Markers of liver damage in comorbidity of nonalcoholic liver disease and hypertension

Abstract

Objective: to study the features of liver damage and to study the main factors of influence on this process with comorbidity between non-alcoholic fatty liver disease and essential hypertension or renoparenchymal arterial hypertension. Materials and methods. The object of the study was 269 patients, included in three groups: group 1 - patients with non-alcoholic fatty liver disease (60 patients), group 2 - patients with comorbidity of non-alcoholic fatty liver disease and essential hypertension (121 patients), group 3 - patients with comorbidity of non-alcoholic fatty liver disease and renoparenchymal arterial hypertension (88 patients). The control group consisted of 20 healthy individuals of the same age and gender categories. Clinical examination of patients included an assessment of the parameters of an objective examination: in particular, anthropometric data and blood pressure according to standard methods. We studied both laboratory and instrumental markers of liver damage. To diagnose the condition of the liver and blood vessels in all patients, an ultrasound method was used. Some patients (212 people) underwent the Fibromax test. To assess the severity of insulin resistance, the HOMA index was calculated. Glomerular filtration rate was determined by the formula CKD-EPI. The level of cytokeratin-18 in blood plasma was determined by ELISA. Results and its discussion. A highly significant difference was found for most indicators between the groups of patients and the control group. The greatest difference was found in levels of transaminases (ALT and AST), gamma-glutamyl transpeptidase, as well as cytokeratin-18 (p <0.001). The most pronounced increase in transaminases was observed in patients of group 3. The levels of gammaglutamyltranspeptidase in patients of all three groups significantly exceeded the corresponding parameters of the control group, were the highest in group 3 - 68.10 ± 33.31 U/l. Moreover, this the indicator did not significantly differ between groups 2 and 3 (p> 0.05). Cytokeratin-18 was significantly increased in patients with nonalcoholic fatty liver disease, and was significantly different between all groups. Fewer patients with no hepatic fibrosis were recorded in group 1. We found significant correlation between the duration of non-alcoholic fatty liver disease and all markers of liver damage in group 1. Also, markers of liver damage positively correlated with body mass index, which indicates an important role obesity in the pathogenesis of non-alcoholic fatty liver disease. Given the correlations with the indicators of adiponectin, malondialdehyde, tumor necrosis factor-alpha, HOMA, we can state the important role of inflammation, oxidative stress, insulin resistance in the pathogenesis and development of non-alcoholic fatty liver disease. A strong negative correlation between cytokeratin-18 and glomerular filtration rate of - 0.402 (p <0.001) was also found. Important in our opinion were the positive relationships between indicators of hepatic damage and blood pressure in groups 2 and 3, which may indicate a relationship within comorbidity. In general, the largest number of strong correlation bonds were found for cytokeratin-18, and the smallest for gammaglutamyltranspeptidase. The profile of the correlation between the main indicators did not differ much from group 2. Using ANOVA dispersion analysis, we found a close relationship between the degree of liver steatosis and the main markers of liver damage ALT, AST, GGT, cytokeratin-18, fibrotest, and actitest. The highest Fisher coefficient was recorded for cytokeratin-18 - F = 118.58 (p <0.001), actitest - F = 102.18 (p <0.001), fibrotest - F = 95.03 (p <0.001), gamma-glutamyltranspeptidase - F = 26.6 (p <0.001). Such data indicate a close relationship between the processes of fat accumulation, inflammation, and apoptosis in the liver with non-alcoholic fatty liver disease in the presence or absence of comorbidity with essential hypertension or renoparenchymal arterial hypertension. Conclusions. For patients with non-alcoholic fatty liver disease, in the presence of its comorbidity with essential hypertension or renoparenchymal arterial hypertension, a more pronounced increase in gamma-glutamyl transpeptidase, cytokeratin-18 and actitest was characteristic, which may indicate the presence of more active processes of inflammation and hepatic apoptosis. A negative effect of comorbidity with essential hypertension or renoparenchymal arterial hypertension on liver fibrosis was also found. Markers of liver damage are associated with the duration of non-alcoholic fatty liver disease activity, body mass index, adiponectin, markers of inflammation and oxidative stress, kidney function. The degree and list of correlation relationships differ with non-alcoholic fatty liver disease depending on the presence or absence of comorbidity with essential hypertension or renoparenchymal arterial hypertension. Severe liver steatosis strongly affects the processes of hepatic inflammation, fibrosis and apoptosis with the comorbidity of non-alcoholic fatty liver disease with essential hypertension or renoparenchymal arterial hypertension.