Patologìâ (Dec 2020)
Diagnostic accuracy of apoptosis markers in non-alcoholic fatty liver disease in children
Abstract
Introduction. Non-alcoholic fatty liver disease (NAFLD) is recognized as one of the most common chronic liver diseases in children and adults worldwide. Early diagnosis of rapidly progressive forms of NAFLD – non-alcoholic steatohepatitis (NASH) – is crucial, because therapeutic intervention in the early disease stages creates unique opportunities for the reversal of pathological changes and restoration of liver structure and function. Despite the variety of currently available diagnostic scales and indices, laboratory diagnosis of NAFLD in children requires new non-invasive tests and their validation. Aim: To investigate the differences of cytokeratin-18 (CK18) and the combined marker MACK-3 levels in children with nonalcoholic steatohepatitis (NASH), simple hepatic steatosis, overweight and obese children without hepatic steatosis. Materials and methods. The study included 170 patients aged 6 to 17 years. The mean age of patients was (12.15 ± 2.51) years. According to the presence of steatosis, steatohepatitis, overweight and obesity, patients were divided into 4 groups: the 1st group consisted of 37 patients with NASH, the 2nd group – 53 patients with simple steatosis, the 3rd group – 65 overweight and obese patients without hepatic steatosis, the 4th group (control) – 15 patients with normal weight without steatosis. Biochemical hepatogram, carbohydrate metabolism investigation, as well as CK18 enzyme-linked immunosorbent assay, were conducted with the MACK-3 calculation. Results. The average level of CK18 in children with NASH increased by 1.6 times (P <0.05) compared with children of the control group. The median CK18 level in patients with NASH was by 1.6 times (P < 0.05) and 2.0 times (P < 0.05) higher than in groups 2 and 3, respectively. T he threshold level of CK18 for the diagnosis of NASH was 87.4 U/l: its sensitivity was 81.8 %, specificity 70 %, AUROC 0.736 (P ˂ 0.05). Calculated index MACK-3 revealed a significant increase in children with NASH compared with other groups (P < 0,05). Threshold level of MACK-3 for the diagnosis of NASH was 0.053: sensitivity – 90.9 %, specificity – 81.6 %, AUROC 0.958 (P ˂ 0.05). Conclusions. Thus, in children with NASH, a significant increase in the CK18 level was found, which can be used for early non-invasive diagnosis of NASH in children. The advantage of the calculated index MACK-3 is the increase in diagnostic accuracy and the possibility of its use to stratify the risk of the progressive course of NAFLD, which will streamline the selection of patients for active therapeutic intervention.
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