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Evaluation of the diagnostic value of serum and tissue apoptotic cytokeratin-18 in patients with chronic hepatitis C
Authors:Hanan Abdel Haleem  Naglaa Zayed  Hanan Abdel Hafez  Ahmed Fouad  Maha Akl  Mona Hassan  Olfat Hammam  Abdellah Morsy  Azza Saleh  Moataz Seyam  Zeinab Zakaria  Soher Zakaria
Institution:1. Division of Nephrology, Departments of Medicine and Pathology, University of Washington, Seattle, Washington, USA;2. Research and Development, Biogen Idec, Cambridge, Massachusetts, USA;3. Department of Medicine, Division of Nephrology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA;4. Kidney Research Institute, University of Washington, Seattle, Washington, USA;5. Institute of Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, USA;1. Institute of Molecular and Chemical Biology, East China Normal University, Shanghai, China;2. CAS-MPG Partner Institute and Key Lab for Computational Biology, SIBS, CAS, Shanghai, China
Abstract:Background and study aimsHepatitis C virus (HCV) is considered the most common aetiology of chronic liver disease (CLD) in Egypt. The disease severity ranges from mild illness to cirrhosis and hepatocellular carcinoma. A role for apoptosis in liver damage caused by HCV chronic infection has been suggested. Cytokeratin 18 (CK-18) is the major intermediate filament protein in the liver and is a known caspase substrate in hepatocyte apoptosis. Therefore, we analysed the serum and tissue levels of CK-18 in patients with chronic HCV infection to evaluate its role in hepatocyte apoptosis. We also correlated CK-18 expression with the severity of hepatic pathology.Patients and methodsThis study examined 80 Egyptian patients with liver disease. There were 69 patients with chronic hepatitis C and 11 patients with hepatitis C-induced cirrhotic changes. Fifteen healthy controls were also included in the study. The levels of CK-18 fragment were quantified in paired serum and liver biopsy samples.ResultsThe serum and tissue CK-18 levels were reduced in chronic HCV patients compared to early cirrhosis patients. This result indicates that serum levels of CK-18 and the hepatic expression of CK-18 might play an important role in disease progression. The serum and tissue levels of CK-18 were significantly increased and directly correlated with inflammation severity, stage of fibrosis, and ALT levels in the chronic HCV group and the cirrhotic liver group. There was no significant difference in viral load between patient cohorts.ConclusionThe serum level and the hepatic expression of CK-18 are related to disease activity and are directly correlated with METAVIR scoring. This result suggests that serum CK-18 levels may be useful for monitoring disease activity in chronic HCV and liver cirrhosis patients.
Keywords:Hepatitis C virus (HCV)  Chronic liver disease (CLD)  Liver cirrhosis (LC)  Apoptosis  Cytokeratin 18 (CK-18)
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