ReviewHepatology (Baltimore, Md.)2016
Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver.
Review in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Serum Cytokeratin-18 levels as a prognostic biomarker in advanced liver disease: a comprehensive meta-analysis.Clinical and experimental medicine · 2024Pooled it
- CT Radiomics to Predict Regenerative Biomarker Expression after Liver Venous Embolization: Proof-of-Concept in a Porcine Model.Journal of vascular and interventional radiology : JVIR · 2026Article
- Affinity Proteomics-Based Non-Invasive Detection of Clinically Significant Liver Disease.Alimentary pharmacology & therapeutics · 2026Observational
- Unveiling novel macrophage-specific biomarkers in MASH through single-cell sequencing for diagnostic modeling.Journal of lipid research · 2026Article
- Regulation of Keratin Chemical Modifications: Potential Molecular Mechanisms in Proliferative Diseases.International journal of molecular sciences · 2026Review
- Assessment of tissue homogenate levels of TGM1, PPL and KRT8 in a group of patients with HNSCC tumors and matched surgical margin samples.Frontiers in oncology · 2026Article
- Biomarkers for early identification of metabolic dysfunction-associated steatotic liver disease (MASLD): a narrative review.Archives of medical science : AMS · 2026Article
- Bio-Inspired Artificial Intelligence Multimorbidity Score for Human-Machine Clinical Risk Stratification.Cyborg and bionic systems (Washington, D.C.) · 2026Article
- Subclinical Hepatic Injury and Dysfunction Following Surgery: Evidence From a Young and Aged Laparotomy Murine Model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Potential amelioration of liver function by low-dose tolvaptan in heart failure patients.Toxicology reports · 2025Article
- Lipidomics-based plasma signature of alcohol-related hepatitis linked to short-term mortality.JHEP reports : innovation in hepatology · 2025Article
- Recompensation of Liver Cirrhosis by TIPS Reduces Epithelial Cell Death Markers, Translating Into Improved Clinical Outcome.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Mental Manifestations and Biomarkers of Alcohol Consumption.Life (Basel, Switzerland) · 2024Review
- High Bile Titer and High Bile to Serum Ratio of CYFRA 21 - 1 Reliably Discriminate Malignant Biliary Obstruction Caused by Cholangiocarcinoma.Journal of gastrointestinal cancer · 2024Article
- Article
- Serum/Plasma Proteome in Non-Malignant Liver Disease.International journal of molecular sciences · 2024Review
- Can serum M30 levels be utilized as an activation marker in patients with ulcerative colitis?Revista da Associacao Medica Brasileira (1992) · 2024Article
- Hepatic Macrophages as Targets for the MSC-Based Cell Therapy in Non-Alcoholic Steatohepatitis.Biomedicines · 2023Review
- The Role of Carbamoyl Phosphate Synthetase 1 as a Prognostic Biomarker in Patients With Acetaminophen-induced Acute Liver Failure.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2023Article
- Serum keratin 18-M65 levels detect progressive forms of alcohol-associated liver disease in early noncirrhotic stages.Alcohol, clinical & experimental research · 2023Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
Abstract
unlabelledKeratins, formerly known as cytokeratins, are the major epithelial-specific subgroup of intermediate filament proteins. Adult hepatocytes express keratin polypeptides 8 and 18 (K8/K18), whereas cholangiocytes express K8/K18 and keratins 7 and 19 (K7/K19). Keratins function primarily to protect hepatocytes from apoptosis and necrosis, which was revealed using several genetic mouse models. This cytoprotective function was further clarified by the identification of natural human keratin variants that are normally silent, but become pathogenic by predisposing their carriers to apoptosis during acute or chronic liver injury mediated by toxins, virus infection, or metabolic stress. During apoptosis, caspases cleave K18 and K19 at conserved aspartates (human K18/K19: (235) Val-Glu-Val-Asp(↓) ) and K18 at a unique aspartate (human K18: (394) Asp-Ala-Leu-Asp(↓) ), with the latter exposed epitope becoming recognized by the M30 antibody in blood and tissues. Additional K18-containing protein backbone epitopes are detected using the M6 and M5 (termed M65) antibodies. Intact K18 and its associated fragments, which are released into blood during apoptosis and necrosis in various diseases, have been analyzed by enzyme-linked immunosorbent assay using the M30/M65 antibodies or their signal ratios. Furthermore, M30/M65 levels have been used as diagnostic and prognostic biomarkers in acute and chronic liver diseases, including nonalcoholic steatohepatitis and acute liver failure. Other keratin biomarkers include K8/K18/K19-related tissue polypeptide antigen, K18-related tissue polypeptide-specific antigen, and K19-related CYFRA-21-1, which have been evaluated mostly in patients with epithelial tumors.
conclusionKeratins and their fragments are released into blood during liver and other epithelial tissue injury. The epithelial specificity of K18/K19, epitope unmasking upon caspase digestion, keratin abundance, and relative keratin stability render them useful biomarkers for hepatocyte and cholangiocyte apoptosis and necrosis. However, the precise biochemical nature and release mechanism of circulating keratins remain unknown. (Hepatology 2016;64:966-976).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.