Acute liver failure is associated with altered cerebral expression profiles of long non-coding RNAs

Hepatitis B virus (HBV) infection is a major cause of acute liver failure (ALF) in China, and mortality rates are high among patients who do not receive a matched liver transplant. This study aimed to determine potential mechanisms involved in HBV-ALF pathogenesis. Gene expression profiles under access numbers GSE38941 and GSE14668 were downloaded from the Gene Expression Omnibus database, including cohorts of HBV-ALF liver tissue and normal samples. Differentially expressed genes (DEGs) with false discovery rates (FDR) <0.05 and |log2(fold change)| >1 as thresholds were screened using the Limma package. Gene modules associated with stable disease were mined using weighed gene co-expression network analysis (WGCNA). A co-expression network was constructed and DEGs were analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A gene-based network was constructed to explore major factors associated with disease progression. We identified 2238 overlapping DEGs as crucial gene cohorts in ALF development. Based on a WGCNA algorithm, 10 modules (modules 1-10) were obtained that ranged from 75 to 1078 genes per module. Cyclin-dependent kinase 1 ( CDK1), cyclin B1 ( CCNB1), and cell-division cycle protein 20 ( CDC20) hub genes were screened using the co-expression network. Furthermore, 17 GO terms and 6 KEGG pathways were identified, such as cell division, immune response process, and antigen processing and presentation. Two overlapping signaling pathways that are crucial factors in HBV-ALF were screened using the Comprehensive Toxicogenomics Database (CTD). Several candidate genes including HLA-E, B2M, HLA-DPA1, and SYK were associated with HBV-ALF progression. Natural killer cell-mediated cytotoxicity and antigen presentation contributed to the progression of HBV-ALF. The HLA-E, B2M, HLA-DPA1, and SYK genes play critical roles in the pathogenesis and development of HBV-ALF.

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Erratum to: Acute liver failure-induced hepatic encephalopathy is associated with changes in microRNA expression profiles in cerebral cortex of the mouse

Metabolic Brain Disease ◽

10.1007/s11011-014-9644-y ◽

2014 ◽

Vol 30 (1) ◽

pp. 247-247 ◽

Cited By ~ 1

Author(s):

Raghu Vemuganti ◽

Vinícius R. Silva ◽

Suresh L. Mehta ◽

Alan S. Hazell

Keyword(s):

Cerebral Cortex ◽

Hepatic Encephalopathy ◽

Liver Failure ◽

Acute Liver Failure ◽

Expression Profiles ◽

Microrna Expression

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Acute liver failure-induced hepatic encephalopathy is associated with changes in microRNA expression profiles in cerebral cortex of the rat

Metabolic Brain Disease ◽

10.1007/s11011-014-9545-0 ◽

2014 ◽

Vol 29 (4) ◽

pp. 891-899 ◽

Cited By ~ 6

Author(s):

Raghu Vemuganti ◽

Vinícius R. Silva ◽

Suresh L. Mehta ◽

Alan S. Hazell

Keyword(s):

Cerebral Cortex ◽

Hepatic Encephalopathy ◽

Liver Failure ◽

Acute Liver Failure ◽

Expression Profiles ◽

Microrna Expression

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Identification and validation of circulating miRNAs as potential new biomarkers for severe liver disease in patients with leptospirosis

PLoS ONE ◽

10.1371/journal.pone.0257805 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0257805

Author(s):

Natthaya Chuaypen ◽

Umaporn Limothai ◽

Pattapon Kunadirek ◽

Pornchai Kaewsapsak ◽

Patipark Kueanjinda ◽

...

Keyword(s):

Overall Survival ◽

Liver Failure ◽

Acute Liver Failure ◽

Expression Profiles ◽

Clinical Manifestations ◽

High Sensitivity ◽

Liver Involvement ◽

Severe Liver ◽

Serum Samples ◽

Poor Overall Survival

Background Leptospirosis, a global zoonotic infectious disease, has various clinical manifestations ranging from mild self-limiting illness to life-threatening with multi-organ damage, including liver involvement. This study was aimed at identifying circulating microRNAs (miRNAs) as novel biomarkers for predicting severe liver involvement in patients with leptospirosis. Methods In a discovery set, 12 serum samples of patients with anicteric and icteric leptospirosis at initial clinical presentation were used for miRNA profiling by a NanoString nCounter miRNA assay. In a validated cohort, top candidate miRNAs were selected and further tested by qRT-PCR in serum samples of 81 and 16 individuals with anicteric and icteric leptospirosis, respectively. Results The discovery set identified 38 significantly differential expression miRNAs between the two groups. Among these, miR-601 and miR-630 were selected as the top two candidates significantly up-regulated expressed in the icteric group. The enriched KEGG pathway showed that these miRNAs were mainly involved in immune responses and inflammation. In the validated cohort, miR-601 and miR-630 levels were significantly higher in the icteric group compared with the anicteric group. Additionally, these two miRNAs displayed good predictors of subsequent acute liver failure with a high sensitivity of 100%. On regression analysis, elevated miR-601 and miR-630 expression were also predictive of multi-organ failures and poor overall survival. Conclusion Our data indicated that miRNA expression profiles were significantly differentiated between the icteric and anicteric groups. Serum miR-601 and miR-630 at presentation could potentially serve as promising biomarkers for predicting subsequent acute liver failure and overall survival in patients with leptospirosis.

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