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However, the prevalence, genetic background and factors determining the development of HBV\u2010related ALF are rarely studied. In this study, we examined three Gene Expression Omnibus (GEO) data sets by bioinformatics analysis to identify differentially expressed genes (DEGs), key biological processes and pathways. Immune infiltration analysis showed high immune cells infiltration in HBV\u2010related ALF tissue. We then confirmed natural killer cells and macrophages infiltration in clinical samples by immunohistochemistry assay, implying these cells play a significant role in HBV\u2010ALF. We found 1277 genes were co\u2010up\u2010regulated and that 1082 genes were co\u2010down\u2010regulated in the 3 data sets. Inflammation\u2010related pathways were enriched in the co\u2010up\u2010regulated genes and synthetic metabolic pathways were enriched in the co\u2010down\u2010regulated genes. WGCNA also revealed a key module enriching in immune inflammation response and identified 10 hub genes, differentially expressed in an independent data set. In conclusion, we identified fierce immune inflammatory response to elucidate the immune\u2010driven mechanism of HBV\u2010ALF and 10 hub genes based on gene expression profiles.<\/jats:p>","DOI":"10.1111\/jcmm.15561","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T04:22:40Z","timestamp":1595218960000},"page":"9798-9809","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Systematic analysis on multiple Gene Expression Omnibus data sets reveals fierce immune response in hepatitis B virus\u2010related acute liver failure"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1192-1131","authenticated-orcid":false,"given":"Huadi","family":"Chen","sequence":"first","affiliation":[{"name":"Organ Transplant Center, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Organ Donation and 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