The Search for Noninvasive Methods to Identify Liver Fibrosis in Children With Nonalcoholic Fatty Liver Disease

Mandelia, Chetan; Kabbany, Mohammad Nasser; Selvakumar, Praveen Kumar Conjeevaram; Alkhouri, Naim

doi:10.2217/bmm-2017-0038

Cited by 16 publications

(22 citation statements)

References 63 publications

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“…Therefore, noninvasive methods for diagnosis of liver fibrosis in children with NAFLD can be a safe and cost-effective alternatives to liver biopsy. Liver fibrosis in children can be detected by a combination of clinical and laboratory parameters, advanced biochemical markers or imaging techniques summarized in several review articles [42]. In clinical practice, a “pediatric NAFLD fibrosis index” (PNFI), developed by Nobili et al .…”

Section: Diagnosismentioning

confidence: 99%

Update on pathogenesis, diagnostics and therapy of nonalcoholic fatty liver disease in children

Flisiak-Jackiewicz¹,

Lebensztejn²

2019

ceh

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Nonalcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disease. Increasing prevalence of NAFLD in children may be the cause of unfavorable metabolic implications and development of end stage liver disease. NAFLD is a “multiple-hit” disease mediated by several metabolic, environmental, genetic and microbiological mechanisms. Additionally, lipotoxicity, oxidative stress and inflammation predispose to progressive liver damage. According to current guidelines, liver biopsy is an imperfect gold standard for NAFLD diagnosis, but due to its invasive character its use is limited in children and it should be performed only in children who need exclusion of coexisting diseases. Noninvasive methods should be preferred and current research is focused on serum markers and novel imaging or elastographic techniques. Therapeutic approaches for NAFLD are currently focused on lifestyle modification, insulin resistance, dyslipidemia, oxidative stress and the gut microbiome. However, a number of clinical studies on novel therapeutic molecules are ongoing.

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Section: Diagnosismentioning

confidence: 99%

Update on pathogenesis, diagnostics and therapy of nonalcoholic fatty liver disease in children

Flisiak-Jackiewicz¹,

Lebensztejn²

2019

ceh

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“…Despite several biomarkers have been linked to the presence of NAFLD, there has also a growing interest regarding newly proposed noninvasive markers 1,23,24…”

Section: New Biomarkersmentioning

confidence: 99%

“…Several alternative noninvasive methods for diagnosis of liver fibrosis in NAFLD pediatric patients have been proposed 24. Despite various fibrosis scores available in adults (e.g., AST/ALT ratio, AST to platelet ratio index, NAFLD fibrosis score, and fibrosis-4 index), valid alternatives to liver biopsy are still limited 1,23.…”

Section: Novel Noninvasive Techniques For Nafld Assessmentmentioning

confidence: 99%

<p>Pediatric non-alcoholic fatty liver disease: current perspectives on diagnosis and management</p>

Sessa¹,

Cirillo²,

Guarino³

et al. 2019

PHMT

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Non-alcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disease in childhood. To date, the “multiple-hit” hypothesis is largely recognized as an explanation of NAFLD pathogenesis and progression. Obesity and features of the metabolic syndrome have been closely linked to NAFLD development. Due to the increased prevalence of obesity worldwide, NAFLD has reached epidemic proportions over time. Given its unfavorable cardiometabolic burden (such as cardiovascular and metabolic consequences), it represents a worrying phenomenon needing a more comprehensive and successful management. Laboratory tests and classical imaging techniques play a pivotal role in NAFLD diagnosis, but novel noninvasive alternative methods to diagnose and monitor NAFLD have been investigated. Currently, lifestyle modifications remain the mainstay treatment, although its efficacy is poor because of the lack of compliance. Pediatric research is focusing on multiple alternative treatments targeting the main pathogenic factors such as insulin-resistance, dyslipidemia, gut-liver axis and microbiota, oxidative stress, and proinflammatory pathways. Results from these studies are promising but larger validation is needed. Innovative therapeutic approaches might add an important piece in the complex knowledge of pediatric NAFLD. We aimed to summarize recent insights into NAFLD diagnosis and treatment in children, with a focus on possible future perspectives in pediatric research.

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“…During apoptosis, activation of caspases occurs, which leads to proteolysis of cellular proteins including CK-18. This process can further cause the activation of stellate cells associated with fibrosis processes [4]. Therefore, the content of fragments of caspase-cleaved cytokeratin-18 in the serum, according to many researchers, may be one of the informative indicators of inflammation and fibrosis in NAFLD.…”

Section: Introductionmentioning

confidence: 99%

Cytokeratin-18 as a Marker of Non-Alcoholic Fatty Liver Disease in Obese Adolescents

Khomenko

2020

EUREKA: Health Sciences

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In parallel with the obesity epidemic in the world, the prevalence of non-alcoholic fatty liver disease among children and adolescents is growing. Current data suggest that insulin resistance is one of the main factors in the pathogenesis of non-alcoholic fatty liver disease, and the content of fragments of caspase-cleaved cytokeratin-18 in the blood serum may be one of the informative indicators of non-alcoholic fatty liver disease progression. The aim. To determine mechanisms of formation and progression of non-alcoholic fatty liver disease in obese children and adolescents by evaluating the level of cytokeratin-18. Materials and methods. The study involved 46 adolescents with obesity and non-alcoholic fatty liver disease aged 12–17 years: 19 boys (41.3 %) and 27 girls (58.7 %). Clinical (weight, height, waist and hip circumference), laboratory (glucose, immunoreactive insulin, lipid metabolism, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, cytokeratin-18) parameters were studied and instrumental examination (abdominal ultrasound) was performed. To assess insulin resistance the triglyceride-glucose index was calculated. Results. Depending on the presence of insulin resistance patients were divided into two groups: 21 (45.7 %) of adolescents with insulin resistance and 25 (54.3 %) of adolescents without insulin resistance. Blood tests in patients with insulin resistance revealed significantly higher levels of total cholesterol, triglycerides, very low-density lipoprotein cholesterol, fasting immunoreactive insulin, cytokeratin-18 and gamma-glutamyl transpeptidase. All adolescents were divided into 2 groups depending on the level of cytokeratin-18: patients with cytokeratin-18 >233 mIU/ml and <233 mIU/ml (15 (32.6 %) and 31 (67.4 %) respectively). It was found that there were significantly more patients with insulin resistance in the group with the level of cytokeratin-18 >233 mIU/ml. Conclusion. In obese adolescents with non-alcoholic fatty liver disease insulin resistance is associated with more pronounced disorders of lipid and carbohydrate metabolism and higher levels of markers that characterize the state of the liver such as cytokeratin-18 and gamma-glutamyl transpeptidase. Adolescents with obesity and non-alcoholic fatty liver disease with a threshold level of cytokeratin-18, which indicates the transformation of steatosis into steatohepatitis, two times more often have present insulin resistance.

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The Search for Noninvasive Methods to Identify Liver Fibrosis in Children With Nonalcoholic Fatty Liver Disease

Cited by 16 publications

References 63 publications

Update on pathogenesis, diagnostics and therapy of nonalcoholic fatty liver disease in children

Update on pathogenesis, diagnostics and therapy of nonalcoholic fatty liver disease in children

<p>Pediatric non-alcoholic fatty liver disease: current perspectives on diagnosis and management</p>

Cytokeratin-18 as a Marker of Non-Alcoholic Fatty Liver Disease in Obese Adolescents

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