Hepatitis test in the laboratory

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Hepatitis Delta Virus (HDV) is a satellite virus of Hepatitis B virus (HBV) that worsens liver damage in infected individuals. It is recommended to screen for HDV antibodies in patients who test positive for Hepatitis B surface antigen (HBsAg). While the diagnostic accuracy of serological tests for HDV is still uncertain, the findings indicate that tests targeting Anti-HDV IgG demonstrate high accuracy and can function as effective screening tools for HDV.

The results indicated that the sensitivities for the serological tests were 97.4% for Anti-HDV IgG, 51.9% for Total Anti-HDV, and 62% for Anti-HDV IgM. The specificities were 95.3% for Anti-HDV IgG, 80% for Total Anti-HDV, and 85% for Anti-HDV IgM.

“One key finding of this study was that Anti HDV IgG detecting tests performed better than total Anti HDV and IgM-detection tests,” according to investigators. “Our findings may be due to IgM anti-HDV antibody assays failing to detect low antibody titers during specific phases of the infection.”¹

A thorough search was performed across multiple databases, including PubMed, Web of Science, Cochrane Central Register of Controlled Trials, and Scopus, to identify relevant studies. The review included studies that assessed the sensitivity and specificity of serological HDV tests compared to PCR as the reference standard. It covered six studies with 11 study arms, evaluating different testing methods such as ARCHITECT immunoassay, EIA, ELISA, QMAC, RIA, and Western Blot, focusing on Anti-HDV IgG, Total Anti-HDV, and Anti-HDV IgM.

“We expected commercial assays to perform better than In-house in detecting Anti-HDV. However, the reverse was true for our studies,” according to the investiagtors. “It appears In-house methods work better in detecting Anti- HDV. A study evaluating an In-house ELISA test for hepatitis B confirmed this by recording a 100% sensitivity and specificity for the inhouse test.”¹

A limitation of this study is the small number of available publications, indicating a lack of HDV research and testing. This constraint prevented evaluating how factors such as the type and timing of infection, coinfection, superinfection, acute, or chronic might influence test performance and the impact of HDV genotype. The results of this meta-analysis should be interpreted with caution, as most analyzed studies focused on Anti-HDV IgG, while Anti-HDV IgM and Total Anti-HDV were underrepresented. Although a subgroup analysis by immunoglobulin type was conducted, the limited number of studies hindered comparisons.

Reasoning why this study is important because HDV remains widespread and poses significant health risks 40 years after its identification, primarily relying on HBV for its life cycle and infectivity, despite the absence of effective treatments. Chronic hepatitis D is the most severe form of viral hepatitis, requiring the presence of hepatitis B surface antigen (HBsAg), which had a prevalence of about .36% in the US from 2011 to 2016, with 42% of carriers also having HDV antibodies. The low screening rates for HDV, recommending “reflex testing” for patients positive for HBsAg to improve diagnosis rates.²

Management of HDV differs based on whether it occurs as a coinfection or superinfection, with superinfections constituting around 90% of chronic cases and leading to more severe outcomes. Currently, there is no approved therapy for chronic HDV in the US, although pegylated interferon is used off-label, and investigational agents like bulevirtide show promise. Achieving a sustained viral response remains challenging, but combination therapies targeting HBsAg synthesis could offer potential cures for chronic HDV.²

In conclusion, this study highlights the importance of accurate screening for HDV in HBV patients. Although, the limited number of studies and gaps in understanding infection type and HDV genotype necessitate cautious interpretation of the results. Future research should focus on expanding the evidence base and exploring clinical implications to improve patient care.

References

1. Akuffo GA, Ouoba S, Ko K, et al. Assessing the diagnostic accuracy of serological tests for hepatitis delta virus diagnosis: a systematic review and meta-analysis. Sci Rep 14, 18475 (2024). https://doi.org/10.1038/s41598-024-69304-8

2. Bender K. Hepatitis D Characterized as Most Severe, Progressive Viral Hepatitis. Contagion. September 21, 2023. Accessed September 23, 2024. https://www.contagionlive.com/view/hepatitis-d-characterized-as-most-severe-progressive-viral-hepatitis