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. 2023 Jul 6;24(13):11146.
doi: 10.3390/ijms241311146.

System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis

Vishal S Patil  1   2 , Darasaguppe R Harish  1 , Ganesh H Sampat  1   2 , Subarna Roy  1 , Sunil S Jalalpure  2 , Pukar Khanal  2 , Swarup S Gujarathi  1   2 , Harsha V Hegde  1
Affiliations

System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis

Vishal S Patil et al. Int J Mol Sci. .

Abstract

Hepatitis B infection caused by the hepatitis B virus is a life-threatening cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Researchers have produced multiple in vivo models for hepatitis B virus (HBV) and, currently, there are no specific laboratory animal models available to study HBV pathogenesis or immune response; nonetheless, their limitations prevent them from being used to study HBV pathogenesis, immune response, or therapeutic methods because HBV can only infect humans and chimpanzees. The current study is the first of its kind to identify a suitable chemically induced liver cirrhosis/HCC model that parallels HBV pathophysiology. Initially, data from the peer-reviewed literature and the GeneCards database were compiled to identify the genes that HBV and seven drugs (acetaminophen, isoniazid, alcohol, D-galactosamine, lipopolysaccharide, thioacetamide, and rifampicin) regulate. Functional enrichment analysis was performed in the STRING server. The network HBV/Chemical, genes, and pathways were constructed by Cytoscape 3.6.1. About 1546 genes were modulated by HBV, of which 25.2% and 17.6% of the genes were common for alcohol and lipopolysaccharide-induced hepatitis. In accordance with the enrichment analysis, HBV activates the signaling pathways for apoptosis, cell cycle, PI3K-Akt, TNF, JAK-STAT, MAPK, chemokines, NF-kappa B, and TGF-beta. In addition, alcohol and lipopolysaccharide significantly activated these pathways more than other chemicals, with higher gene counts and lower FDR scores. In conclusion, alcohol-induced hepatitis could be a suitable model to study chronic HBV infection and lipopolysaccharide-induced hepatitis for an acute inflammatory response to HBV.

Keywords: alcohol; hepatitis B; hepatocellular carcinoma; lipopolysaccharide; network pharmacology; rodent model.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Workflow of the current study.
Figure 2
Figure 2
The genes common in both the literature review and GeneCards for (a) HBV, (b) acetaminophen, (c) isoniazid, (d) alcohol, (e) D-galactosamine, (f) lipopolysaccharide, (g) thioacetamide, and (h) rifampicin.
Figure 3
Figure 3
Common genes between HBV (a) acetaminophen, (b) isoniazid, (c) alcohol, (d) D-galactosamine, (e) lipopolysaccharide, (f) thioacetamide, and (g) rifampicin.
Figure 4
Figure 4
Network representation of HBV-modulated genes and pathways.
Figure 5
Figure 5
Network representation of lipopolysaccharide-modulated genes and pathways.
Figure 6
Figure 6
Network representation of alcohol-modulated genes and pathways.
Figure 7
Figure 7
Molecular pathways triggered by alcohol and LPS resembled the HBV pathogenesis. The figure information is retrieved from the KEGG database “Hepatitis B: hsa05161”.
See this image and copyright information in PMC

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