Literature DB >> 17352011

Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis.

Yusuf Yilmaz1, Enver Dolar, Engin Ulukaya, Semra Akgoz, Murat Keskin, Murat Kiyici, Sibel Aker, Arzu Yilmaztepe, Selim Gurel, Macit Gulten, Selim-Giray Nak.   

Abstract

AIM: To investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis in patients with nonalcoholic fatty liver disease (NAFLD).
METHODS: A total of 83 patients with suspected NAFLD and 49 healthy volunteers were investigated. Patients with suspected NAFLD were classified according to their liver histology into four groups: definitive NASH (n=45), borderline NASH (n=24), simple fatty liver (n=9), and normal tissue (n=5). Serum levels of caspase-3 generated cytokeratin-18 fragments (M30-antigen) and total cytokeratin-18 (M65-antigen) were determined by ELISA.
RESULTS: Levels of M30-antigen and M65-antigen were significantly higher in patients with definitive NASH compared to the other groups. An abnormal value (> 121.60 IU/L) of M30-antigen yielded a 60.0% sensitivity and a 97.4% specificity for the diagnosis of NASH. Sensitivity and specificity of an abnormal M65-antigen level (> 243.82 IU/L) for the diagnosis of NASH were 68.9% and 81.6%, respectively. Among patients with NAFLD, M30-antigen and M65-antigen levels distinguished between advanced fibrosis and early-stage fibrosis with a sensitivity of 64.7% and 70.6%, and a specificity of 77.3% and 71.2%, respectively.
CONCLUSION: Serum levels of M30-antigen and M65-antigen may be of clinical usefulness to identify patients with NASH. Further studies are mandatory to better assess the role of these apoptonecrotic biomarkers in NAFLD pathophysiology.

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Year:  2007        PMID: 17352011      PMCID: PMC4065917          DOI: 10.3748/wjg.v13.i6.837

Source DB:  PubMed          Journal:  World J Gastroenterol        ISSN: 1007-9327            Impact factor:   5.742


  36 in total

1.  In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease.

Authors:  Anna Wieckowska; Nizar N Zein; Lisa M Yerian; A Rocio Lopez; Arthur J McCullough; Ariel E Feldstein
Journal:  Hepatology       Date:  2006-07       Impact factor: 17.425

2.  Apoptosis generates stable fragments of human type I keratins.

Authors:  N O Ku; J Liao; M B Omary
Journal:  J Biol Chem       Date:  1997-12-26       Impact factor: 5.157

3.  Steatohepatitis: a tale of two "hits"?

Authors:  C P Day; O F James
Journal:  Gastroenterology       Date:  1998-04       Impact factor: 22.682

4.  Immunocytochemical detection and mapping of a cytokeratin 18 neo-epitope exposed during early apoptosis.

Authors:  M P Leers; W Kölgen; V Björklund; T Bergman; G Tribbick; B Persson; P Björklund; F C Ramaekers; B Björklund; M Nap; H Jörnvall; B Schutte
Journal:  J Pathol       Date:  1999-04       Impact factor: 7.996

5.  Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.

Authors:  C A Matteoni; Z M Younossi; T Gramlich; N Boparai; Y C Liu; A J McCullough
Journal:  Gastroenterology       Date:  1999-06       Impact factor: 22.682

Review 6.  Nonalcoholic steatohepatitis.

Authors:  S G Sheth; F D Gordon; S Chopra
Journal:  Ann Intern Med       Date:  1997-01-15       Impact factor: 25.391

7.  Sampling variability of liver biopsy in nonalcoholic fatty liver disease.

Authors:  Vlad Ratziu; Frédéric Charlotte; Agnès Heurtier; Sophie Gombert; Philippe Giral; Eric Bruckert; André Grimaldi; Frédérique Capron; Thierry Poynard
Journal:  Gastroenterology       Date:  2005-06       Impact factor: 22.682

8.  Design and validation of a histological scoring system for nonalcoholic fatty liver disease.

Authors:  David E Kleiner; Elizabeth M Brunt; Mark Van Natta; Cynthia Behling; Melissa J Contos; Oscar W Cummings; Linda D Ferrell; Yao-Chang Liu; Michael S Torbenson; Aynur Unalp-Arida; Matthew Yeh; Arthur J McCullough; Arun J Sanyal
Journal:  Hepatology       Date:  2005-06       Impact factor: 17.425

9.  The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease.

Authors:  D Sorbi; J Boynton; K D Lindor
Journal:  Am J Gastroenterol       Date:  1999-04       Impact factor: 10.864

10.  Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations.

Authors:  Z M Younossi; T Gramlich; Y C Liu; C Matteoni; M Petrelli; J Goldblum; L Rybicki; A J McCullough
Journal:  Mod Pathol       Date:  1998-06       Impact factor: 7.842

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  49 in total

1.  M-30 and 4HNE are sequestered in different aggresomes in the same hepatocytes.

Authors:  Fataneh Amidi; Barbara A French; David Chung; Charles H Halsted; Valentina Medici; Samuel W French
Journal:  Exp Mol Pathol       Date:  2007-10-25       Impact factor: 3.362

2.  A "biomarker biopsy" for the diagnosis of NASH: promises from CK-18 fragments.

Authors:  Yusuf Yilmaz; Engin Ulukaya; Enver Dolar
Journal:  Obes Surg       Date:  2008-08-05       Impact factor: 4.129

3.  Non invasive tools for the diagnosis of liver cirrhosis.

Authors:  Maurizio Soresi; Lydia Giannitrapani; Melchiorre Cervello; Anna Licata; Giuseppe Montalto
Journal:  World J Gastroenterol       Date:  2014-12-28       Impact factor: 5.742

4.  Serum immunoglobulin A concentration is a reliable biomarker for liver fibrosis in non-alcoholic fatty liver disease.

Authors:  Iradj Maleki; Mahmood Reza Aminafshari; Tarang Taghvaei; Vahid Hosseini; Alireza Rafiei; Zhila Torabizadeh; Maryam Barzin; Elahe Orang
Journal:  World J Gastroenterol       Date:  2014-09-21       Impact factor: 5.742

5.  Hepatic reticuloendothelial system cell iron deposition is associated with increased apoptosis in nonalcoholic fatty liver disease.

Authors:  Bryan D Maliken; James E Nelson; Heather M Klintworth; Mary Beauchamp; Matthew M Yeh; Kris V Kowdley
Journal:  Hepatology       Date:  2013-03-14       Impact factor: 17.425

6.  Circulating Soluble Fas and Fas Ligand Levels Are Elevated in Children with Nonalcoholic Steatohepatitis.

Authors:  Naim Alkhouri; Anna Alisi; Vera Okwu; Ammar Matloob; Federica Ferrari; Annalisa Crudele; Rita De Vito; Rocio Lopez; Ariel E Feldstein; Valerio Nobili
Journal:  Dig Dis Sci       Date:  2015-03-13       Impact factor: 3.199

Review 7.  Beyond insulin resistance: Innate immunity in nonalcoholic steatohepatitis.

Authors:  Jacquelyn J Maher; Pablo Leon; James C Ryan
Journal:  Hepatology       Date:  2008-08       Impact factor: 17.425

8.  Keratin 18 phosphorylation as a progression marker of chronic hepatitis B.

Authors:  Ying Shi; Shihui Sun; Yali Liu; Junfeng Li; Tong Zhang; Hao Wu; Xinyue Chen; Dexi Chen; Yusen Zhou
Journal:  Virol J       Date:  2010-03-24       Impact factor: 4.099

9.  A silybin-phospholipids complex counteracts rat fatty liver degeneration and mitochondrial oxidative changes.

Authors:  Ignazio Grattagliano; Catia V Diogo; Maria Mastrodonato; Ornella de Bari; Michele Persichella; David Q H Wang; Adriana Liquori; Domenico Ferri; Maria Rosaria Carratù; Paulo J Oliveira; Piero Portincasa
Journal:  World J Gastroenterol       Date:  2013-05-28       Impact factor: 5.742

Review 10.  Noninvasive diagnosis of nonalcoholic fatty liver disease: Are we there yet?

Authors:  Naim Alkhouri; Ariel E Feldstein
Journal:  Metabolism       Date:  2016-02-02       Impact factor: 8.694

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