Background. In recent years, as a result of the growing expansion of the pharmaceutical market, there has been a clear trend towards an increase in the incidence of chronic toxic drug-induced hepatitis of drug genesis (TDIH). The appearance of fibrosis is considered the most important histological change that determines the further course of the disease. Therefore, the search for non-invasive or minimally invasive markers for assessing fibrotic changes in the liver remains an urgent issue in clinical practice. The purpose was to determine the diagnostic value of immunological parameters for stratification of the severity of liver fibrosis in patients with TDIH. Materials and methods. The study included 41 patients with TDIH, who were divided into three groups: group I consisted of 12 people without liver fibrosis (F0), group II — 22 patients with moderate fibrosis (F1-F2), group III — 7 individuals with severe liver fibrosis (F3-F4). Shear wave elastography was performed using a Soneus P7 system (Ukraine-Switzerland). All patients underwent a biochemical blood test with the determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST). The subpopulation composition of lymphocytes, circulating immune complexes (CIC), the level of interleukins (IL-6, IL-10) and tumor necrosis factor α were assessed. Results. The progression of liver fibrosis is accompanied by an increase in cytolytic syndrome: patients with severe fibrosis have a 3.3-fold increase in the ALT (p < 0.05) compared to the controls and a 2.1-fold (p < 0.05) compared to that in patients with moderate fibrosis. The AST level is significantly higher — by 4.6 times (p = 0.023) in patients with severe fibrosis than in those with moderate fibrosis. With the progression of liver fibrosis, there is a significant decrease in cellular immunity, an increase in the level of CIC and pro-inflammatory cytokines with a simultaneous decrease in the content of anti-inflammatory cytokines, which is confirmed by correlations between the liver stiffness index according to shear wave elastography data and the level of T-helpers (r = –0.466; p = 0.03), IL-6 (r = 0.364; p = 0.01), IL-10 (r = –0.331; p = 0.039) and CIC (r = 0.381; p = 0.017). Conclusions. Markers of the diagnosis of severe liver fibrosis in patients with TDIH are indicators such as the ratio of IL-6/IL-10 higher than 0.83 (sensitivity 81.8 %, specificity 78.9 %), CIC level more than 4.3 optical density units (sensitivity 77.3 %, specificity 72.2 %), the ratio of T-helpers/T-suppressors is less than or equal to 1.6 (sensitivity 72.7 %, specificity 57.9 %).
Background. Non-alcoholic fatty liver disease (NAFLD) ranks first among chronic liver diseases and covers almost a quarter of the population. Enough data have been accumulated on the mutual influence of metabolic changes and steatosis of the liver of varying degrees on the existence and progression of each other. The coexistence of non-alcoholic steatohepatitis (NASH) with various comorbidal conditions has already been recorded in many studies, a direct relationship has been determined between the presence of fatty degeneration and various components of the metabolic syndrome — arterial hypertension, type 2 diabetes, obesity and dyslipidemia. The purpose was to determine the relationship between carbohydrate and fat metabolism in patients with NAFLD depending on the degree of fat accumulation in the liver. Materials and methods. Data were obtained from 72 patients with NAFLD, who were divided into two groups according to the degree of steatosis. The I group included 46 patients with moderate steatosis (the proportion of hepatocytes containing fatty is 33–66 %). The indicator of the controlled parameter of ultrasonic attenuation (CAP) ranged from 232 to 256 dB/m. The II group consisted of 26 patients with severe steatosis (the proportion of hepatocytes containing fatty inclusions more than 66 %), with CAP more than 256 dB/m. The trophological status, the parameters of carbohydrate and fat metabolism were determined. A statistical analysis of the data was carried out — the mean values in the groups were compared and the contribution of variables to the value of CAP was estimated using the method of multiple regression analysis. Results. The level of insulin and HOMA-IR in patients with severe fatty degeneration of the liver was (22.7 ± 9.7) and (5.4 ± 2.7) μU/ml, respectively. These indicators were higher than the corresponding indicators of group I (p < 0.05), (17.1 ± 10.3) and (4.01 ± 2.9) μU/ml for insulin and HOMA-IR, respectively. Glucose, lipid spectrum did not differ significantly between the groups, except for the fraction of very-low density lipoproteins (VLDL), which were significantly higher in patients with a higher degree of fatty degeneration and amounted to 3.4 (2.3–4.1) and 3.0 (2.4–3.8) mmol/L in groups II and I, respectively. Multiple regression analysis was performed to determine the contribution of fat and carbohydrate metabolism to CAP values. As a result of step-by-step analysis, two indicators remained in the model, namely the HOMA index (regression coefficient β 5.285, p = 0.04) and BMI (regression coefficient β 4.666, p = 0.001). It was determined that changes in BMI and HOMA are responsible for 31 % of changes in the value of CAP. Conclusions. Insulin values, HOMA index, BMI and VLDL are higher in patients with severe steatosis. According to the results of multiple regression analysis, a significant contribution of HOMA and BMI values to the CAP was revealed.
Background. The purpose of the study is to investigate the peculiarities of lipid and carbohydrate metabolism in patients with gastrointestinal diseases depending on the body mass index (BMI). Materials and methods. Forty patients with digestive disorders were examined, 13 women (32.5 %) and 27 men (67.5 %) whose median age was 37 (24; 51) years. The patients were divided into 3 groups: I — 20 people with BMI exceeding the norm; II — 11 patients with a BMI below the norm; III — 9 patients with normal BMI. The control group for evaluating the results of laboratory tests consisted of 15 practically healthy people. Total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), glucose and insulin serum levels were evaluated. The atherogenic index (AI) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were calculated. Statistical processing of the results was carried out using the Statistica 6.1 software package. Results. In patients with digestive diseases who had an increased BMI, the development of atherogenic dyslipidemia was detected, as indicated by a probable decrease in serum content of HDL-C by 1.7 times (p = 0.003) and an increase in TG by 1.9 times (p = 0.002), VLDL-C by 1.4 times (p = 0.05), AI by 2 times (p = 0.03) compared to the controls. No significant signs of the development of atherosclerotic processes were found in patients with reduced and normal BMI. Carbohydrate metabolism disorders were observed in 47.5 % of patients with gastrointestinal diseases, and HOMA-IR in patients with increased BMI was 2.9 times higher (p < 0.05) compared to those with reduced BMI and 2.5 times (p < 0.05) higher — with normal BMI. It was found that an increase in BMI is associated with an increase in serum TG (r = 0.381; p = 0.017), LDL-С (r = 0.383; p = 0.016), AI (r = 0.566; p < 0.001), insulin (r = 0.651; p = 0.0001) and HOMA-IR (r = 0.681; p = 0.0001), as well as that BMI is negatively correlated with the content of HDL-С (r = –0.448; p = 0.004). At the same time, an inverse correlation was found between HOMA-IR and the level of HDL-С (r = –0.389; p = 0.016), and a direct relationship between the index of insulin resistance and AI (r = 0.437; p = 0.006). Conclusions. The revealed correlations confirm the hypothesis of the BMI influence on the development of dyslipidemia and insulin resistance in patients with gastrointestinal diseases. This substantiates the expediency of including bioimpedance measurements into the algorithm for predicting metabolic disorders in this category of patients.
The aim of our research was to obtain new minimally invasive serum markers of fibrotic changes of liver in patients with chronic diffuse liver diseases of different etiology and compare them with traditional markers. 364 patients aged 30 to 66 years were examined: 221 women (60.7%) and 143 men (39.3%). Depending on the etiological factors, all patients were divided into 4 groups: group I consisted of 108 patients with non-alcoholic fatty liver disease (NAFLD), group II – 143 patients with chronic hepatitis associated with virus C (CHC), group III – 56 patients with alcoholic liver disease (ALD), group IV – 57 patients with toxic drug-induced hepatitis (TH). The control group consisted of 30 practically healthy people. Using correlation and ROC-analyzes, we obtained minimally invasive diagnostics markers that show the risk of developing liver fibrosis. For patients with NAFLD these were the levels of HOMA-IR, TNFα/IL-10 and α1-acid glycopeptide content, which are better in quality of the diagnostic model than the traditional Forns index, APRI, FIB-4, AAR. For patients with CHC, these were the protein-bound hydroxyproline (HPp/b) /HPf ratio, phospholipids content, and IL-6, CD4+ levels, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. The following markers were obtained for patients with ALD – TNFα levels, HPp/b and glycosaminoglycans content, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. For patients with TH, these were medium molecular weight peptides content, IL-6/IL-10 ratio and CD4+/CD8+, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. Thus, new minimally invasive markers of fibrosis in patients with chronic diffuse liver diseases have been obtained.
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