Identification of Key Genes and Infiltrating Immune Cells Among Acetaminophen-induced Acute Liver Failure and HBV-associated Acute Liver Failure

Overview

Journal Ann Transl Med

Publisher AME Publishing Company

Date 2022 Aug 15

PMID 35965803

Authors

Min Shi

Zhuyi Zhou

Zhongxia Zhou

Lijuan Shen

Jianbo Shen

Guoxiong Zhou

Renfei Zhu

Affiliations

Soon will be listed here.

Abstract

Background: Acute liver failure (ALF) is a life-threatening complication that is relatively uncommon. ALF causes severe hepatocyte damage and necrosis, which can lead to liver dysfunction and even multi-organ failure. A growing body of evidence suggests that immune cell infiltration and some abnormally expressed genes are associated with ALF development. However, in ALF, they have yet to be thoroughly investigated.

Methods: The Gene Expression Omnibus (GEO) database was used to obtain microarray datasets such as GSE74000, GSE120652, GSE38941, and GSE14668, which were then examined via GEO2R to determine differentially expressed genes (DEGs) associated with ALF. Metascape was employed to annotate the underlined genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The mechanism of IGF1 in 2 different kinds of ALF including acetaminophen-induced ALF and hepatitis B virus (HBV)-induced ALF was studied using gene set enrichment analysis (GSEA). Next, immune cell infiltration was investigated and differentiated in ALF using CIBERSORT.

Results: Six genes () were found to be abnormally expressed in the 2 distinct types of ALF i.e., acetaminophen-induced ALF and HBV-induced ALF. was identified as a hub gene in ALF and was found to be associated with several developmental cascades including immune responses, inflammatory responses, and intracellular calcium homeostasis. Additionally, the number of CD4 naive T cells, CD8 T cells, and follicular helper T cells was increased in acetaminophen-induced ALF, whereas the number of activated NK cells, resting NK cells, and plasma cells was increased in HBV-induced ALF.

Conclusions: The present study determined a potential molecular target, namely , in acetaminophen-induced ALF and HBV-induced ALF, which may provide novel insights into the pathophysiology and management of ALF. Concurrently, the putative immunological pathways have been found.

Citing Articles

Integrative Analyses of Genes of Pediatric Non-alcoholic Fatty Liver Disease Associated with Energy Metabolism.

Lin Y, Ye H, Chen Y, Zhang R, Chen Y, Ou W Dig Dis Sci. 2024; 69(12):4373-4391.

PMID: 39496907 PMC: 11602812. DOI: 10.1007/s10620-024-08702-4.

Modifications of the GH Axis Reveal Unique Sexually Dimorphic Liver Signatures for , , , , .

Brie B, Sarmento-Cabral A, Pascual F, Cordoba-Chacon J, Kineman R, Becu-Villalobos D J Endocr Soc. 2024; 8(3):bvae015.

PMID: 38370444 PMC: 10872697. DOI: 10.1210/jendso/bvae015.

Metabolic Health and Disease: A Role of Osteokines?.

Shimonty A, Bonewald L, Huot J Calcif Tissue Int. 2023; 113(1):21-38.

PMID: 37193929 DOI: 10.1007/s00223-023-01093-0.

A Predictive Model to Evaluate the HbeAg Positivity of Chronic Hepatitis B Virus Patients in Clinics: A Cross-Sectional Study.

Wang N, Zheng J, Huang Y, Pu X, Jiang L, Yang J Medicina (Kaunas). 2022; 58(9).

PMID: 36143956 PMC: 9500857. DOI: 10.3390/medicina58091279.

References

Triantafyllou E, Woollard K, McPhail M, Antoniades C, Possamai L . The Role of Monocytes and Macrophages in Acute and Acute-on-Chronic Liver Failure. Front Immunol. 2019; 9:2948. PMC: 6302023. DOI: 10.3389/fimmu.2018.02948. View

Leek J, Johnson W, Parker H, Jaffe A, Storey J . The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012; 28(6):882-3. PMC: 3307112. DOI: 10.1093/bioinformatics/bts034. View

Rajaram P, Subramanian R . Acute Liver Failure. Semin Respir Crit Care Med. 2018; 39(5):513-522. DOI: 10.1055/s-0038-1673372. View

Downs I, Aw T, Liu J, Adegboyega P, Ajuebor M . Vα14iNKT cell deficiency prevents acetaminophen-induced acute liver failure by enhancing hepatic glutathione and altering APAP metabolism. Biochem Biophys Res Commun. 2012; 428(2):245-51. PMC: 3501592. DOI: 10.1016/j.bbrc.2012.10.029. View

Federico P, Petrillo A, Giordano P, Bosso D, Fabbrocini A, Ottaviano M . Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Status and Novel Perspectives. Cancers (Basel). 2020; 12(10). PMC: 7603151. DOI: 10.3390/cancers12103025. View

Gao C, Shen J, Chen W, Yao L, Liang X, Zhu R . Increased expression predicts poor prognosis in hepatocellular carcinoma based on bioinformatics. J Gastrointest Oncol. 2021; 12(4):1905-1926. PMC: 8421916. DOI: 10.21037/jgo-21-390. View

Pehrsson M, Manon-Jensen T, Sun S, Villesen I, Castane H, Joven J . An MMP-degraded and cross-linked fragment of type III collagen as a non-invasive biomarker of hepatic fibrosis resolution. Liver Int. 2022; 42(7):1605-1617. PMC: 9324161. DOI: 10.1111/liv.15270. View

Khanam A, Kottilil S . Abnormal Innate Immunity in Acute-on-Chronic Liver Failure: Immunotargets for Therapeutics. Front Immunol. 2020; 11:2013. PMC: 7578249. DOI: 10.3389/fimmu.2020.02013. View

Grek A, Arasi L . Acute Liver Failure. AACN Adv Crit Care. 2016; 27(4):420-429. DOI: 10.4037/aacnacc2016324. View

10.

Chapin C, Taylor S, Malladi P, Neighbors K, Melin-Aldana H, Kreiger P . Transcriptional Analysis of Liver Tissue Identifies Distinct Phenotypes of Indeterminate Pediatric Acute Liver Failure. Hepatol Commun. 2021; 5(8):1373-1384. PMC: 8369940. DOI: 10.1002/hep4.1726. View

11.

Nissim O, Melis M, Diaz G, Kleiner D, Tice A, Fantola G . Liver regeneration signature in hepatitis B virus (HBV)-associated acute liver failure identified by gene expression profiling. PLoS One. 2012; 7(11):e49611. PMC: 3504149. DOI: 10.1371/journal.pone.0049611. View

12.

Wu D, Zhang L, Ma S, Zhao Y, Chen R, Zhang F . Low Growth Hormone Levels Predict Poor Outcome of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure. Front Med (Lausanne). 2021; 8:655863. PMC: 8290074. DOI: 10.3389/fmed.2021.655863. View

13.

Huang C, Li Q, Huang Y, Chen L . Role of Immune Dysfunction in Acute-on-Chronic Liver Failure: From Pathogenesis to Clinical Prognosis. Discov Med. 2021; 31(162):21-29. View

14.

Lv H, Fan X, Wang L, Feng H, Ci X . Daphnetin alleviates lipopolysaccharide/d-galactosamine-induced acute liver failure via the inhibition of NLRP3, MAPK and NF-κB, and the induction of autophagy. Int J Biol Macromol. 2018; 119:240-248. DOI: 10.1016/j.ijbiomac.2018.07.101. View

15.

Stravitz R, Lee W . Acute liver failure. Lancet. 2019; 394(10201):869-881. PMC: 10836844. DOI: 10.1016/S0140-6736(19)31894-X. View

16.

Nishida N, Kudo M . Immune Phenotype and Immune Checkpoint Inhibitors for the Treatment of Human Hepatocellular Carcinoma. Cancers (Basel). 2020; 12(5). PMC: 7281618. DOI: 10.3390/cancers12051274. View

17.

Wan Z, Xie G, Wu Y, Liu F, Xin S, You S . Cytokines elevated in patients with HBV-related acute-on-chronic liver failure promote NK cell mediated cytotoxicity through TRAIL. Dig Liver Dis. 2016; 48(5):528-535. DOI: 10.1016/j.dld.2016.01.008. View

18.

Rutter K, Horvatits T, Drolz A, Roedl K, Siedler S, Kluge S . [Acute liver failure]. Med Klin Intensivmed Notfmed. 2016; 113(3):174-183. PMC: 7095899. DOI: 10.1007/s00063-016-0156-x. View

19.

Barrett T, Wilhite S, Ledoux P, Evangelista C, Kim I, Tomashevsky M . NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2012; 41(Database issue):D991-5. PMC: 3531084. DOI: 10.1093/nar/gks1193. View

20.

Behzadi P, Ranjbar R . DNA microarray technology and bioinformatic web services. Acta Microbiol Immunol Hung. 2018; 66(1):19-30. DOI: 10.1556/030.65.2018.028. View