The cytokeratin-18 fragment level as a biomarker of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus

Miyasato, Mai; Murase-Mishiba, Yuko; Bessho, Megumi; Miyawaki, Masahiro; Imbe, Hisashi; Tsutsumi, Chiharu; Tanimoto, Keiji; Imagawa, Akihisa; Terasaki, Jungo; Hanafusa, Toshiaki

doi:10.1016/j.cca.2014.03.018

Cited by 19 publications

(14 citation statements)

References 38 publications

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“…Previous efforts have been made to discover novel biomarkers or test panels to better distinguish NASH from simple steatosis. Some studies have suggested that measurement of serum CK18-M30 levels may be useful,26 27 although one study has concluded that CK18-M30 measurement alone lacked sufficient sensitivity for diagnosing NASH 28. Similarly, in the present study, we found that a substantial number of patients with persistent nALT (53 out of 105) had NASH on histology, and more importantly serum CK18-M30 levels alone did not have sufficiently high diagnostic accuracy for identifying NASH in this group of patients.…”

Section: Discussioncontrasting

confidence: 69%

“…Since it is known that most of the available non-invasive tests/methods perform poorly in diagnosing NASH, better non-invasive tests are increasingly needed, especially for screening the subgroup of patients with NAFLD with nALT levels, who may be otherwise misdiagnosed as having less harmful disease by non-specialists. In this regard, serum CK18-M30 levels and other non-invasive clinical scoring systems have been previously investigated for their ability to accurately identify NASH in patients with NAFLD and abnALT 27 38. However, these non-invasive clinical scoring systems are complex combinations that include ‘omics’ methodology, which is usually not available in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

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Combined and sequential non-invasive approach to diagnosing non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease and persistently normal alanine aminotransferase levels

Zheng

Liu

Pan

et al. 2020

BMJ Open Diab Res Care

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Background and aimImaging-confirmed non-alcoholic fatty liver disease (NAFLD) with normal alanine aminotransferase (nALT) levels is infrequently the subject for further evaluation. Early diagnosis of non-alcoholic steatohepatitis (NASH) is needed to prevent disease progression. Thus, we tested the clinical utility of serum Golgi protein 73 (GP73) levels and developed a new non-invasive score to diagnose NASH in patients with biopsy-confirmed NAFLD and persistent nALT levels.MethodsSerum GP73 and cytokeratin-18 M30 fragments (CK18-M30) levels were measured in 345 patients with biopsy-proven NAFLD. We developed a new score, named G-NASH model (by incorporating serum GP73), and combined it with serum CK18-M30 measurement in a sequential non-invasive approach to accurately identify NASH among patients with NAFLD and persistent nALT levels.Results105 (30.4%) patients had persistent nALT, 53 of whom had histologically confirmed NASH. Both serum GP73 and CK18-M30 levels alone had poor diagnostic accuracy in identifying NASH (55.2% and 51.6%, respectively) in these patients. Conversely, G-NASH model performed better than other established non-invasive scoring systems, and by using our proposed sequential non-invasive approach 82.9% of patients with NASH were correctly identified.ConclusionsNASH is highly prevalent in patients with NAFLD with persistent nALT levels. The G-NASH model accurately identifies NASH in this patient group.

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Section: Discussioncontrasting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Combined and sequential non-invasive approach to diagnosing non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease and persistently normal alanine aminotransferase levels

Zheng

Liu

Pan

et al. 2020

BMJ Open Diab Res Care

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“…Studies have investigated the role of CK-18 in NAFLD patients; however, few studies have examined the serum CK-18 concentration in patients with T2DM. 14,15 Furthermore, in examining the extensive application of CK-18 for the study of NAFLD, it is not clear whether the CK-18 concentration is naturally affected by hyperglycaemia milieu. Moreover, it is important to establish the diagnostic value of CK-18 for the identification of NAFLD in T2DM patients in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Elevated serum cytokeratin-18 concentration in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease

Chang

Lin²,

Hwu

et al. 2018

Ann Clin Biochem

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Background Serum cytokeratin-18 is believed to be a marker of hepatic cell damage. However, few studies have discussed about the serum cytokeratin-18 concentration in type 2 diabetes mellitus patients and investigated its association with non-alcoholic fatty liver disease as well as metabolic biomarkers. Methods Healthy participants and type 2 diabetes mellitus patients were enrolled. Physical and metabolic factors were recorded, and non-alcoholic fatty liver disease was screened by abdominal ultrasound and the fatty liver index. The cytokeratin-18 concentration was detected using two commercially available immunoassay kits (M30 and M65 ELISA kit, Previa AB, Sweden). Results Overall, 22.8% (29/127) and 35.9% (42/117) of the participants were diagnosed with non-alcoholic fatty liver disease in the non-diabetes mellitus group and type 2 diabetes mellitus group, respectively. In the non-diabetes mellitus group and type 2 diabetes mellitus group, our result showed that participants with non-alcoholic fatty liver disease had a higher serum cytokeratin-18 M30 and cytokeratin-18 M65 concentration as compared with participants without non-alcoholic fatty liver disease. Interestingly, as compared with healthy participants without non-alcoholic fatty liver disease, our result also demonstrated that type 2 diabetes mellitus patients without non-alcoholic fatty liver disease had a higher serum cytokeratin-18 M30 (108.4 ± 66.2 vs. 87.1 ± 34.6 U/L; P = 0.038) and cytokeratin-18 M65 concentration (285.4 ± 115.3 vs. 248.5 ± 111.3 U/L; P = 0.031). The independent relationship between type 2 diabetes mellitus and cytokeratin-18 was further strengthened by the significant positive association between fasting plasma glucose and serum cytokeratin-18 concentration via multivariate regression analyses (cytokeratin-18 M30: β = 0.034, P = 0.029; cytokeratin-18 M65: β = 0.044, P = 0.002). Conclusions Independent of non-alcoholic fatty liver disease, our results suggested that the cytokeratin-18 concentration is closely associated with the hyperglycaemic milieu. The association between serum cytokeratin-18 and type 2 diabetes mellitus may be worthy of further investigation.

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“…[7] Previous efforts have been made to discover novel biomarkers or test panels to better distinguish NASH from simple steatosis. Some studies have suggested that measurement of serum CK18-M30 levels may be useful; [26,27] although one study has concluded that CK18-M30 measurement alone lacked sufficient sensitivity for diagnosing NASH. [28] Similarly, in the present study, we found that a substantial number of patients with persistently nALT (53 out of 105) had NASH on histology, and more importantly, serum CK18-M30 levels alone did not have sufficiently high diagnostic accuracy…”

Section: Discussionmentioning

confidence: 99%

“…ability to accurately identify NASH in patients with NAFLD and abnALT. [27,38] However, these non-invasive clinical scoring systems are complex combinations that include "omics" methodology, which is usually not available in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

A combined and sequential non-invasive approach to diagnosing non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease and persistently normal alanine aminotransferase levels

Zheng¹,

Liu²,

X³

et al. 2020

Journal of Hepatology

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The cytokeratin-18 fragment level as a biomarker of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus

Cited by 19 publications

References 38 publications

Combined and sequential non-invasive approach to diagnosing non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease and persistently normal alanine aminotransferase levels

Combined and sequential non-invasive approach to diagnosing non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease and persistently normal alanine aminotransferase levels

Elevated serum cytokeratin-18 concentration in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease

A combined and sequential non-invasive approach to diagnosing non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease and persistently normal alanine aminotransferase levels

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