Determination of fibrosis predictors in patients with non-alcoholic fatty liver disease

Abstract

Objective — to determine the prognostic role of markers of systemic inflammation and signaling molecules in the development of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).
 Materials and methods. Examinations involved 84 patients with NAFLD in combination with components of the metabolic syndrome. Metabolic parameters were studied using standard methods. Markers of systemic inflammation (CRP and TNF‑α, cytokeratin‑18 (CK‑18)) and miRNA‑34a and miRNA‑122 were determined. The ultrasound method was used to diagnose liver fibrosis. Mathematical statistics methods were used to evaluate associations of indicators.
 Results. Significantly higher expression levels of miRNA‑34a were determined in patients with morbid obesity compared to NAFLD patients with excessive body mass and first and second degree obesity. The analysis of the dependence of serum markers of inflammation on the activity of visceral adipose tissue (VAT) showed the increase in TNF‑α and CRP levels along with the increase of its activity. Moreover, the CK‑18 levels in patients with NAFLD varied depending on the VAT activity, which indicates the influence of this marker on the development and progression of metabolic disorders in polymorbid patients. When comparing the expression level of miRNA‑34a with different activity of visceral adipose tissue, the maximum values of the studied indicator were found in the group of patients with high index of visceral obesity (IVO). The obtained may indicate possible effects of miRNA‑34a on the activation of lipogenesis and disruption of the distribution of adipose tissue in the direction of an increase in its visceral component. The revealed relationships between miRNA‑122 and insulin resistance, disorders of lipid metabolism, markers of cytolytic damage of hepatocytes and pro‑inflammatory cytokines indicate the triggering role of miRNA‑122 in the progression of NAFLD (p < 0.05). In patients with steatosis of the 3rd degree, significant differences in the level of relative normalized expression of miRNA‑34a were observed compared to the indicators of the group of steatosis of the 1st degree. In fibrosis of high grades (F3 — F 4), significantly higher expression of miRNA‑122 was observed. At the initial stages of fibrosis (F1—F2) a moderate increase in the levels of the studied miRNA was also observed.
 Conclusions. Determining the expression level of miRNA‑122 can be a potential non‑invasive predictor of fibrosis progression in NAFLD patients.