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Cytokeratin-18 as a noninvasive biomarker of inflammation in nonalcoholic fatty liver disease

Pavlina Boykova-Valcheva, Irina Ivanova, Yana Bocheva

Abstract

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a public health problem of global significance. It is defined as the presence of hepatic steatosis in more than 5% of hepatocytes, as determined by imaging or histological examination, in individuals consuming little or no alcohol, and in whom a secondary cause of steatosis has been excluded. Because of the proven association between NAFLD and metabolic syndrome (MetSyn), an international panel of experts has proposed to replace the term non-alcoholic fatty liver disease with the term metabolic-associated fatty liver disease (MAFLD). Nonalcoholic fatty liver disease is divided into two main groups: nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Multiple serum biomarkers have been investigated to predict the presence of NASH. Cytokeratin-18 (CK18) is the only validated biomarker. It is a marker of hepatocyte apoptosis and predicts presence of steatohepatitis.

Aim: The aim of this article is to evaluate the application of CK18 as a diagnostic marker of inflammation in NAFLD and its relevance using anthropometric parameters, routine laboratory tests, ultrasonographically defined degree of steatosis, and stage of fibrosis calculated from non-invasive scores.

Materials and Methods: The study included 61 persons with ultrasonographycally proven NAFLD (mean age 56.9 years). Data on anthropometry, clinical features, standard laboratory tests, ultrasound examination, and serum levels of total CK18, determined by the ELISA method, were collected. Using some laboratory parameters and clinical characteristics of the patients, scores for non-invasive assessment of fibrosis were calculated.

Results: Normal CK18 levels were found in 55 patients (90.17%), and an increase in CK18 above 5 ng/mL, indicating the presence of steatohepatitis, was found in 6 patients (9.83%), of which 2 males and 4 females. In CK18 levels above 5 ng/mL (ULN), we accepted a diagnosis of steatohepatitis. We found moderately strong positive correlation between the level of triglycerides and CK18, indicating an increase in the levels of triglycerides in parallel with the CK18 levels. Such correlation was not found with the increase of body mass index (BMI) and waist circumference and the increase in CK18 levels. Significantly increased AST, ALT, and GGT levels were observed in the group of patients with CK18 above 5 ng/mL, compared to the patients in the group with normal CK18. In our study, the correlation analysis between the level of CK18 and the degree of steatosis and the stage of fibrosis did not find a statistically significant correlation.

Conclusion: We assumed that the detection of elevated CK18 levels is a reliable method to prove inflammation in NAFLD.


Keywords

cytokeratin-18; non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis

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DOI: http://dx.doi.org/10.14748/ssm.v55i2.9368
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About The Authors

Pavlina Boykova-Valcheva
Medical University of Varna
Bulgaria

Clinic of Gastroenterology, St. Marina University Hospital Varna

Irina Ivanova
Medical University of Varna
Bulgaria

Clinic of Gastroenterology, St. Marina University Hospital Varna

Yana Bocheva
Medical University of Varna
Bulgaria

Clinic of Gastroenterology, St. Marina University Hospital Varna

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