Cytokine imbalance and progression of changes in the liver parenchyma in patients with non-alcoholic fatty liver disease and essential hypertension

Abstract

Objective — to determine the relationship between the activity of pro‑ and anti‑inflammatory cytokines and liver functional parameters in patients with non‑alcoholic fatty liver disease (NAFLD) and hypertension (HTN), depending on the degree of liver parenchyma damage. Materials and methods. The study included 120 people, divided into 3 groups: 49 patients (67.3% women) with NAFLD and concomitant HTN (main group); 51 patients (58.5% women) with isolated NAFLD (comparison group) and 20 relatively healthy individuals (55.0% women and 45.0% men) of the control group. In the main group, 55.1% of patients had steatosis, 44.9% had steatohepatitis. In the comparison group, 58.8% had steatosis, 41.2% had steatohepatitis (χ2=0.141, p=0.707). The assessments included body mass index (BMI), levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), γ‑glutamine transpeptidase, interleukin 8 and 10 (IL‑8, IL‑10), alkaline phosphatase (ALP), De Ritis index (AST/ALT ratio). The diagnosis of NAFLD and HTN was established in accordance with the local and international recommendations. Ultrasound examination of the liver was performed according to the standard method in fasting condition. Results. Body mass index corresponded to the normal or increased body weight: in the main group — 27.8 [26.6; 28.5] kg/m2 and 27.3 [24.2; 28.3] kg/m2 in the comparison group, in the control group — 24.3 [21.9; 26.0] kg/m2 (p<0.001 and p=0.004 respectively). The results of the biochemical analysis showed a significant (p<0.001) predominance of AST and ALT in patients with steatohepatitis compared to patients with steatosis, both in the main/group (AST=56.5 [54.0, 57.0] U/l and ALT=47.0 [44.5; 49.0] U/L, respectively), and in the comparison group (AST=45.0 [43.0; 48.0] U/l and ALT 39.0 [35.0; 42.0] U/L, respectively). The analysis of correlational relationships in patients with steatohepatitis, stronger relationships were found, both between the systemic increase in blood pressure, and between the cytokine’s levels and liver functional parameters. Thus, in patients of the main group with steatohepatitis, an inverse relationship was determined between the levels of AST and anti‑inflammatory IL‑10 (r=–0.588, p=0.004), the levels of GGTP (r=–0.407 p=0.060) and the levels of albumin (r=– 0.466, p=0.069). In patients of the comparison group and steatohepatitis, an inverse correlation was determined between the levels of diastolic blood pressure and GGTP (r=0.490, p=0.024). GGTP levels were also inversely correlated with AST levels (r=–0.508, p=0.019) and directly with IL‑8 and IL‑10 levels (r=0.438, p=0.049 and r=0.373, p=0.096). IL 10 demonstrated a strong negative correlation with albumin levels (r=–0.604, p=0.004). IL‑8 levels showed a direct correlation with IL‑10 (r=0.431, p=0.051) in this subgroup of patients. Conclusions. The presence of concomitant hypertension in patients with NAFLD was associated with more active progression compared to patients with isolated NAFLD. Correlation analysis showed gradual exhaustion of anti‑inflammatory protection and increase of pro‑inflammatory activity as changes in liver parenchyma progressed, especially in patients with comorbid NAFLD and HTN course. That allows us to consider HTN as a prognostically unfavorable risk factor for the development and progression of the liver parenchyma fibrosis.