Cytokine-dependent mechanisms of the immune response implementation in patients with non-alcoholic fatty liver disease and arterial hypertension

Abstract

The relevance of studying clinical and laboratory manifestations and liver inflammatory activity in patients with non‑alcoholic fatty liver disease (NAFLD) and arterial hypertension (HTN) is high, as it determines the aspects of preliminary diagnosis in patients from risk groups and allows to adjust of the diagnostic and therapeutic tactics of managing these patients. Objective — to study the ways of cytokine‑determined immune reactions implementation in patients with NAFLD and concomitant HTN. Materials and methods. The study involved 120 patients with NAFLD, from them 49 patients (67.3 % women and 32.7 % men) had concomitant HTN (the main group); 51 patients (58.5 % women and 41.2 % men) had isolated NAFLD (comparison group). The control group consisted of 20 relatively healthy subjects (55.0 % women and 45.0 % men). Body mass index (BMI) was calculated, and several biochemical indices were evaluated. The standard kinetic method was used to define levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The enzymatic colorimetric method was used to measure γ‑glutamylpeptidase levels, and levels of alkaline phosphatase, total protein and albumin were measured with colorimetric method. The de Ritis index was calculated. The interleukins 8 and 10 levels were determined using the immunofluorescence method with ElabScience (USA) reagents. Ultrasound examination of the liver was performed according to the standard method on an empty stomach using the device Samsung (Medison) SonoAce X8 (South Korea). To compare the data in the study groups, the liver oblique‑vertical dimension (CVD) was used. Results. The BMI increase was determined in both groups: with NAFLD and concomitant HTN and with isolated course (respectively 27.8 [26.6; 28.5] and 27.3 [24.2; 28.3] kg/ m2) compared to the control group (24.3 [21.9; 26.0] kg/ m2, p < 0.001 and р = 0.004). The presence of concomitant HTN in patients with NAFLD was associated with the significant (p < 0.001) deviations in the functional liver state, which was manifested by the prevalence of ALT levels (45 [43.0; 47.5] U/ L), AST levels (53 [51.0; 56.0] U/ L), alkaline phosphatase levels (285.7 [217.6; 321.1] U/ L) and gamma‑glutamine transpeptidase levels (96.2 [75.0; 108.9] U/ L) in comparison with the isolated NAFLD levels (respectively 36 [34.0; 39.0] U/ L, 41 [40.0; 45.0] U/ L, 215.5 [183.2; 246.7] U/ L and 65.5 [51.5; 76.8] U/ L) and control group levels (respectively 25.5 [24.0; 30.8] U/ L, 23 [19.3; 26.0] U/ L, 129.2 [116.9; 140.6] U/ L and 22.6 [16.1; 31.7] U/ L). A significantly (p < 0.001) higher de Ritis index was determined in the main (1.16 [1.11; 1.24]) and comparison groups (1.14 [1.08; 1.21]) as compared to the control group (0.87 [0.76; 0.99]). Such changes in the liver functional activity correlated with the changes in cytokine‑determined immune reactions, which were manifested by a significant (p < 0.001) predominance of interleukin‑8 and interleukin‑10 levels in patients with NAFLD and HTN (respectively, 29.4 [25.6; 34.9] and 20.3 [17.1; 24.4] pg/ mL) and isolated NAFLD (22.5 [19.1; 25.8] and 12.1 [10.5; 13.7] pg/ mL) compared to the control group (7.4 [6.7; 8.9] and 3.6 [2.8; 5.0] pg/ mL). Conclusions. The course of NAFLD is associated with the development of cytokine imbalance. A systematic increase in blood pressure can lead to an increase of cytokine‑mediated immune reactions activity in patients with NAFLD and concomitant HTN.