Serum Levels of CK18 M30 and Leptin Are Useful Predictors of Steatohepatitis and Fibrosis in Paediatric NAFLD

Fitzpatrick, Emer; Mitry, Ragai R.; Quaglia, Alberto; Hussain, Munther J.; Bruyne, Ruth De; Dhawan, Anil

doi:10.1097/mpg.0b013e3181e376be

Cited by 94 publications

(79 citation statements)

References 27 publications

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“…However, HA was unable to differentiate between F1 and F2 fibrosis in a similar cohort (89). HA also did not achieve significance in predicting steatohepatitis or significant fibrosis in a small sample of 45 children with biopsy-proven NAFLD (90). Mean HA levels were close to the cut-off point for normal (≤50 ng/mL) in a small NAFLD sample (mean 47.1 ± 56.2 in males and 52.3 ± 47.8 in females).…”

Section: Hyaluronic Acid In Autoimmune Hepatitiscontrasting

confidence: 47%

Hyaluronic acid as a non-invasive biomarker of liver fibrosis

Neuman

Cohen

Nanau

2016

Clinical Biochemistry

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Section: Hyaluronic Acid In Autoimmune Hepatitiscontrasting

confidence: 47%

Hyaluronic acid as a non-invasive biomarker of liver fibrosis

Neuman

Cohen

Nanau

2016

Clinical Biochemistry

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“…A value of p<0.050 was considered statistically significant the other hand, leptin up-regulates the expression of CD11b on neutrophils, an early marker of activation which is also involved in neutrophil localization at inflammatory sites [41]. As leptin is augmented in pediatric patients with NAFLD [42], the positive correlation between the number of infiltrating PMN neutrophils and ROS generation might reveal a link between a greater activation status of peripheral neutrophils and the recruitment of these cells to the liver. Even though leptin also activates monocytes [43], the present functional study based on ROS generation failed to reveal a monocyte inflammatory phenotype in pediatric patients, in agreement with our previous results in adult NASH [23].…”

Section: Discussionmentioning

confidence: 99%

The Role of Innate Cells Is Coupled to a Th1-Polarized Immune Response in Pediatric Nonalcoholic Steatohepatitis

et al. 2012

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“…Liver enzymes were measured using standard automated kinetic enzymatic assays. CK18 was measured using immune-based (ELISA) assay as previously reported by Feldstein et al (14,16,17). Plasma-free fatty acids were assayed by a colorimetric method.…”

Section: Biochemical Analysismentioning

confidence: 99%

Circulating Levels of FGF-21 in Obese Youth: Associations With Liver Fat Content and Markers of Liver Damage

Giannini

Feldstein

Santoro

et al. 2013

The Journal of Clinical Endocrinology &Amp; Metabolism

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Objective: Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates glucose and lipid metabolism in rodents. The effects of obesity and fatty liver on circulating FGF-21 levels have been described mainly in adults. Herein, we measured plasma FGF-21 levels in lean and obese adolescents with low and high hepatic fat content (HFF% Ͻ5.5% and HFF% Ն5.5%, respectively) and explored their relationship with hepatic fat content, measures of hepatic apoptosis, and insulin sensitivity.Methods: A total of 217 lean and obese adolescents with both low and high HFF% (lean ϭ 31; obese low HFF% ϭ 107; and obese high HFF% ϭ 79) underwent an oral glucose tolerance test, a fast gradient magnetic resonance imaging to measure the %HFF and abdominal fat distribution. Cytokeratin 18 levels were measured as a biomarker of liver apoptosis. A subset of adolescents underwent a 2-step hyperinsulinemic-euglycemic clamp, and a liver biopsy (N ϭ 14), to assess insulin sensitivity and steatohepatitis, respectively. Results:Compared to controls, FGF-21 levels were higher in obese youth, especially in those with high HFF (P Ͻ .001). FGF-21 significantly correlated with adiposity indexes (P Ͻ .001), visceral fat (r 2 ϭ 0.240, P Ͻ .001), hepatic fat content (r 2 ϭ 0.278, P Ͻ .001), cytokeratin 18 (r 2 ϭ 0.217, P Ͻ .001), and alanine aminotransferase (r 2 ϭ .164, P Ͻ .001). In subjects with steatoheaptitis, FGF-21 levels significantly correlated with the nonalcoholic fatty liver disease activity score (r 2 ϭ 0.27, P ϭ .04).Stepwise regression analysis indicated that these relationships are independent of body mass index, visceral fat, and insulin sensitivity. An inverse correlation was documented with insulin, hepatic resistance indexes, and adipose resistance indexes, which disappeared after adjusting for hepatic fat content. Abbreviations: ALT, alanine aminotransferase; BMI, body mass index; BMI-Z, body mass index Z score; CK18, cytokeratin 18; FGF, fibroblast growth factor; HFF%, high hepatic fat content; MRI, magnetic resonance imaging; NAFLD, nonalcoholic fatty liver disease; NAS, nonalcoholic fatty liver disease activity; NASH, non-alcoholic steatohepatitis; WBISI, whole body insulin sensitivity index. Conclusions

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Serum Levels of CK18 M30 and Leptin Are Useful Predictors of Steatohepatitis and Fibrosis in Paediatric NAFLD

Abstract: The present study combines use of markers for different processes in the development of steatohepatitis. Serum biomarkers, especially CK18 M30, are useful in stratifying disease severity in paediatric NAFLD.

Cited by 94 publications

References 27 publications

Hyaluronic acid as a non-invasive biomarker of liver fibrosis

Hyaluronic acid as a non-invasive biomarker of liver fibrosis

The Role of Innate Cells Is Coupled to a Th1-Polarized Immune Response in Pediatric Nonalcoholic Steatohepatitis

Circulating Levels of FGF-21 in Obese Youth: Associations With Liver Fat Content and Markers of Liver Damage

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