Table_2_Identification of Immune Microenvironment Changes and the Expression of Immune-Related Genes in Liver Cirrhosis.xlsx

Liver inflammation and the immune response have been recognized as critical contributors to cirrhosis pathogenesis. Immunity-related genes (IRGs) play an essential role in immune cell infiltration and immune reactions; however, the changes in the immune microenvironment and the expression of IRGs involved in cirrhosis remain unclear. CD45+ liver cell single-cell RNA (scRNA) sequencing data (GSE136103) from patients with cirrhosis were analyzed. The clusters were identified as known cell types through marker genes according to previous studies. GO and KEGG analyses among differentially expressed genes (DEGs) were performed. DEGs were screened to identify IRGs based on the ImmPort database. The protein-protein interaction (PPI) network of IRGs was generated using the STRING database. IRGs activity was calculated using the AUCell package. RNA microarray expression data (GSE45050) of cirrhosis were analyzed to confirm common IRGs and IRGs activity. Relevant regulatory transcription factors (TFs) were identified from the Human TFDB database. A total of ten clusters were obtained. CD8+ T cells and NK cells were significantly decreased in patients with cirrhosis, while CD4+ T memory cells were increased. Enrichment analyses showed that the DEGs focused on the regulation of immune cell activation and differentiation, NK-cell mediated cytotoxicity, and antigen processing and presentation. Four common TFs, IRF8, NR4A2, IKZF3, and REL were expressed in both the NK cluster and the DEGs of liver tissues. In conclusion, we proposed that the reduction of the CD8+ T cell cluster and NK cells, as well as the infiltration of CD4+ memory T cells, contributed to immune microenvironment changes in cirrhosis. IRF8, NR4A2, IKZF3, and REL may be involved in the transcriptional regulation of NK cells in liver fibrosis. The identified DEGs, IRGs, and pathways may serve critical roles in the development and progression of liver fibrosis.</p

Test of IL28B Polymorphisms in Chronic Hepatitis C Patients Treated with PegIFN and Ribavirin Depends on HCV Genotypes: Results from a Meta-Analysis

<div><h3>Background</h3><p>Many studies have been published on the association between single nucleotide polymorphisms (SNP) near the IL28B gene and response to the combined treatments of pegylated-interferon (PegIFN) and ribavirin (RBV) in chronic HCV-infected patients, but without identical conclusions. The aim of this study was to assess impact of the IL28B polymorphisms on the effect of HCV standard treatment using meta-analysis based method.</p> <h3>Methods</h3><p>Association studies between polymorphisms of rs12979860 or rs8099917 and response to PegIFN/RBV treatment in chronic HCV patients were retrieved from PubMed. Data of qualified studies on sustained virological response (SVR) in different genotypes were extracted and analyzed using meta-analysis method in Stata 10 software.</p> <h3>Results</h3><p>Thirty-four papers, containing 46 independent studies, were included in the analysis. In the HCV G1/4 patients without treatment history, individuals carrying rs12979860 CC genotype were more likely to achieve SVR (OR 3.97, 95%CI 3.29–4.80) compared to those carrying CT/TT genotypes. Similar results were observed in the HCV G1/4 patients with unsuccessful or unknown treatment history (OR 3.76, 95%CI 2.67–5.28) or in the patients co-infected with human immunodeficiency virus (OR 5.20, 95%CI 3.04–8.90). However, associations could not be observed in HCV G2/3 patients. For rs8099917, similar results were obtained for genotype TT compared to genotypes TG/GG, indicating that TT genotype was significantly associated with better treatment response in patients infected with genotype 1 or 4 HCV, but not genotype 2 or 3 HCV.</p> <h3>Conclusion</h3><p>Polymorphisms of rs12979860 and rs8099917 near IL28B only associate with the treatment response to PegIFN/RBV in patients infected with HCV genotype 1 or 4 but not with genotype 2 or 3, irrespective of the previous treatment history or HIV co-infected status. Therefore, identification of IL28B genotypes is necessary only in patients infected with relatively difficult-to-treat genotype 1 or 4 HCV.</p> </div

Forrest plot for association between rs12979860 polymorphisms and response to PegIFN/RBV in HIV co-infected patients.

<p>Forrest plot for association between rs12979860 polymorphisms and response to PegIFN/RBV in HIV co-infected patients.</p

SVR rates and frequency for rs12979860 genotypes in Caucasian treatment-naïve patients with complete data.

<p>SVR rates and frequency for rs12979860 genotypes in Caucasian treatment-naïve patients with complete data.</p

Table_3_Identification of Immune Microenvironment Changes and the Expression of Immune-Related Genes in Liver Cirrhosis.xlsx

Liver inflammation and the immune response have been recognized as critical contributors to cirrhosis pathogenesis. Immunity-related genes (IRGs) play an essential role in immune cell infiltration and immune reactions; however, the changes in the immune microenvironment and the expression of IRGs involved in cirrhosis remain unclear. CD45+ liver cell single-cell RNA (scRNA) sequencing data (GSE136103) from patients with cirrhosis were analyzed. The clusters were identified as known cell types through marker genes according to previous studies. GO and KEGG analyses among differentially expressed genes (DEGs) were performed. DEGs were screened to identify IRGs based on the ImmPort database. The protein-protein interaction (PPI) network of IRGs was generated using the STRING database. IRGs activity was calculated using the AUCell package. RNA microarray expression data (GSE45050) of cirrhosis were analyzed to confirm common IRGs and IRGs activity. Relevant regulatory transcription factors (TFs) were identified from the Human TFDB database. A total of ten clusters were obtained. CD8+ T cells and NK cells were significantly decreased in patients with cirrhosis, while CD4+ T memory cells were increased. Enrichment analyses showed that the DEGs focused on the regulation of immune cell activation and differentiation, NK-cell mediated cytotoxicity, and antigen processing and presentation. Four common TFs, IRF8, NR4A2, IKZF3, and REL were expressed in both the NK cluster and the DEGs of liver tissues. In conclusion, we proposed that the reduction of the CD8+ T cell cluster and NK cells, as well as the infiltration of CD4+ memory T cells, contributed to immune microenvironment changes in cirrhosis. IRF8, NR4A2, IKZF3, and REL may be involved in the transcriptional regulation of NK cells in liver fibrosis. The identified DEGs, IRGs, and pathways may serve critical roles in the development and progression of liver fibrosis.</p

Information of studies included in the Meta-analysis.

<p>Age were described as</p>a<p>mean ± standard deviation,</p>b<p>median (interquartile range),</p>c<p>median (range) and</p>d<p>mean age.</p><p>N/A: not available.</p

Image_2_Identification of Immune Microenvironment Changes and the Expression of Immune-Related Genes in Liver Cirrhosis.jpeg

Liver inflammation and the immune response have been recognized as critical contributors to cirrhosis pathogenesis. Immunity-related genes (IRGs) play an essential role in immune cell infiltration and immune reactions; however, the changes in the immune microenvironment and the expression of IRGs involved in cirrhosis remain unclear. CD45+ liver cell single-cell RNA (scRNA) sequencing data (GSE136103) from patients with cirrhosis were analyzed. The clusters were identified as known cell types through marker genes according to previous studies. GO and KEGG analyses among differentially expressed genes (DEGs) were performed. DEGs were screened to identify IRGs based on the ImmPort database. The protein-protein interaction (PPI) network of IRGs was generated using the STRING database. IRGs activity was calculated using the AUCell package. RNA microarray expression data (GSE45050) of cirrhosis were analyzed to confirm common IRGs and IRGs activity. Relevant regulatory transcription factors (TFs) were identified from the Human TFDB database. A total of ten clusters were obtained. CD8+ T cells and NK cells were significantly decreased in patients with cirrhosis, while CD4+ T memory cells were increased. Enrichment analyses showed that the DEGs focused on the regulation of immune cell activation and differentiation, NK-cell mediated cytotoxicity, and antigen processing and presentation. Four common TFs, IRF8, NR4A2, IKZF3, and REL were expressed in both the NK cluster and the DEGs of liver tissues. In conclusion, we proposed that the reduction of the CD8+ T cell cluster and NK cells, as well as the infiltration of CD4+ memory T cells, contributed to immune microenvironment changes in cirrhosis. IRF8, NR4A2, IKZF3, and REL may be involved in the transcriptional regulation of NK cells in liver fibrosis. The identified DEGs, IRGs, and pathways may serve critical roles in the development and progression of liver fibrosis.</p

Forrest plots for association between polymorphisms and response to PegIFN/RBV in treatment-naïve HCV G2/3 patients.

<p>A. rs12979860 (CC vs CT/TT). B. rs8099917 (TT vs TG/GG).</p

Additional file 2 of The assessment of mesenchymal stem cells therapy in acute on chronic liver failure and chronic liver disease: a systematic review and meta-analysis of randomized controlled clinical trials

Additional file 2: Figure S1. Funnel plots of MELD score at 24 weeks; ALB levels at 12 weeks, 24 weeks, and 48 weeks; TBIL at 4 weeks and 24 weeks; No asymmetry was observed in the funnel plots. No publication bias was found using Egger’s and Begg’s test

Table_1_Identification of Immune Microenvironment Changes and the Expression of Immune-Related Genes in Liver Cirrhosis.xlsx

Liver inflammation and the immune response have been recognized as critical contributors to cirrhosis pathogenesis. Immunity-related genes (IRGs) play an essential role in immune cell infiltration and immune reactions; however, the changes in the immune microenvironment and the expression of IRGs involved in cirrhosis remain unclear. CD45+ liver cell single-cell RNA (scRNA) sequencing data (GSE136103) from patients with cirrhosis were analyzed. The clusters were identified as known cell types through marker genes according to previous studies. GO and KEGG analyses among differentially expressed genes (DEGs) were performed. DEGs were screened to identify IRGs based on the ImmPort database. The protein-protein interaction (PPI) network of IRGs was generated using the STRING database. IRGs activity was calculated using the AUCell package. RNA microarray expression data (GSE45050) of cirrhosis were analyzed to confirm common IRGs and IRGs activity. Relevant regulatory transcription factors (TFs) were identified from the Human TFDB database. A total of ten clusters were obtained. CD8+ T cells and NK cells were significantly decreased in patients with cirrhosis, while CD4+ T memory cells were increased. Enrichment analyses showed that the DEGs focused on the regulation of immune cell activation and differentiation, NK-cell mediated cytotoxicity, and antigen processing and presentation. Four common TFs, IRF8, NR4A2, IKZF3, and REL were expressed in both the NK cluster and the DEGs of liver tissues. In conclusion, we proposed that the reduction of the CD8+ T cell cluster and NK cells, as well as the infiltration of CD4+ memory T cells, contributed to immune microenvironment changes in cirrhosis. IRF8, NR4A2, IKZF3, and REL may be involved in the transcriptional regulation of NK cells in liver fibrosis. The identified DEGs, IRGs, and pathways may serve critical roles in the development and progression of liver fibrosis.</p