title: Keratins:  markers and modulators of liver disease.
abstract: OBJECTIVE
  Keratins are a subgroup of intermediate filaments expressed in the epithelia. Keratins emerged as important tissue-protecting genes and keratin variants cause/predispose to development of more than 50 human disorders. Our review focuses on the importance of keratins in context of liver disease.
  
  
  RESULTS
  K8/K18 variants are found in approximately 4% of white population and predispose to development and adverse outcome of multiple liver diseases. K8/K18 are major constituents of Mallory-Denk bodies, that is inclusions found in alcoholic and nonalcoholic steatohepatitis (NASH) and dysregulated keratin expression, K8 hyperphosphorylation, misfolding and crosslinking via transglutaminase 2 facilitate aggregate formation. Necrosis-generated and apoptosis-generated keratin serum fragments are emerging as important noninvasive markers of multiple liver diseases, particularly NASH. Keratins are established markers of tumor origin and in hepatocellular carcinoma, K19 expression is associated with poor prognosis.
  
  
  CONCLUSIONS
  Keratins are established tumor markers and are widely used as noninvasive markers of liver injury. In addition, the data that have become available in recent years have greatly advanced our understanding of keratins as modifiers of liver disease development.
authors.affiliation: Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany. pavel.strnad@uniklinik-ulm.de
authors.forename: Pavel
authors.initials: P
authors.lastname: Strnad
authors.forename: Stephan
authors.initials: S
authors.lastname: Paschke
authors.forename: Kwi-Hoon
authors.initials: KH
authors.lastname: Jang
authors.forename: Nam-On
authors.initials: NO
authors.lastname: Ku
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000235:genetics / Q000378:metabolism*; D053533:Keratin-8 / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male
chemical_list: D015415:Biomarkers; D053538:Keratin-18; D053533:Keratin-8