Stratification by Non-invasive Biomarkers of Non-alcoholic Fatty Liver Disease in Children

Abstract

BackgroundThe spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from isolated hepatic steatosis to non-alcoholic steatohepatitis to fibrosis. We aimed to introduce useful biomarkers released during liver inflammation and fibrogenesis that are easy to use in outpatient clinic and adjust to children to evaluate each NAFLD stage without biopsy.MethodsThis prospective study included 60 patients aged under 19 years whose alanine aminotransferase (ALT) levels were elevated from March 2021. All patients were proven to have NAFLD by ultrasonography and laboratory work-up to exclude other causes of hepatitis. Fibroscan and additional laboratory tests for biomarkers [procollagen type1 amino-terminal propeptide (P1NP), osteocalcin, interleukin-6 (IL-6), and Mac-2 binding protein glycosylated isomer (M2BPGi)] were performed. Fibroscan-AST (FAST) score was used for the comparison of steatohepatitis and liver stiffness measurement (kPa) was used for the comparison of advanced fibrosis.ResultsThe biomarker that showed a significant difference between the FAST-positive and negative groups was the P1NP/osteocalcin ratio with a p-value of 0.008. The area under receiver operating characteristic (AUROC) of P1NP/osteocalcin ratio*ALT values (values obtained through multivariate analysis) was 0.939 with the cut-off value of 305.38. The biomarkers that showed a significant difference between the LSM-positive and negative groups were IL-6 and M2BPGi with a p-values of 0.005 and <0.001. AUROC of IL-6 *AST values (values obtained through multivariate analysis) was 0.821 with the cut-off value of 228.15. M2BPGi showed a significant linear relationship with LSM in Pearson correlation analysis (Pearson correlation coefficient = 0.382; p = 0.003). The diagnostic capability of M2BPGi to evaluate advanced fibrosis showed an acceptable result (AUROC = 0.742; p = 0.022).ConclusionsNon-invasive biomarkers can be used to predict each stage of NAFLD in children. The measurements of P1NP, IL-6 or M2BPGi along with the basic chemistry tests would help determine the stage of NAFLD they correspond to at the time of initial diagnosis and predict responsiveness after the treatment.

Diagnostic Performance of Biomarker-Based Scores as Predictors of Metabolic Dysfunction-Associated Fatty Liver Disease Risk in Healthy Children

“…Non-invasive assessment of liver fibrosis relies on imaging techniques and/or different algorithms including biochemical markers of fibrosis and/or linked to fibrogenesis [ 8 ]. The features of NAFLD in children are different in comparison to adults with more likely steatosis and steatohepatitis; however, the elastography-based techniques have proven to be suitable also in the pediatric population for determination the stage of fibrosis [ 7 , 9 , 10 ]. Measurement of liver stiffness with transient elastography is suggested as a promising procedure for screening and monitoring fibrosis in pediatric NAFLD [ 6 ].…”

“…Several non-invasive methods based on the assessment of biochemical markers were proposed for the diagnosis of NAFLD with a particular focus on the detection of early fibrosis [ 9 , 10 ]. The combination of blood biomarkers with clinical features may improve the sensitivity of the scoring systems; however, their predictive value depends on the characteristics of studied population [ 11 ].…”

“…Recently, serum biomarkers of inflammation (IL-6) and extracellular matrix components ( N -terminal propeptide of type I procollagen (P1NP), Mac-2 binding protein glycosylation isomer (M2BPGi), type III procollagen (PIIINP) and hyaluronic acid) generated during fibrogenesis, were indicated as useful for determination the stages of NAFLD in children and adolescents [ 9 , 12 ]. Both PIIINP and hyaluronic acid were assessed as new promising biomarkers in obese children with NAFLD [ 12 ].…”

“…Both PIIINP and hyaluronic acid were assessed as new promising biomarkers in obese children with NAFLD [ 12 ]. P1NP/osteocalcin ratio or P1NP/alkaline phosphatase ratio along with alanine aminotransferase showed good diagnostic ability in predicting early fibrosis in children and adolescents with ultrasonography-proven NAFLD [ 9 ].…”

Pediatric percentiles for transient elastography measurements - effects of age, sex, weight status and pubertal stage

“…Various serum parameters and imaging procedures have been evaluated in several studies over the last years, but mostly with rather disappointing results ( 2 , 6 , 8 – 10 ). Measurement of alanine transaminase (ALT), for instance, is the most common serum parameter for screening, but physiological levels are no reliable predictor for the absence of NAFLD.…”