Manifestation Of Liver Fibrosis Research Articles

The Effect of Retinol Acetate on Liver Fibrosis Depends on the Temporal Features of the Development of Pathology

The effect of vitamin A on the manifestations of liver fibrosis is controversial and establishing the causes of its multidirectional influence is an urgent problem. In the work, the functional characteristics of the liver with Cu-induced fibrosis were determined after the restoration of vitamin A to the control level at the F0/F1 stage. In animals with liver fibrosis, classical indicators of physiology, functional activity of the liver, histological, and hematological characteristics were determined; the content of calcium and ROS was determined in bone marrow cells. It was shown that in the liver with Cu-induced fibrosis, the restoration of vitamin A content to control values after per os injections of a retinol acetate solution at a dose of 0.10mg (300 IU)/100g of body weight in the early stages of this pathology development (Fо/F1) was accompanied by: a decrease in the number of immunocompetent cells in the bloodstream to control values; normalization of the amount of calcium ions and ROS in bone marrow cells; restoration to the control level of activity of alkaline phosphatase; an increase in the number of binuclear hepatocytes; and restoration of the dynamics of body weight growth in experimental animals, even against the background of the ongoing action of the hepatotoxic factor. We came to the conclusion that the multidirectional action of vitamin A, which occurs in liver fibrosis, depends not only on the concentration of vitamin A in the liverbut also on temporal characteristics of cellular and metabolic links involved in the adaptive response formation. It was suggested that knowledge of the initial temporal metabolic characteristics and the amount of vitamin A in the liver, taking into account the stages of fibrosis development, can be an effective way to restore the altered homeostatic parameters of the body.

Hepatic fibrosis as an additional risk factor for the development of cardiovascular disorders in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease

The aim of the study was to determine the relationship between the degree of progression of liver fibrosis and the risk of cardiovascular complications in patients with Type 2 diabetes mellitus (DM) with non-alcoholic fatty liver disease (NAFLD). The study included 110 patients with Type 2 diabetes (62 men and 48 women), the average age of the subjects was 52.07±1.11 years. All patients were divided into 2 groups: the main group included 72 patients with Type 2 diabetes with concomitant NAFLD (38 men and 34 women); the control group included 38 patients with Type 2 diabetes without clinical manifestations of NAFLD (24 men and 14 women). Patients of the main group were divided into 3 subgroups, taking into account the predominant pathological processes in the clinical picture. The division into subgroups was carried out in 2 stages: at the first stage, those with predominant manifestations of liver fibrosis (F2 or more) were selected from the general population of patients with Type 2 diabetes with NAFLD according to the results of liver elastography and the use of Bonacini and Metavir scales. The number of such patients was 29, which accounted for 40.3% of the total number of patients in the main group. The remaining patients were divided into 2 subgroups: 11 patients (15.3%) had non-alcoholic liver steatosis, and 32 patients (44.4%) had signs of non-alcoholic steatohepatitis (NASH). As a result of the study, it was found that the presence of liver fibrosis in patients with Type 2 diabetes with NAFLD is significantly more often associated with cardiovascular complications, such as arterial hypertension, coronary heart disease, myocardial infarction, stroke, diabetic retinopathy and nephropathy. A significant decrease in the ejection fraction (EF) was found in patients with Type 2 diabetes with concomitant NAFLD. At the same time, the number of patients with EF disorders of varying degrees in the main group significantly exceeded that in the comparison group (33.3% and 6.7%, respectively, p<0.001). The average values of left ventricular myocardial mass are significantly lower in patients with NASH and fibrosis formation compared to patients with NAFLD at the stage of fatty hepatosis. There was also a significant decrease in the size of the left and right atria in patients with NASH compared to both patients with steatosis and patients with fibrotic liver changes. Patients with predominant fibrotic changes in the liver are characterized by a relative decrease in myocardial mass, a decrease in final diastolic and systolic volumes and EF, which may indicate the development of diastolic dysfunction in them. It is shown that it is necessary to take into account in clinical practice not only the generally accepted stages of NAFLD, but also the predominant pathological process in the liver in patients with Type 2 diabetes, namely steatosis, manifestations of inflammation and fibrotic disorders. It is proved that fibrotic changes in the liver can develop at all stages of liver tissue damage.

Hepatoprotective Impact of Geraniol Against CCl4-Induced Liver Fibrosis in Rats.

Numerous experimental studies have shown various pharmacological activities including geraniol's cancer prevention agent and antioxidant capacity. The goal of this investigation is to mark the prospective defensive role of geraniol in rat's carbon tetrachloride (CCl4) instigated in liver fibrosis. Liver fibrosis was prompted by subcutaneous injections of CCl4, twice week by week and for about a month. Simultaneously, geraniol (200 mg kg-1) was orally regulated every day. Post-Hoc-Test were carried out where p<0.05 has been established as a significant value. The biochemical results showed that geraniol reduced liver damage just as manifestations of liver fibrosis. The administration of geraniol diminished the CCl4-initiated the elevation in serum aminotransferase activities and alkaline phosphatase activity. Geraniol diminished the levels of TNF-α, NO and myeloperoxidase activity which were prompted by the CCl4 treatment. The rise of serum hyaluronidase activity and hepatic hydroxyproline content was also curtailed by geraniol treatment. Besides, geraniol fundamentally declined hepatic malondialdehyde (MDA) formation and increased reduced glutathione (GSH) in CCl4-treated rats. Geraniol has also increased the activity of hepatic antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) in the rats treated with CCl4. Finally, the histological analysis of the liver bolstered the biochemical results. Our study has demonstrated that geraniol has a hepatoprotective upshot on liver fibrosis caused by CCl4, supposedly due to its free radical scavenging, antioxidant and anti-inflammatory characteristics.

Ultrasound hepatic elastography with decaying signal technology allows assessing the degree of steatosis and dynamic monitoring of the effectiveness of NAFLD treatment

The purpose of the research is to study the informativeness of the technology of Controlled Attenuation Parameter (CAP) in Shear Wave Elastography (SWE) in determining the degree of severity of liver steatosis depending on the elastometric quantitative values of liver fibrosis in a one-time study in a given volume of parenchima liver in patients with non-alcoholic fatty liver disease (NAFLD).Materials and methods of research. The study included 169 patients with NHTSA between the ages of 19 and 81, the average age was 41.7 ±11.3 years, examined in the “City Clinical Hospital No. 1” of the Ministry of Health, Chuvashia (Cheboksary, Russia). Patients with functional disorders of bile evacuation (n= 72) were the first group; the 2nd group were the patients with liver steatosis without manifestations of liver fibrosis (n = 28); the 3rd contained the patients with cirrhosis of the liver (n = 25); patients with chronic viral hepatitis B and C (n= 44) were in the 4th group. All patients were screened with ultrasonic shear wave elastography with elastometry in one-dimensional (TE) (FibroScan 502 TOUCH, France) and two dimensional (2DSWE) modes (Aixplorer, Supersonic Imagine, France). Elastometry (kPa) and steatometry (dB/m) were completed simultaneously within the same volume of the analyzed liver tissue with two sensing devices of “FibroScan 502 TOUCH”. The statistical processing was carried out with the help of IBM SPSS Statistics 10.0. The results are reflected in the form of median (Me), minimum (min), maximum (max) and medium (Emean) values, standard deviation (SD) of Jung’s elasticity module. Correlational analysis of the received values of parameters F and S was made with the descriptive method of Bland-Altman and the method of Spearman.Results and discussion. The average quantitative values of the severity of liver steatosis in patients with cirrhosis of liver had reliably lower values (234.5±62.1 dB/m) than in those suffering from steatosis of the liver without fibrosis (347.5±37.6 dB/m) and patients with chronic viral hepatitis (245.9±57.3dB/m, p lt; 0.001). The values of fibrosis in the same amount of the tested liver tissue with liver cirrhosis (45.5± 22.3 kP) were higher than similar rates in the other groups of patients with NAFLD (p lt; 0.001). Diagnostic informational content of the method of controlled ultrasound attenuation in establishing the degree of manifestation of liver steatosis had a higher specificity with II degree of liver steatosis (99.29% with a sensitivity of 84.92%).The results of the study allow us to recommend ultrasound elastography with the technology of controlled ultrasound attenuation to determine the severity of liver steatosis for both primary diagnosis and for dynamic monitoring of the liver condition of patients with NAFLD.

Connexin32 deficiency exacerbates carbon tetrachloride-induced hepatocellular injury and liver fibrosis in mice

Objective: Liver fibrosis results from the perpetuation of the normal wound healing response to several types of injury. Despite the wealth of knowledge regarding the involvement of intracellular and extracellular signaling pathways in liver fibrogenesis, information about the role of intercellular communication mediated by gap junctions is scarce.Methods: In this study, liver fibrosis was chemically induced by carbon tetrachloride in mice lacking connexin32, the major liver gap junction constituent. The manifestation of liver fibrosis was evaluated based on a series of read-outs, including collagen morphometric and mRNA analysis, oxidative stress, apoptotic, proliferative and inflammatory markers.Results: More pronounced liver damage and enhanced collagen deposition were observed in connexin32 knockout mice compared to wild-type animals in experimentally triggered induced liver fibrosis. No differences between both groups were noticed in apoptotic signaling nor in inflammation markers. However, connexin32 deficient mice displayed decreased catalase activity and increased malondialdehyde levels.Conclusion: These findings could suggest that connexin32-based signaling mediates tissue resistance against liver damage by the modulation of the antioxidant capacity. In turn, this could point to a role for connexin32 signaling as a therapeutic target in the treatment of liver fibrosis.