THE HEPATOPROTECTOR ROPREN FOR THE TREATMENT OF PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS: A PROSPECTIVE OBSERVATIONAL STUDY.

OBJECTIVES: New and effective drugs to improve liver function and fibrosis are urgently needed for patients with nonalcoholic steatohepatitis (NASH). This study examines the effectiveness of treatment of patients with NASH with the registered heparoprotector, Ropren~ Methods. This observational study used Ropren? in a post-registration setting to treat 20 females (38-56 years) with chronic NASH unresponsive to standard treatment. Ropren? is a biopolymer made up of polyprenols (analogue of dolichol) isolated from the green verdure of spruce (Picea abies (L) Karst). Ropren? was given orally, three times a day (54 mg/day). Measurements before and after treatment included symptoms and blood biochemistry (triglycerides, high-density lipoproteins, low-density lipoproteins, alanine transaminase, aspartate transaminase, alkaline phosphatase and gamma-glutamyl-transpeptidase). Liver fibrosis was measured with indirect ultrasound elastometry. RESULTS: After 12 weeks of Ropren? treatment, improvements were found for blood lipids and clinical and biochemical signs, including reductions in total cholesterol and triglycerides (p <0.05). Ropren® also significantly decreased the liver fibrosis index (p <0.05). No side effects were observed. CONCLUSIONS: Ropren® treatment increased the elasticity of the liver and might be useful to reduce the risk of cirrhosis. Although the sample size in this study was small, the results demonstrated that a randomised-controlled trial of Ropren? for NASH is warranted.

[WILSON'S DISEASE (HEPATOLENTICULAR DEGENERATION, DYSTROPHIA HEPATOCEREBRALIS) DIAGNOSIS, TREATMENT AND DISPENSARY OBSERVATION. GUIDELINES WERE APPROVED BY THE XV GASTROENTEROLOGICAL SCIENTIFIC SOCIETY OF RUSSIA IN 2015].

Wilson's disease (hepatolenticular degeneration, dystrophia hepatocerebralis)--a chronic, progressive disease with a genetically determined autosomal recessive mode of inheritance. The violence in metabolism of copper with its excessive accumulation in visceral organs and central nervous system is the basis of the disease. The guidelines on clinical diagnosis and management of patients based on a Review and analysis of recent publications on this topic in the global and Domestic literature and on the authors' experience in treating patients with Wilson's disease.

[Diagnostic value of serum markers of fibrosis in chronic liver diseases].

AIM: To estimate the diagnostic value (DV) of direct markers of liver fibrosis, such as type IV collagen (C-IV), hyaluronic acid (HA), tissue inhibitor of metalloproteinases-1 (TIMP-1) in combination with indirect markers of fibrosis, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (gamma-GTP), alkaline phosphatase (ALP), platelets, tumor necrosis factor-alpha (TNF-alpha) in evaluating liver fibrosis. SUBJECTS AND METHODS: Sixty-seven patients with chronic diffuse liver diseases were examined. ALT, AST, gamma-GTP, and ALP were determined as indirect indicators of fibrosis. The levels of TIMP-1, HA, C-IV, and TNF-alpha were estimated by ELISA; the stage of fibrosis was determined by the results of indirect liver ultrasound fibroelastography (FE). RESULTS: According to the results of FE, the patients were divided into 2 groups: 1) (n = 25) F < or = 2 METAVIR and 2) (n = 42) F3-F4. While estimating DV of severe fibrosis stages (F3-F4), the area under the ROC curve (AUC) increased for platelets, HA, and C-IV. DV of ALT, AST declined with the higher degree of fibrosis. The highest ratio of test specificity and sensitivity (TSp and TSen) and AUC were observed for AST and HA. ALT and platelets showed low TSen, and TNF-alpha and TIMP-1 had no TSp. For evaluation of fibrosis (F4), a HA increase of over 57.7 ng/ml had 92.6% TSen and 67.5% TSp; for a C-IV elevation of above 133.1mkg/l, TSen was 85.2%, TSp was 57.5%; for a TIMP-1 rise from 24.4 ng/ml, TSen was 74.1% and TSp was 62.5%. For the diagnosis of fibrosis (F4) with a HA rise of more than 57.7 ng/ml, DV of a positive test was 65.8 (48.65-80.4; 95% CI) and that of a negative test was 93.1 (76.8-99.2; 95% CI). Thus, the negative rather than positive test results are of great diagnostic value for evaluation of the degree of fibrosis. CONCLUSION: The results of the investigation convincingly suggest that examination of the serum markers of fibrosis allows one to estimate with a high probability its presence and severity in patients with hepatic cirrhosis. The so-called direct markers (substances reflecting the biochemistry and regulation of fibrogenesis) are undoubtedly of great diagnostic value.

[Realities and prospects for the use of cell technologies for the treatment of chronic diffuse liver diseases].

Chronic liver disease (CLD) leads to disability annually hundreds of thousands of patients worldwide. Originating as a rule, at a young age (20-40 years), they are always significantly degrade the quality of life of patients, making them socially significant. Moreover, the conventional treatment (hepatoprotectors, antiviral drugs, corticosteroids, immunosuppressive medication) not always lead to achieving the desired effect, and therefore is constantly searching for alternative treatments. Cell therapy with embryonic fetal, mononuclear, mesenchymal stromal cells is the most advanced front of modern biotechnology and medicine. Using the SC with the purpose of treatment in chronic liver diseases is the possibility of disturbed regulation of cell-cell interactions in the liver, the impact on the mechanisms of cell death (necrosis - apoptosis) and fibrogenesis, which makes this method the most relevant and promising in hepatology. The article presents an analysis of the results of studies conducted in the field of stem cell technologies by leading domestic and foreign scholars in the treatment of liver diseases. Were studied questions of transdifferentiation, the mechanisms of stem cells in hepatology, as well as the possible risks of this therapy (pro-oncogene action, increased fibrosis). Also was presented our own experience of applying cellular technology in experimental models of acute toxic hepatitis in animals.

[Treatment and prevention of portal hypertension in patients at elderly and senile patients].

The most significant complication of cirrhosis is portal hypertension syndrome. Varicose veins of the esophagus and stomach diagnosed in 50 - 80% of patients with liver cirrhosis and complicated by hemorrhage in 30 - 50%. Course, treatment and management of patients with portal hypertension in elderly people is poorly understood.

[Features of the HCV-infection in the elderly patients].

The problem of chronic HCV-infection in the elderly patients is poorly known. During the HCV-infection and progression of fibrosis in chronic liver diseases depends on age of the patient.

[Effectiveness of the new plant hepatoprotector--Ropren in patients with non-alcoholic steatohepatitis].

Liver damage causes serious metabolic disorders, immune response, detoxification functions and antimicrobial protection. Therefore, the problem of finding new high effective drugs for the restoration and normalization of liver function is extremely urgent. This article presents a new domestic plant hepatoprotector Ropren, which is a biopolymer polyprenols isolated from the green of pine and spruce, and an analog of the endogenous lipid--dolichol. Presented the Ropren efficiency in patients with nonalcoholic steatohepatitis. The drug reduces the clinical and biochemical disease activity, contributes to the normalization of lipid profile. The resulting decrease in the index treatment of fibrosis, determined by indirect transient elastometry, indicates an increase in the elasticity of the liver and reducing the risk of developing cirrhosis.

[The diagnostic significance of ultrasound elastometry in evaluation of fibrosis in chronic diffuse liver diseases].

THE PURPOSE OF THE STUDY: Determination of the diagnostic value of ultrasound elastometry of liver (UEL) in the assessment of liver fibrosis in patients with chronic diffuse liver diseases (CDLD). MATERIAL AND METHODS: The study involved 316 patients with various etiologies of the CDLD, with the underwent both liver biopsy, the UEL, and evaluation of fibrosis (F) according to the Metavir classification. RESULTS: The maximum diagnostic accuracy of the UEL was obtained in determining of the 4-th stage of fibrosis according to the Metavir. The accuracy of the method was 91% with a sensitivity of 100%. The lowest sensitivity of the UEL determined in patients with nonalcoholic fatty liver disease (NAFLD): F1 - 25%, F2 - 33%, F3 and F4 - 50%. The High body mass index (BMI = 30,1 +/- 3,8 kg/m2) is a factor which is limiting the use of elastometry for patients NAFLD. The low sensitivity for F1 and F2 - 14,3% and 10%, respectively, 100% for F4, with a BMI = 24,4 +/- 5,1 kg/m2 was obtained in primary biliary cirrhosis (PBC). In the alcoholic liver disease (ALD) obtained high sensitivity (100%) for F2 and F4. In the CDLD of viral etiology the sensitivity of UEL was 33-71,4% in the early stages of fibrosis (F1 and F2) with high specificity - 100% and 93.5% respectively. CONCLUSION: The use of the UEL allows the diagnosis of fibrosis in chronic liver diseases of different etiologies as an alternative to needle biopsy of the liver.

[Liver cirrhosis of alcoholic etiology complicated by the spontaneous bacterial peritonitis].

The case of spontaneous bacterial peritonitis (SBP) in the patient, with alcoholic cirrhosis, is presented in the article. Clinical observation demonstrates diagnostic hardships of latent clinical course of alcoholic cirrhosis, complicated SBP. Clinical observation demonstrated diagnostic consequence of ultrasound elastometry.

[Effect of zinc deficiency on effectiveness of the treatment of liver encephalopathy in patients with liver cirrhoses].

Zinc plays an important role in human physiologic processes being cofactor of many enzymes, it participates in numerous enzyme reactions. We have investigated 15 patients with liver cirrhoses of different etiology. With the rising of class of liver impairment and developing liver encephalopathy, level of zinc in blood drops. Treatment with diuretic therapy results in increase of discharge of zinc with urine and prevents recovery of its level in blood.