Boosting the sensitivity of the assay for capsid-antibody-complex and its clinical evaluation

Chronic infection of Hepatitis B virus (HBV) continues to plague 3% of the world population with heavier burden in certain ethnic groups such as Aboriginal and Torres Strait Islander people in Australia. Monitoring the liver function is of central importance in the management of chronic hepatitis B (CHB). However, the commonly used biomarker such as serum alanine aminotransferase (ALT) is of limited sensitivity. Our previous study proved the existence of capsid-antibody-complexes (CACs) in sera of CHB patients and suggested its role in HBV-induced hepatitis. Supported by the last round of ACH2 funding, we developed and validated a novel ELISA assay for quantification of CACs. The level of serum CACs was found to reflect intrahepatic inflammation and outperformed ALT as noninvasive marker for liver injury. Here, we plan to further enhance the sensitivity of this assay by complementing it with the Single Molecular Counting (SMC) technology. This will deliver improved analytical accuracy in samples with low level of CACs. Furthermore, we will explore the clinical value of this assay by monitoring its dynamics after initiation of antiviral therapy and compare it with current serological and biochemical biomarkers. This improved assay can provide a new precision biomarker for liver function normalization. It may also bring implications on safer withdrawal of nucleoside analog and improved rate of functional cure.