Robust Detection of Liver Steatosis and Staging of NAFLD by an Improved ELISA for Serum Cytokeratin-18 Fragments

The goal. To determine the value of the triglyceride glucose index (TGI) for the diagnosis of insulin resistance (IR) in early forms of non-alcoholic fatty liver disease (NAFLD).Materials and methods. 99 patients with NAFLD were examined: 38 (38.4%) with liver steatosis (LS) and 61 (61.6%) with steatohepatitis (SH). TGI was determined by the formula — In [fasting TG (mg / dl) × fasting glucose (mg / dl) / 2], patients with LS and SH were divided into quartiles (Q1-Q4) by increasing TGI levels with an assessment of liver tests, insulin levels (“Insulin TEST System”, Monobind Inc., USA), HOMA-IR, fragments of cytokeratin-18 (FCK-18) ("TPS ELISA, Biotech”, Sweden) and TNF-α (“Human TNFα Platinum” ELISA, eBioscience, Austria).Results. In patients with LS with a TGI increase from Q1 to Q4, HOMA-IR increased from 1.12 ± 0.48 to 6.02 ± 3.15 (p <0.05), a direct relationship was found between these indicators — r = 0.52 (p = 0.03). TGI also correlated with waist circumference — r = 0.81 (p = 0.01), cholesterol — r = 0.51 (p = 0.002), alkaline phosphatase — r = 0.41 (p = 0.02). In patients with SH, from Q1 to Q4, HOMA-IR increased from 3.15 ± 1.8 to 6.2 ± 3.04 (p <0.05), but there was no significant correlation between HOMA-IR and TGI. The levels of FCK-18 increased from Q1 to Q4-139.82 ± 72.45 to 359.75 ± 189.03 U / L (p <0.05) and TNF-α — from 6.38 ± 1.25 pg / ml up to 7.75 ± 1.09 pg / ml (p <0.05). There was a connection between TGI and the level of a marker of hepatocyte apoptosis — FCK-18 — r = 0.43 (p = 0.004).Conclusion. In liver steatosis, TGI has demonstrated its diagnostic role as a surrogate marker of insulin resistance, correlating with HOMA-IR. In steatohepatitis, TGI reflected the degree of hepatocytic apoptosis, correlating with fragments of cytokeratin-18.

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Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis

Nutrients ◽

10.3390/nu12020476 ◽

2020 ◽

Vol 12 (2) ◽

pp. 476

Author(s):

Joanna Góralska ◽

Urszula Raźny ◽

Anna Polus ◽

Agnieszka Dziewońska ◽

Anna Gruca ◽

...

Keyword(s):

Odds Ratio ◽

Liver Steatosis ◽

Potential Contribution ◽

Fibroblast Growth ◽

Epigenetic Factors ◽

Cytokeratin 18 ◽

Biochemical Alteration ◽

Fatty Liver Index ◽

Fatty Acids Metabolism ◽

Expression Pathways

Nutrient excess enhances glucose-dependent insulinotropic polypeptide (GIP) secretion, which may in turn contribute to the development of liver steatosis. We hypothesized that elevated GIP levels in obesity may affect markers of liver injury through microRNAs. The study involved 128 subjects (body mass index (BMI) 25–40). Fasting and postprandial GIP, glucose, insulin, and lipids, as well as fasting alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), cytokeratin-18, fibroblast growth factor (FGF)-19, and FGF-21 were determined. TaqMan low density array was used for quantitative analysis of blood microRNAs. Fasting GIP was associated with ALT [β = 0.16 (confidence interval (CI): 0.01–0.32)], triglycerides [β = 0.21 (95% CI: 0.06–0.36], and FGF-21 [β = 0.20 (95%CI: 0.03–0.37)]; and postprandial GIP with GGT [β = 0.17 (95%CI: 0.03–0.32)]. The odds ratio for elevated fatty liver index (>73%) was 2.42 (95%CI: 1.02–5.72) for high GIP versus low GIP patients. The miRNAs profile related to a high GIP plasma level included upregulated miR-136-5p, miR-320a, miR-483-5p, miR-520d-5p, miR-520b, miR-30e-3p, and miR-571. Analysis of the interactions of these microRNAs with gene expression pathways suggests their potential contribution to the regulation of the activity of genes associated with insulin resistance, fatty acids metabolism, and adipocytokines signaling. Exaggerated fasting and postprandial secretion of GIP in obesity are associated with elevated liver damage markers as well as FGF-21 plasma levels. Differentially expressed microRNAs suggest additional, epigenetic factors contributing to the gut–liver cross-talk.

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Relationship between Serum Cytokeratin-18, Control Attenuation Parameter, NAFLD Fibrosis Score, and Liver Steatosis in Nonalcoholic Fatty Liver Disease

International Journal of Hepatology ◽

10.1155/2018/9252536 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Sumitro Kosasih ◽

Wong Zhi Qin ◽

Rafiz Abdul Rani ◽

Nazefah Abd Hamid ◽

Ngiu Chai Soon ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Liver Steatosis ◽

Fibrosis Score ◽

Cytokeratin 18 ◽

Nonalcoholic Fatty Liver ◽

Attenuation Parameter ◽

Nafld Fibrosis Score

Backgrounds. The aim of this study was to appraise the relationship between serum fragmented cytokeratin-18(CK-18), controlled attenuation parameter (CAP), and liver steatosis assessed by ultrasound (US) in nonalcoholic fatty liver disease (NAFLD) patients. Methods. Patients who underwent abdominal US were recruited, followed with measurement of CAP using Fibroscan® and serum fragmented CK-18 using enzyme-linked immunosorbent assay. The degree of liver steatosis assessed by US was categorized into mild (S1), moderate (S2), and severe (S3). Results. A total of 109 patients were included in our study. CAP and fragmented CK-18 level were significantly correlated with liver steatosis grade with rs = 0.56 and 0.68, p=0.001, respectively. NAFLD Fibrosis Score was poorly correlated with liver steatosis grade (rs=-0.096, p=0.318). Using fragmented CK-18 level, area under receiver operating characteristic (AUROC) curves for S≥2 and S≥3 were excellent (0.82 and 0.84, respectively). Using CAP, AUROC curves for detection of S≥2 and S≥3 were good (0.76, 0.77, respectively). We also proposed cut-off value of CAP to detect S≥2 and S≥3 to be 263 and 319db/m, respectively, and fragmented CK-18 level to detect S≥2 and S≥3 (194 and 294 U/L, respectively). Conclusions. Both the fragmented CK-18 level and the CAP, but not NAFLD Fibrosis Score, were well correlated with hepatic steatosis grade as assessed by US.

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The use of cytokeratin-18 fragments in diagnostics of non-alcohol fatty liver disease

Clinical Medicine (Russian Journal) ◽

10.18821/0023-2149-2017-95-10-923-927 ◽

2017 ◽

Vol 95 (10) ◽

pp. 923-927

Author(s):

A. A. Shipovskaya ◽

I. V. Kurbatova ◽

Olga P. Dudanova

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Activity Index ◽

Liver Steatosis ◽

Differential Diagnostics ◽

Tnf Alpha ◽

Control Group ◽

Activity Measurement ◽

Cytokeratin 18

Aim. To evaluate the value of cytokeratin-18 fragments (CKF-18) for diagnostics of non-alcohol fatty liver disease (NAFLD): liver steatosis (LS) and steatohepatitis (SH). Material and methods. We examined 148 patients with NAFLD (94 men, 49 women) including 28 (19.6%) with LS and 115 (80.4%) with SH (mean age 48.85±10.36 and 48.6±12.0 years respectively). The diagnosis was verified based on clinical, ultrasonic, and liver biopsy (in 17 (12.0%) patients) data. CKF-18 were measured by the immunoenzyme assay (TPS ELISA,Biotech, Sweden) and TNF-alpha with the use of a Human TNFα Platinum ELISA kit (Bioscience, Austria). Control group consisted of 27 healthy donors. Results. CKF-18 level in SG patients (420.5±426.9 U/l) was significantly higher than in LS patients and healthy subjects (126.13±48.0 and 129.27±59.78 U/l respectively). TNF-alpha levels were 6.28±0.5, 5.15±0.6, and 4.81±0.7 pg/ml respectively (p<0,05). Correlation of CKF-18 levels with the following parameters was documented : ALT (r=+0,45, p<0,05); AST (r=+0,43, p<0,05), triglycerides (r=+0,25, p<0,05), HDLP (r=-0,21, p<0,05), histological activity index (r=+0,46, p<0,05). No correlation was found between CKF-18 and TNF-alpha levels or between CKF-18 and severity of fibrosis. Conclusion. CKF-18 levels in SH patients are significantly higher than in LF patients and correlate with histological signs of SH activity. Measurement of TNF-alpha can be used for differential diagnostics of SH and LF. Significant elevation of aminotransferase activities and CKF-18 levels in SH compared with LF and their close correlation confirms the important role of necrosis and hepatocyte apoptosis in pathogenesis of NAFLD.

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Therapeutic Effect of Metformin and Vitamin E Versus Prescriptive Diet in Obese Adolescents with Fatty Liver

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000086 ◽

2011 ◽

Vol 81 (6) ◽

pp. 398-406 ◽

Cited By ~ 17

Author(s):

Akcam ◽

Boyaci ◽

Pirgon ◽

Kaya ◽

Uysal ◽

...

Keyword(s):

Insulin Resistance ◽

Vitamin E ◽

Fatty Liver ◽

Liver Steatosis ◽

Tnf Alpha ◽

Dietary Advice ◽

Model Assessment ◽

Fasting Insulin ◽

Alcoholic Fatty Liver ◽

Obese Adolescents

Objective: The aim of the study was to determine whether metformin or vitamin E treatment for six months is effective in reducing body weight, blood pressure, and also ameliorating insulin resistance, adiponectin, and tumor necrosis factor (TNF)-alpha in obese adolescents with non-alcoholic fatty liver disease (NAFLD). Methods: Sixty-seven obese adolescents with liver steatosis (age range, 9 - 17 years) were included in the study. The metformin group received an 850-mg dose of metformin daily and the vitamin E group received 400 U vitamin E /daily, in capsule form for 6 months, plus an individually tailored diet, exercise, and behavioral therapy. Results: After 6 months later, there was a significant decline in body mass index, and fasting insulin and homeostatic model assessment (HOMA) values in all three groups. Moreover, in comparingson of changes in HOMA among the groups, the metformin- treated group showed significantly improved metabolic control and insulin sensitivity (HOMA) at the end of the study. There were no significant differences for changes of adiponectin, TNF-alpha, in all three groups after 6 months study. Conclusion: These data suggest that metformin treatment is more effective than dietary advice and vitamin E treatment in reducing insulin resistance, and also in ameliorating metabolic parameters such as fasting insulin and lipid levels, in obese adolescents having NAFLD.

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