standardization issues.
If HDV RNA is positive, the next steps are to perform liver biopsy and fibroscan to understand the extent of the disease. This is referred to as the grading and staging of liver disease. Surveillance for hepatocellular carcinoma (liver cancer) is carried out by ultrasound and antiviral therapy may be explored. HDV RNA quantification is indicated when antiviral treatment is planned.
The assessment of the severity of the liver disease involves an assessment of biochemical markers of liver function, including AST, ALT, GGT, alkaline phosphatase, bilirubin, serum albumin and globulins, INR, creatinine and complete blood counts. Other causes of chronic liver disease are systematically excluded before the final diagnosis is made.
HDV genotyping, performed by some research laboratories, may help to identify patients with a higher or lower risk of developing end-stage liver disease, and response to treatment.
Author: Minaam Abbas