RGD Reference Report - Cell death markers in patients with cirrhosis and acute decompensation. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Cell death markers in patients with cirrhosis and acute decompensation.

Authors: Macdonald, Stewart  Andreola, Fausto  Bachtiger, Patrik  Amoros, Alex  Pavesi, Marco  Mookerjee, Rajeshwar  Zheng, Yu Bao  Gronbaek, Henning  Gerbes, Alexander L  Sola, Elsa  Caraceni, Paolo  Moreau, Richard  Gines, Pere  Arroyo, Vicente  Jalan, Rajiv 
Citation: Macdonald S, etal., Hepatology. 2018 Mar;67(3):989-1002. doi: 10.1002/hep.29581. Epub 2018 Jan 24.
RGD ID: 18337484
Pubmed: PMID:29023872   (View Abstract at PubMed)
DOI: DOI:10.1002/hep.29581   (Journal Full-text)

The aims of this study were to determine the role of cell death in patients with cirrhosis and acute decompensation (AD) and acute on chronic liver failure (ACLF) using plasma-based biomarkers. The patients studied were part of the CANONIC (CLIF Acute-on-Chronic Liver Failure in Cirrhosis) study (N = 337; AD, 258; ACLF, 79); additional cohorts included healthy volunteers, stable patients with cirrhosis, and a group of 16 AD patients for histological studies. Caspase-cleaved keratin 18 (cK18) and keratin 18 (K18), which reflect apoptotic and total cell death, respectively, and cK18:K18 ratio (apoptotic index) were measured in plasma by enzyme-linked immunosorbent assay. The concentrations of cK18 and K18 increased and the cK18:K18 ratio decreased with increasing severity of AD and ACLF (P < 0.001, respectively). Alcohol etiology, no previous decompensation, and alcohol abuse were associated with increased cell death markers whereas underlying infection was not. Close correlation was observed between the cell death markers and, markers of systemic inflammation, hepatic failure, alanine aminotransferase, and bilirubin, but not with markers of extrahepatic organ injury. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining confirmed evidence of greater hepatic cell death in patients with ACLF as opposed to AD. Inclusion of cK18 and K18 improved the performance of the CLIF-C AD score in prediction of progression from AD to ACLF (P < 0.05).
CONCLUSION: Cell death, likely hepatic, is an important feature of AD and ACLF and its magnitude correlates with clinical severity. Nonapoptotic forms of cell death predominate with increasing severity of AD and ACLF. The data suggests that ACLF is a heterogeneous entity and shows that the importance of cell death in its pathophysiology is dependent on predisposing factors, precipitating illness, response to injury, and type of organ failure. (Hepatology 2018;67:989-1002).

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
liver cirrhosis severityIEP 18337484protein:increased expression: serum (human)RGD 
liver cirrhosis severityISOKRT18 (Homo sapiens)18337484; 18337484protein:increased expression: serum (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Krt18  (keratin 18)

Genes (Mus musculus)
Krt18  (keratin 18)

Genes (Homo sapiens)
KRT18  (keratin 18)


Additional Information