Poster Presentation Lorne Infection and Immunity 2022

High prevalence of Capsid-antibody-complexes (CACs) in sera of chronic hepatitis B patients and its association with chronic liver disease (#230)

Xiaonan Zhang 1 , Yijie Tang 2 , Mingzhu Xu 2 , Wei Lu 2 , Min Wu 2 , Cong Wang 2 , Reena Ghildyal 1 , Zhanqing Zhang 2
  1. University of Canberra, Bruce, ACT, Australia
  2. Shanghai Public Health Clinical Center, Fudan University, Shanghai, China

Hepatitis B Virus (HBV) infects a quarter of a billion people worldwide and is responsible for a series of liver diseases from hepatitis, cirrhosis to hepatocellular carcinoma.  The current dogma holds that there are two major viral/subviral particles, i.e., virions (Dane particle) and surface antigen particles (spherical and filamentous) which is currently under challenge by observations of a variety of incomplete viral particles. We recently proposed the existence of Capsid-Antibody-Complexes (CACs) which results from the release of naked capsids from hepatocytes and binding of specific antibodies in circulation.  CACs contains immature viral DNA and a significant amount of HBV RNA (PMID: 30282709). In this study, we further investigate the prevalence of such particles in chronic carriers or hepatitis patients.  We first developed a microplate-based semi-quantitative assay using C1q to capture immune complexes and capsid-horseradish peroxidase to detect anti-core antibody within them.  The specificity of this method was confirmed by a series of samples of non-HBV aetiologies (Hepatitis C, Nonviral hepatitis, Systemic Lupus Erythematosus etc). In HBV infected individuals, a high prevalence of CACs (77%, n=220) was observed indicating the near-universal existence of this particle type. Quantitative PCR measurement of HBV DNA and RNA in C1q-captured immune complexes showed significant enrichment of viral nucleic acids which coincides with the molecular composition of CACs. Intriguingly, the level of CACs strongly correlates with ALT in both HBeAg positive and negative patients. (ALT e+  r=0.62, P<0.0001, e- r=0.66, P<0.0001) suggesting its role in immunopathology of chronic hepatitis B. Indeed, preliminary data showed significant higher CACs level in patients with histological evidence of hepatic inflammation and complement-deposition.  In conclusion, the high prevalence of Capsid-antibody-complexes in chronic hepatitis and their association with liver necroinflammation suggests the underestimated roles of virus-specific immune complexes in HBV-induced liver pathology.