ArticleHepatology (Baltimore, Md.)2009
Keratin variants are overrepresented in primary biliary cirrhosis and associate with disease severity.
Article in Hepatology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Machine Learning Predicts Treatment Response and Prognostic Pathways From Whole-Blood Transcriptome in Primary Biliary Cholangitis.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- The relationship between keratin 18 and epithelial-derived tumors: as a diagnostic marker, prognostic marker, and its role in tumorigenesis.Frontiers in oncology · 2024Review
- Revealing the Roles of Keratin 8/18-Associated Signaling Proteins Involved in the Development of Hepatocellular Carcinoma.International journal of molecular sciences · 2021Review
- Liver disease-associated keratin 8 and 18 mutations modulate keratin acetylation and methylation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Plasma Levels of K18 Fragments Do Not Correlate with Alcoholic Liver Fibrosis.Gut and liver · 2019Article
- Intermediate filament proteins of digestive organs: physiology and pathophysiology.American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver.Hepatology (Baltimore, Md.) · 2016Review
- Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity.Clinical reviews in allergy & immunology · 2016Review
- Absence of keratin 8 or 18 promotes antimitochondrial autoantibody formation in aging male mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Human keratin 8 variants promote mouse acetaminophen hepatotoxicity coupled with c-jun amino-terminal kinase activation and protein adduct formation.Hepatology (Baltimore, Md.) · 2015Article
- Prevalence of genetic variants of keratins 8 and 18 in patients with drug-induced liver injury.BMC medicine · 2015Article
- Epiplakin attenuates experimental mouse liver injury by chaperoning keratin reorganization.Journal of hepatology · 2015Article
- Cytokeratins in gastroenterology. Systematic review.Przeglad gastroenterologiczny · 2015Review
- Genetic polymorphisms of OCT-1 confer susceptibility to severe progression of primary biliary cirrhosis in Japanese patients.Journal of gastroenterology · 2014Article
- Cytokeratin 8 is increased in hepatitis C virus cells and its ectopic expression induces apoptosis of SMMC7721 cells.World journal of gastroenterology · 2013Article
- The genetics of complex cholestatic disorders.Gastroenterology · 2013Review
- Keratin 8 variants are infrequent in patients with alcohol-related liver cirrhosis and do not associate with development of hepatocellular carcinoma.BMC gastroenterology · 2012Article
- The relevance of liver histology to predicting clinically meaningful outcomes in nonalcoholic steatohepatitis.Clinics in liver disease · 2012Review
- Keratin 8 variants are associated with cryptogenic hepatitis.Virchows Archiv : an international journal of pathology · 2012Article
- Non-coding keratin variants associate with liver fibrosis progression in patients with hemochromatosis.PloS one · 2012Article
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Authors and funding
12 authors at 7 institutions in 4 countries.
Funding
Abstract
unlabelledKeratins (K) 8 and 18 variants predispose carriers to the development of end-stage liver disease and patients with chronic hepatitis C to disease progression. Hepatocytes express K8/K18, whereas biliary epithelia express K8/K18/K19. K8-null mice, which are predisposed to liver injury, spontaneously develop anti-mitochondrial antibodies (AMA) and have altered hepatocyte mitochondrial size and function. There is no known association of K19 with human disease and no known association of K8/K18/K19 with human autoimmune liver disease. We tested the hypothesis that K8/K18/K19 variants associate with primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterized by the presence of serum AMA. In doing so, we analyzed the entire exonic regions of K8/K18/K19 in 201 Italian patients and 200 control blood bank donors. Five disease-associated keratin heterozygous variants were identified in patients versus controls (K8 G62C/R341H/V380I, K18 R411H, and K19 G17S). Four variants were novel and included K19 G17S/V229M/N184N and K18 R411H. Overall, heterozygous disease-associated keratin variants were found in 17 of 201 (8.5%) PBC patients and 4 of 200 (2%) blood bank donors (P < 0.004, odds ratio = 4.53, 95% confidence interval = 1.5-13.7). Of the K19 variants, K19 G17S was found in three patients but not in controls and all K8 R341H (eight patients and three controls) associated with concurrent presence of the previously described intronic K8 IVS7+10delC deletion. Notably, keratin variants associated with disease severity (12.4% variants in Ludwig stage III/IV versus 4.2% in stages I/II; P < 0.04, odds ratio = 3.25, 95% confidence interval = 1.02-10.40), but not with the presence of AMA.
conclusionK8/K18/K19 variants are overrepresented in Italian PBC patients and associate with liver disease progression. Therefore, we hypothesize that K8/K18/K19 variants may serve as genetic modifiers in PBC.
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