RNA Profiling Analysis of the Serum Exosomes Derived from Patients with Chronic Hepatitis and Acute-on-chronic Liver Failure Caused By HBV

Abstract

Hepatitis B virus (HBV) is the main causative viral agent for liver diseases in China.In liver injury, exosomes may impede the interaction with chromatin in the target cell and transmit inflammatory, apoptosis, or regeneration signals through RNAs. Therefore, we attempted to determine the potential functions of exosomal RNAs using bioinformatics technology. We performed RNA sequencing analysis in exosomes derived from clinical specimens of healthy control (HC) individuals and patients with chronic hepatitis B (CHB) and acute-on-chronic liver failure caused by HBV (HBV-ACLF). This analysis resulted in the identification of different types and proportions of RNAs in exosomes from the HC individuals and patients. Exosomes from the CHB and HBV-ACLF patients showed distinct upregulation and downregulation patterns of differentially expressed genes compared with those from the HC subjects. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway analysis further confirmed different patterns of biological functions and signalling pathways in CHB and HBV-ACLF. Then we chose two upregulated RNAs both in CHB and HBV-ACLF for further qPCR validation. It confirmed the significantly different expression levels in CHB and HBV-ACLF compared with HC. Our findings indicate selective packaging of the RNA cargo into exosomes under different HBV attacks; these may represent potential targets for the diagnosis and treatment of HBV-caused liver injury.Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease. The World Health Organisation estimates that, globally, 257 million people are living with hepatitis B virus (HBV) infection, which resulted in 887,000 deaths in 2015 1 . Chronic hepatitis B (CHB) includes three phases, i.e. immune-tolerant, immune-active, and inactive phases 2 . In the immune-active phase, various degrees of necroinflammation, with or without fibrosis, are observed in the liver 3 . Hepatitis flares can be controlled with antiviral therapy, but liver failure is a significant cause of overall morbidity, even with antiviral drugs 4 .The median mortality rate associated with acute-on-chronic liver failure (ACLF) has been reported to range from 50% to 90% 5 , which is different from that with hepatitis flares. In China, the plasma exchange-centred artificial liver support system has improved the prognosis of HBV-caused ACLF (HBV-ACLF), but the 1-month mortality rate remains high at 38.4% 4 . A better understanding of the molecular mechanisms of the development and progression of immune-active CHB and HBV-ACLF may allow a more accurate prediction of their outcomes and the optimisation of therapeutic regimens. Therefore, reliable and effective diagnosis and treatment strategies are urgently needed.Exosomes are spheroidal particles with a lipid bilayer membrane, containing various classes of nucleic acids, proteins, and lipids 6 . Exosomes have been recognised as universal intercellular communication vesicles released by cells and able to horizontally transfer biochem...

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