Serum Fragmented Cytokeratin 18 Levels Reflect the Histologic Activity Score of Nonalcoholic Fatty Liver Disease More Accurately Than Serum Alanine Aminotransferase Levels

Tsutsui, Masaru; Tanaka, Naoki; Kawakubo, Masatomo; Sheena, Yo; Horiuchi, Akira; Komatsu, Michiharu; Nagaya, Tadanobu; Joshita, Satoru; Umemura, Takeji; Ichijo, Tetsuya; Matsumoto, Akihiro; Yoshizawa, Kaname; Aoyama, Toshifumi; Tanaka, Eiji; Sakai, Kenji

doi:10.1097/mcg.0b013e3181bdefe2

Cited by 71 publications

(73 citation statements)

References 38 publications

(36 reference statements)

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“…The patient selection criteria and diagnostic criteria of hepatic steatosis were the same as those in the patients who underwent PD. [9][10][11][12][13][14][15]. The diagnosis of NASH was confirmed by histological findings [13].…”

Section: Patients Who Underwent Total Gastrectomymentioning

confidence: 98%

Clinical characteristics of de novo nonalcoholic fatty liver disease following pancreaticoduodenectomy

et al. 2011

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Section: Patients Who Underwent Total Gastrectomymentioning

confidence: 98%

Clinical characteristics of de novo nonalcoholic fatty liver disease following pancreaticoduodenectomy

et al. 2011

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“…The relationship of fibrosis score with CK 18 was positive but not significant (r = +0.113, P>0.05). Tsutsui et al [15] also observed that there was no significant correlation between fibrosis and CK-18 fragment level. On the other hand, Joka et al [12] observed a positive significant correlation between CK-18 fragment level and fibrosis score12.…”

Section: Discussionmentioning

confidence: 87%

“…It reveals that serum CK-18 fragment (P=0.003) was significantly associated with the presence of NASH. Several studies also observed that serum CK-18 fragment was independently associated with NASH [1,15]. The area under the receiver-operating characteristic (ROC) curves for the diagnosis of NASH was depicted in our study.…”

Section: Discussionmentioning

confidence: 87%

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Association of Serum Cytokeratin-18 Fragment Concentration in Patients with Different Types of Nonalcoholic Fatty Liver Disease

Ahmed¹

2015

GHOA

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Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver diseases worldwide. The prevalence of NAFLD was 15% in the Asian population. In a study, NASH was observed in 42.4% of NAFLD cases in Bangladesh. It is a serious clinical problem because of its worldwide distribution and potential adverse sequel. Cytokeratin-18 fragment is a marker of hepatocyte apoptosis. Measurement of serum cytokeratin-18 fragment concentration is a noninvasive, quick and simple procedure that can be carried out easily in peripheral hospital. It can be very much helpful for early detection and frequent monitoring of disease progression and response to therapy. This cross sectional study was conducted in the Department of Clinical Pathology in collaboration with Department of Hepatology and Department of Pathology, BSMMU, Dhaka from March 2014 to February 2015. Forty patients who fulfilled the criteria of NAFLD were determined in our study. The concentration of serum CK-18 fragment was measured to evaluate its association in different types of NAFLD by enzyme linked immune sorbent assay (ELISA). In this study, we observed that the serum CK-18 fragment concentration was increased in relation to Nonalcoholic fatty liver disease Activity Score (NAS) (r=+0.7134, P<0.05). To assess diagnostic performance of CK-18 fragment were used receiver-operator characteristic (ROC) curve. The area under ROC was 0.918 for identification of NASH. Using a cutoff value of 150 U/L the sensitivity and specificity of CK-18 fragment were 85.7% and 80.8% respectively. The positive predictive value, negative predictive value and accuracy of CK-18 fragment were 66.67%, 90.91% and 80.00% respectively. Our data revealed that serum CK-18 fragment was strongly associated with Nonalcoholic fatty liver disease Activity Score (NAS). Serum CK-18 fragment may be a useful noninvasive tool for assessing NASH in patients with NAFLD.

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“…fragment is a useful biomarker to determine the degree of liver damage (Linder et al, 2010;Tsutsui et al, 2010).…”

Section: Discussion the Conserved Caspase Cleavage Site In Intermediamentioning

confidence: 99%

A mutation in keratin 18 that causes caspase-digestion resistance protects homozygous transgenic mice from hepatic apoptosis and injury

Yoon

Hong

et al. 2017

Journal of Cell Science

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Cytoskeletal keratin 18 (K18) undergoes caspase-mediated digestion during apoptosis, which leads to dramatic disassembly of keratin filaments. We studied the significance of K18 caspase digestion in a mouse model and generated transgenic mice expressing the human K18 caspase digestion-resistant double-mutant K18-D238/397E in a mouse (m) K18-null background, and compared their response to injury mediated by administration of antibody against tumor necrosis factor receptor superfamily member 6 (Fas), anti-FasAb. Notably, K18-D238/ 397E;mK18-null mice were significantly more resistant to anti-FasAbinduced injury as compared with K18-WT;mK18-null mice (23% vs 57% lethality, respectively; P<0.001). The same applied when the toxin microcystin-LR (MLR) was used to induce liver injury, i.e. lethality of K18-D238/397E;mK18-null mice in response to MLR treatment was reduced compared with the control mouse strain. The lesser rate of apoptosis in K18-D238/397E;mK18-null livers is associated with delayed degradation and, thus, sustained activation of cell-survival-related protein kinases, including stress-activated protein kinases and the NF-κB transcription factor, up to 6-8 h after administration of anti-FasAb. However, activation of the kinases and NF-κB in K18-WT-reconstituted livers decreases dramatically 8 h after anti-FasAb administration. In addition, the D238/397E double-mutation results in prolonged stability of K18 protein in transfected cells and transgenic livers. Therefore, our results show that the caspase digestion-resistant K18 helps to maintain keratin filament organization and delays apoptosis, thereby resulting in protection from liver injury.

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Serum Fragmented Cytokeratin 18 Levels Reflect the Histologic Activity Score of Nonalcoholic Fatty Liver Disease More Accurately Than Serum Alanine Aminotransferase Levels

Abstract: Background & Goals: Reliable non-invasive biomarkers to assess the histological

Cited by 71 publications

References 38 publications

Clinical characteristics of de novo nonalcoholic fatty liver disease following pancreaticoduodenectomy

Clinical characteristics of de novo nonalcoholic fatty liver disease following pancreaticoduodenectomy

Association of Serum Cytokeratin-18 Fragment Concentration in Patients with Different Types of Nonalcoholic Fatty Liver Disease

A mutation in keratin 18 that causes caspase-digestion resistance protects homozygous transgenic mice from hepatic apoptosis and injury

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