Metabolic Syndrome Is Associated With Advanced Liver Fibrosis Among Pediatric Patients With Non-alcoholic Fatty Liver Disease

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) among children is a growing concern with potential significant outcome. This study aims to investigate the relationship between hepatic steatosis, metabolic syndrome, and liver fibrosis among children with obesity and diabetes mellitus.Methodology: Children aged 6–18 years old were recruited from pediatric obesity and diabetes clinic in University Malaya Medical Center (UMMC) between year 2016 and 2019. Data on basic demographics, anthropometric measurements and clinical components of metabolic syndrome were collected. Transient elastography was performed with hepatic steatosis and liver fibrosis assessed by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) respectively. Mild, moderate and severe steatosis were defined as >248, >268, and >280 dB/m respectively, and LSM above 7.0 kPa for fibrosis stage F ≥ 2, 8.7 kPa for F ≥ 3, and 10.3 kPa for F4 (cirrhosis).Results: A total of 57 children (60% male) with median age of 13 years old were recruited. Fifty (87.7%) of the children are obese and 27 (54%) out of 50 are morbidly obese. Among 44 (77.2%) patients with steatosis, 40 (70.2%) had severe steatosis and 18 (40.9%) had developed liver fibrosis of stage 2 and above. Advanced fibrosis or cirrhosis was detected in 8 (18.2%) children with presence of steatosis. Twenty-three out of 57 (40.4%) was diagnosed with metabolic syndrome. Fibrosis is three times more likely to occur in the presence of metabolic syndrome (OR = 3.545, 95% CI: 1.135–11.075, p = 0.026). Waist circumference is a significant predictor of fibrosis after multiple regression analysis.Conclusion: Obese children with metabolic syndrome are more likely to have advanced liver fibrosis compared to those without metabolic syndrome. Waist circumference predicts development of liver fibrosis.

Normal liver stiffness and influencing factors in healthy children: An individual participant data meta‐analysis

“…The same observation has been demonstrated in the adult population 3 . Importantly, this trend towards increased LSM in patients with diabetes may suggest early underlying and undetected fibrosis, as the metabolic syndrome has been associated with advanced liver fibrosis among paediatric NAFLD patients 39 . Our finding warrants further evaluation in larger cohorts.…”

“…The same observation has been demonstrated in the adult population 3. Importantly, this trend towards increased LSM in patients with diabetes may suggest early underlying and undetected fibrosis, as the metabolic syndrome has been associated with advanced liver fibrosis among paediatric NAFLD patients 39. Our finding warrants further evaluation in larger cohorts.The impact of hepatic inflammation (as determined by an elevated ALT) on LSM is well described in the adult population40 and has recently become appreciated in the paediatric population, particularly in patients with minimal or no fibrosis at baseline 41.…”

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

“…Fujii et al showed that HOMA-IR and age are independent predictors of advanced fibrosis in patients with NAFLD but without T2DM [ 63 ]. In contrast, a cross-sectional study in children with obesity and diabetes mellitus showed that HOMA-IR is not an independent predictor of liver fibrosis assessed by LSM [ 64 ].…”

From Nonalcoholic Fatty Liver Disease (NAFLD) to Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)—New Terminology in Pediatric Patients as a Step in Good Scientific Direction?

“…Moreover, metabolic components such as BMI, WC, systolic blood pressure (SBP), serum triglycerides (TG) levels, serum total cholesterol (TC) level, hemoglobin A1c (HbA1c), 2TDM, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly higher in patients with liver fibrosis. Multivariate regression analysis shown that waist circumference is a significant independent predictor of liver fibrosis [ 46 ]. Analyses of one of the studies, which was conducted in a large cohort of obese adolescents (1278 participants), from 25 German, Austrian, and Swiss centers specializing in pediatric obesity, revealed that elevated waist circumference, as well as BMI, are strongly correlated to parameters of hepatocyte injury—ALT and gammaglutamyl transferase (GGT) [ 31 ].…”