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Biomarkers for chronic hepatitis b and use thereof

A technology for chronic hepatitis B and liver disease, applied in the field of biomarkers for chronic hepatitis B and its use

Active Publication Date: 2020-04-21
PERFECT CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, published studies on CHB patients rely on quantitative PCR of the 16S rRNA gene, which requires PCR primers specifically designed for each genus or species of interest, thus presenting limitations in terms of throughput and overview of intestinal dysregulation

Method used

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  • Biomarkers for chronic hepatitis b and use thereof
  • Biomarkers for chronic hepatitis b and use thereof
  • Biomarkers for chronic hepatitis b and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0099] Example 1: Overview of intestinal flora

[0100] After paired-end merging, error correction and quality filtering processes, qualified sequences were thinned to 10,000 sequences per sample and clustered into 886 de novo OTUs at the 97% similarity threshold level. Principal component analysis (PCA) plots based on OTU distributions show that the training and test cohorts are fully mixed ( figure 1 ) and the composition of their gut flora were not significantly different (p=0.9, PERMANOVA test). OTU richness and phylogenetic diversity of gut microbiota did not differ significantly between groups. In contrast, the LDA plot based on the OTU distribution showed a clear separation between the CHB group and the control group ( figure 2 , p<0.01, PERMANOVA test). CHB patients exhibit systemic dysbiosis of gut microbiota composition.

Embodiment 2

[0101] Example 2: Disease-specific intestinal flora dysbiosis at the OTU level

[0102] In the training cohort (n=183), the inventors used linear discriminant analysis effect size (LEfSe) to identify disease-specific OTUs compared to healthy controls. For CHB, 60 outs were detected to be significantly increased or decreased, among which 12 OTUs were generally distributed in more than 50 samples (Table 2). Three OTUs enriched in CHB patients belonged to Clostridium XI and Megamonas, while nine OTUs enriched in healthy controls belonged to Butyricimonas , Bacteroides, Parabacteroides, Alistipes, Barnesiella and unclassified genera of Lachnopiraceae.

[0103] Table 2. Disease-specific OTUs determined by the linear discriminant analysis effect size (LEfSe) method

[0104]

[0105] The gut dysbiosis index (GDI) was calculated from the disease-specific and prevalent OTUs identified above to assess the clinical utility of such biomarkers. CHB-specific GDI in patients was sign...

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Abstract

The present invention provides a method for assessing the presence or the risk of development of liver disease or chronic hepatitis B in a subject based on OTUs enriched in CHB patients or healthy controls. Also provided is a method for monitoring response to disease treatment or diet intervention in a subject having liver disease or chronic hepatitis B based on these OTUs.

Description

Background technique [0001] Hepatitis B virus (HBV) infection is a worldwide epidemic burden, with an estimated 240 million patients living with chronic hepatitis B (CHB) disease in 2005 (1). CHB increases the risk of liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), which are estimated to cause 310,000 and 340,000 deaths globally each year, respectively (2). Systemic strategies are urgently needed to continue to monitor and prevent the progression of severe liver failure in CHB patients (3). [0002] HBV infection has been reported to be associated with dysbiosis of the gut microbiota, which includes intraportal bacterial translocation and increased endotoxin load, leading to activation of hepatic Toll-like receptors (TLRs) and NOD-like receptors (NLRs). TLR / NLR activates the host's systemic proinflammatory response by inducing signaling cascades including the nuclear factor kappa B (NF-κB) transcriptional pathway and accelerating cytokines such as tumor necrosi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6869C12Q1/689C12Q1/70
CPCC12Q1/6883C12Q1/689C12Q1/706Y02A90/10
Inventor 赵立平王景
Owner PERFECT CHINA
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