Serum cytokeratins in alcoholic liver disease: contrasting levels of cytokeratin-18 and cytokeratin-19

Gonzalez-Quintela, Arturo; Garcı́a, Javier Garcı́a; Campos, Joaquín; Pérez, Luis Francisco; Alende, M.R.; Otero, Esteban; Abdulkader, Ihab; Tomé, Santiago

doi:10.1016/j.alcohol.2006.01.003

Cited by 50 publications

(40 citation statements)

References 16 publications

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“…The levels of cytokeratin 18 have also been studied in patients with alcoholic liver disease, patients with malignancies and compared to healthy controls. It was noted that cytokeratin 18 levels in heavy drinkers was higher than those of healthy controls and tended to be even higher than those in patients with malignancies [36]. This reveals a potential for cytokeratin 18 as a follow-up marker of liver disease progression in patients known to over consume EtOH.…”

Section: Gene Symbol Fold-changementioning

confidence: 95%

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The impact of CYP2E1 on the development of alcoholic liver disease as studied in a transgenic mouse model

Butura

Nilsson

Morgan

et al. 2009

Journal of Hepatology

103

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Section: Gene Symbol Fold-changementioning

confidence: 95%

“…Cytokeratin 8 is one of the main keratins in Mallory bodies [35,36], a characteristic feature of alcoholic liver disease and of alcoholic hepatitis. It was recently shown in vitro in Fig.…”

Section: Gene Symbol Fold-changementioning

confidence: 99%

The impact of CYP2E1 on the development of alcoholic liver disease as studied in a transgenic mouse model

Butura

Nilsson

Morgan

et al. 2009

Journal of Hepatology

103

View full text Add to dashboard Cite

“…37 However, serum keratin levels are also elevated in nonmalignant diseases thereby limiting their diagnostic specificity. For example, TPS and CYFRA 21-1 levels increase in alcoholic liver disease 38 and high TPS levels occur in patients with nonalcoholic steatohepatitis. 39 In contrast to assays that non-selectively measure released keratin fragments and intact keratins, methods that use antibodies specifically recognizing apoptotic K18 or K19 fragments but not intact keratins may hold promise.…”

Section: Serologic Testing Of Keratins and Their Fragments In Liver Dmentioning

confidence: 99%

Keratins let liver live: Mutations predispose to liver disease and crosslinking generates Mallory-Denk bodies

et al. 2007

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Keratin polypeptides 8 and 18 (K8/K18) are the cytoskeletal intermediate filament proteins of hepatocytes while K8/K18/K19 are the keratins of hepatobiliary ductal cells. Hepatocyte K8/K18 are highly abundant and behave as stress proteins with injury-inducible expression. Human association studies show that K8/K18 germline heterozygous mutations predispose to end-stage liver disease of multiple etiologies (Ϸ3 fold increased risk), and to liver disease progression in patients with chronic hepatitis C infection. These findings are supported by extensive transgenic mouse and ex vivo primary hepatocyte culture studies showing that K8 or K18 mutations predispose the liver to acute or subacute injury and promote apoptosis and fibrosis. Mutation-associated predisposition to liver injury is likely related to mechanical and nonmechanical keratin functions including maintenance of cell integrity, protection from apoptosis and oxidative injury, serving as a phosphate sponge, regulation of mitochondrial organization/function and protein targeting. These functions are altered by mutationinduced changes in keratin phosphorylation, solubility and filament organization/reorganization. Keratins are also the major constituents of Mallory-Denk bodies (MDBs). A toxin-induced K8>K18 ratio, and keratin crosslinking by transglutaminase-2 play essential roles in MDB formation. Furthermore, intracellular or cell-released K18 fragments, generated by caspase-mediated proteolysis during apoptosis serve as markers of liver injury. Therefore, K8 and K18 are cytoprotective stress proteins that play a central role in guarding hepatocytes from apoptosis. Keratin involvement in liver disease is multi-faceted and includes modulating disease progression upon mutation, formation of MDBs in response to unique forms of injury, and serving as markers of epithelial cell death. (HEPATOLOGY 2007; 46:1639-1649.)

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“…Two additional patients in the same series showing bland cirrhosis (without alcoholic hepatitis) were not included in the study. All patients were included in one of three previous studies [14,17,18]. Median age of participants was 45 (range 28-74) years.…”

Section: Study Populationmentioning

confidence: 99%

“…Moreover, serum TPS levels may help differentiate nonalcoholic steatohepatitis from simple fatty liver [15]. Likewise, serum TPS concentrations may be of help in diagnosing alcoholic hepatitis [14,[16][17][18]. Furthermore, the diagnostic accuracy of serum TPS for differentiating alcoholic hepatitis from fatty liver may be higher than that of routine liver markers [16].…”

Section: Introductionmentioning

confidence: 99%

Serum Levels of Keratin-18 Fragments [Tissue Polypeptide-Specific Antigen (TPS)] Are Correlated with Hepatocyte Apoptosis in Alcoholic Hepatitis

et al. 2008

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Apoptosis is a major feature in alcoholic hepatitis. During apoptosis, the M30 neoepitope becomes exposed after keratin-18 cleavage. The tissue polypeptide-specific antigen (TPS) is a keratin-18 fragment that is routinely used as a tumor marker. Serum TPS levels are increased in patients with alcoholic hepatitis. The aim of this study was to investigate the possible relationship of TPS levels with hepatocyte apoptosis in alcoholic hepatitis. Thirty-one patients with alcoholic hepatitis and 22 with fatty liver were included. Hepatocyte apoptosis was evaluated by M30 immunostaining. Serum TPS levels were measured by a commercial immunoassay. The apoptotic score was higher in patients with alcoholic hepatitis than in patients with fatty liver. There was a significant correlation between the apoptotic score and TPS levels. The correlation of the apoptotic score with TPS levels was stronger than with standard liver tests. Serum TPS may be a marker of apoptosis in alcoholic hepatitis.

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Serum cytokeratins in alcoholic liver disease: contrasting levels of cytokeratin-18 and cytokeratin-19

Cited by 50 publications

References 16 publications

The impact of CYP2E1 on the development of alcoholic liver disease as studied in a transgenic mouse model

The impact of CYP2E1 on the development of alcoholic liver disease as studied in a transgenic mouse model

Keratins let liver live: Mutations predispose to liver disease and crosslinking generates Mallory-Denk bodies

Serum Levels of Keratin-18 Fragments [Tissue Polypeptide-Specific Antigen (TPS)] Are Correlated with Hepatocyte Apoptosis in Alcoholic Hepatitis

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