The main pathogenetic aspects of non-alcoholic fatty liver disease as a comorbid factor of chronic hepatitis C are considered. Non-alcoholic fatty liver disease is currently the most common liver disease worldwide, both among adults and children. It is usually accompanied by obesity, insulin resistance and diabetes mellitus. Non-alcoholic fatty liver disease includes a spectrum of pathologies from simple fatty liver infiltration to non-alcoholic steatohepatitis, which is characterized by inflammation with potential progression to fibrosis and cirrhosis over time. On average, non-alcoholic fatty liver disease occurs in 55% of patients with chronic hepatitis C, which is significantly higher than the prevalence of each disease individually. This condition leads to a greater rate of progression of fibrosis, as well as a continuing high risk of developing cirrhosis and hepatocellular carcinoma even after achieving a sustained virological response. In this regard, complex therapy aimed at normalization of the nutritional status, optimization of body weight, correction of impaired intestinal microflora, reduction of severity of liver steatosis and achieving a sustained virological response is a priority task in the treatment of patients with chronic hepatitis C.
Chronic hepatitis C remains one of the most important socially significant infections for world health. The use of modern highly effective drugs with direct antiviral action allowsto achieve a sustained virological response in patients. At the same time, in a significant number of cases after elimination of HCV infection, the progression of fibrosis continues with the development of its terminal stages and an unfavorable outcome for patients. The article focuses on comorbid pathology, which is a leading factor in this process in patients with chronic hepatitis C who have achieved a sustained virological response and presenting a serious challenge to modern hepatology.
BACKGROUND: The main pathogenetic aspects of the correction of cognitive impairment of the brain and antifibrotic therapy against the background of experimentally induced severe fibrosis and cirrhosis of the liver in rats are considered. Viral hepatitis of various etiologies is one of the main problems of modern health care. The incidence of viral hepatitis is 30 million cases per year. Mortality from complications of acute viral hepatitis, such as cirrhosis of the liver and hepatocellular carcinoma, reaches 1.4 million cases per year. At the same time, in some cases, etiotropic therapy does not provide stabilization or regression of fibrotic changes in the liver tissue in comorbid patients, as well as in patients receiving antiviral therapy at the stages of severe fibrosis and compensated liver cirrhosis, which requires the search for new therapeutic approaches related to, first of all, with the possibility of influencing non-specific processes of fibrogenesis. Hepatic encephalopathy in such patients leads to the appearance of behavioral, cognitive and motor disorders of varying severity, thereby having a negative impact on the operators function in such professions as pilots, dispatchers, in a number of military specialties, etc. Thus, therapy aimed at the key links of pathogenesis often plays a decisive role in the treatment of liver diseases, especially in the later stages. AIM: To identify the presence and severity of cognitive impairment in rats with induced severe liver fibrosis and liver cirrhosis before and after therapy with Bicyclol and to assess the degree of its antifibrotic effect. MATERIALS AND METHODS: The study included 70 male Wistar rats weighing 180200 g, in which toxic fibrosis and cirrhosis of the liver were induced at stages F3 and F4. The control group consisted of 10 individuals who received a normal diet, the experimental group 24, who, in addition to the standard diet, were prescribed the drug Bicyclol. The assessment of cognitive impairment of the brain was carried out using a test with a hidden platform in the Morris water maze and statistical analysis. The evaluation of the results of the use of the drug was carried out using histological examination, methods of biochemical, molecular biological and statistical analysis. RESULTS: The use of the drug Bicyclol leads to a marked decrease in fibrotic changes in the liver tissue of experimental animals and was accompanied by a temporary decrease in the activity of alanine aminotransferase in blood serum. Against the background of the development of induced toxic fibrosis and cirrhosis of the liver in rats, cognitive dysfunctions of the brain were observed, which significantly decreased against the background of the use of the drug Bicyclol. CONCLUSION: Results The use of bicyclol for 4 weeks in laboratory animals with induced severe liver fibrosis led to a long-lasting decrease in the severity of fibrotic changes in liver tissue, as well as to the regression of cirrhosis in rats with liver cirrhosis. These changes were accompanied by a decrease in cognitive impairment in rats of these subgroups, as evidenced by an improvement in the estimated indicators when performing a control complex in a Morris water maze with a hidden platform.
The aim of the study was to assess the possibilities of noninvasive diagnosis of liver fibrosis (FIB-4 and APRI indices) in patients with CHC and abdominal obesity.Materials and methods. 52 men with CHC were examined. Genotype 1 was determined in 24 patients, genotype 3 in 19 patients and genotype 2 in 9 patients. According to the severity of fibrosis, patients with CHC were divided: without fibrosis (F0) - 12 patients, with weak fibrosis (F1) - 17 patients, with moderate fibrosis (F2) - 10 patients, with severe fibrosis (F3) - 8 patients, cirrhosis of the liver (F4) was detected in 5 patients. According to a liver biopsy, steatosis was found in 18 patients with CHC. Abdominal obesity was found in 34 patients with CHC. Non-invasive diagnosis of liver fibrosis was assessed using routine FIB-4 and APRI indices. The interval of values of FIB-4 and APRI, not related to the criteria for assessing the stage of fibrosis F3 and F4, we have conventionally designated as the «gray zone». The presence of insulin resistance was evaluated at HOMA-IR> 2.Results. Key values of the FIB-4 index in patients with CHC and abdominal obesity were found significantly more often than when calculating the APRI index. Insulin resistance in patients with CHC and abdominal obesity was statistically significantly more frequent than in patients with CHC and without abdominal obesity. At stages F3-F4 in patients with CHC, abdominal obesity and insulin resistance, APRI values were recorded more often in the «gray zone»than FIB-4 values.Conclusion. The FIB-4, APRI, HOMA-IR indices can be used in patients with CHC and abdominal obesity during the follow-up and dynamic monitoring of patients with CHC to highlight risk groups. FIB-4 was significantly more informative for determining the stage of fibrosis than APRI in patients with CHC and abdominal obesity with insulin resistance (HOMA-IR> 2).
Background and aims: to estimate concentration of sMadCAM-1 in peripheral blood at patients with chronic hepatitis C with excess body weight.Materials and methods: The research included 88 patients (67 men, 21 women 41.4±3.2 years of age) with chronic hepatitis C (CHC) and excess body weight (the index of body mass is ³25 kg/m2, and abdominal circumference more than 94 cm in men, and 80 cm in women) with various morfofunktsionalny changes in a liver and a small bowel. From them men there were 67 people, women – 21, middle age was 41.4±3.2 years.To all the patients complex clinical, biochemical, virologic, morphological trial was carried out. The functional condition of intestines was estimated by identification of a small intestinal bacterial overgrowth (SIBO) when carrying out the hydrogen respiratory test (HRT) with lactulose and existence of endoscopic signs of inflammation of a mucous membrane of intestines at a fibroezofagogastroduodenoskopiya. The quantitative assessment of a mucosal addressin cell adhesion molecule -1 was carried out by the definition concentration of its soluble form (sMadCAM-1) in a blood plasma by enzyme immunoassay method.Results: the sMadCAM-1 level of peripheral blood at the patients with excess body weight increased in process of progressing of a stage of chronic hepatitis C (F0 – 349.10 (324.27-373.92) ng/ml; F1/2 – 439.69 (406.43-472.94) ng/ml; F3/4 – 1057.82 (593.38-1522.26) ng/ml; p˂0.05), existence of a syndrome of excess bacterial growth and endoscopic signsof a duodenitis. Besides, patients had its concentration more with the biochemical signs characterizing cytolytic (at ALT˃N: 502.54 (432.04-573.03) ng/ml against 381.04(345.49-416.58) at the ALT normal values), cholestatic (at GGTP˃N: 550.59 (453.31-647.88) ng/ml against 400.86(365.13-436.59) atnormal GGTP, p values 0.05; at ALP N: 572.2 (353.7-790.8) ng/ml against 468.7 (408.5-528.9) ng/ml at normal ALP, p values 0.05) and metabolic syndromes (at glucose of blood, TG, VLDL N: 562.93 (369.59-756.27) ng/ml, 681.15 (387.81-974.49) ng/ml, 809.65(124.04-1495.28) against (438.34(391.36-485.31) ng/ml), (421.69(379.41-463.97) ng/ml), 434.47(389.45-479.48), p values 0.05 at normal values of these indicators respectively). Conclusion: Progressing of fibrosis and functional disturbances in intestines are interconnected with increase in concentration of MadCAM-1 in blood that allows to consider pathological changes in intestines of various genesis as the accessory factor promoting progressing of СHC at patients with excess body weight. Besides, definition of concentration of sMadCAM-1 in peripheral blood can be used as one of markers of noninvasive diagnostics of a stage of fibrosis at the patients with СHC and excess body weight.
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