UA139440U - METHOD OF CORRECTION OF HYPERHOMOCYSTEMINEMIA IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE AND CHRONIC KIDNEY DISEASE - Google Patents

Abstract

A method of correcting hyperhomocysteinemia in patients with nonalcoholic fatty liver disease and chronic kidney disease by prescribing a combination of neurorubin-forte lactab 1 tablet per day and folic acid at a dose of 1 mg 1 time per day for three months. Additionally, the sublingual form of the drug agepta - S-adenosylmethionine in a dose of 400 mg 2 times a day for 30 days before obtaining a clinical effect.

Description

The useful model belongs to the field of medicine, namely internal medicine and gastroenterology, and can be applied to correct hyperhomocysteinemia in patients with non-alcoholic fatty liver disease and chronic kidney disease.

An important problem of internal medicine is the problem of comorbidity of nonalcoholic fatty liver disease (NAFLD) with obesity and chronic kidney disease (CKD), which has significant general medical and social significance (V.T. Ivashkin, 2016; Yu.M. Stepanov, 2014).

The range of diseases included in the concept of NAFLD includes non-alcoholic steatosis of the liver (NASP), steatohepatitis (NASH), which can be accompanied by liver fibrosis (FP) and transform into liver cirrhosis (CP) (G.D. Fadeenko, 2018; N.V Kharchenko, 2016).

The prevalence of NAFLD in the population is 10-33 95 (N.V. Kharchenko, G.A. Anokhina, 2011).

The development of NAFLD in obese patients is caused by a number of proven factors: insulin resistance, chronic postprandial hyperglycemia, glucose toxicity, glycosylation of structural and transport proteins, hyperlipidemia, dyslipidemia, hepatotoxicity of hypolipidemic agents (O. Ya. Babak, E. A. Lapshina, 2016; S. M. Tkach, T.L.

Cheverda, 2016) and a number of not yet established factors, the study of which is very relevant.

According to the literature, hyperhomocysteinemia (HC) is accompanied by damage to the endothelium of blood vessels, which is catalyzed by HC, the strengthening of atherogenesis processes with the deposition of subendothelially oxidized low-density lipoproteins. The final result of the effect of HC on the endothelium is the formation of atherosclerotic plaques. Homocysteine stimulates DNA synthesis in the cells of non-striated vascular muscles, induces their proliferation and the formation of a multi-layered cellular cuff around the perimeter of the vessels, which react twice or three times more strongly to the action of vasoconstrictors, disrupting organ blood circulation. HC also promotes an increase in the content of glycosaminoglycans in the intima of vessels, hyperproduction of extracellular matrix elements, sclerosing, strengthening of calcification, which leads to a decrease in their permeability, induction of the aggregation ability of platelets, and the formation of wall thrombi. Hyperhomocysteinemia can contribute to neovascularization of de Pomo angiogenesis, the formation of abnormal blood vessels that are more sensitive to the effects of vasoconstrictors. Due to the multifactorial, heterogeneous nature of non-alcoholic fatty liver disease, therapeutic approaches should also be complex.

Analogous to the useful model is a method of correcting hyperhomocysteinemia in patients with non-alcoholic fatty liver disease (Method of correction of hyperhomocysteinemia in patients with non-alcoholic fatty liver disease: pat. 120386 Ukraine. Mo 201705274; application 29.05.2017; publ. 25.10.2017, bull.

Mo 20), in which a combination of pharmacological agents is prescribed for patients depending on their genetic polymorphism, which is determined by polymerase chain reaction (PCR),

C5, why do they perform molecular genetic testing of the DNA of patients with the establishment of genetic variants of the polymorphic gene of methylenetetrahydrofolate reductase (MTGFR) and prescribe folic acid in the form of tablets in a dose of 1 mg per day for a month, and as vitamins of group B they use vitamin B12 in the form of intramuscular injections injections at a dose of 200 μg according to the scheme: the first two weeks - every day, the next two weeks - three times a week also for a month, while if after a month the patients do not have a positive effect from the treatment, patients with the 76771 polymorphism of the MTHGFR gene are given therapy continue for at least three months.

The disadvantages of the analogue method are that when using the specified method, the achievement of a stable remission of non-alcoholic steatohepatitis (NASH) is not noted, and at the same time, the stabilization of liver fibrosis is achieved only in half of patients with NASH, which can contribute to the further progression of NASH to liver cirrhosis.

The closest analogue of a useful model is the method of treating hyperhomocysteinemia (Method of correction of hyperhomocysteinemia: pat. 83970 Ukraine. Mo ts201303459; application. 03.21.2013; publ. 10.10.2013, bull. Mo 19), in which pharmacological agents are prescribed in a combination of neurorubin-forte lactab 1 tablet per day and folic acid at a dose of 1 mg once a day for three months.

The disadvantages of the closest analog-method are that this treatment regimen includes the use of B vitamins and folic acid, which can provoke the development of undesirable side effects, as well as the correction of hyperhomocysteinemia in patients with cardiovascular diseases, regardless of the functional state of the liver and the genotype of the patients .

The basis of the useful model is the task of improving the method of correction of hyperhomocysteinemia in patients with non-alcoholic fatty liver disease and chronic kidney disease by adding to the combination of drugs Neurorubin-forte lactab 1 tablet per day and folic acid at a dose of 1 mg 1 time per day for three months of appointment accept

(5-adenosylmethionine) in a dose of 400 mg 2 times a day for 30 days before obtaining a clinical effect.

Common features of the useful model and the closest analogue are the appointment of a combination of Neurorubin-forte lactab 1 tablet per day and folic acid at a dose of 1 mg 1 time per day for three months.

Distinctive features of the useful model from the closest analogue are that the sublingual form of the drug Agepta (5-adenosylmethionine) is additionally prescribed at a dose of 400 mg 2 times a day for 30 days until the clinical effect is obtained.

Definition of terms used in the description of the useful model: hyperhomocysteinemia, non-alcoholic fatty liver disease, chronic kidney disease, neurorubin-forte lactab, folic acid, agepta 5-adenosylmethionine.

Theoretical prerequisites for the implementation of a useful model.

Non-alcoholic fatty liver disease (NAFLD) is an independent liver disease characterized by histological, sonographic and other signs of fatty liver.

Chronic kidney disease is a disease that is characterized by long-term (at least 3 months) structural and/or functional renal changes according to clinical, laboratory, instrumental, and morphological studies, which at the same time give grounds for excluding the acute nature of the pathological process in the kidneys.

Agepta (5-adenosylmethionine) is a natural amino acid that is present in almost all tissues and liquid environments of the body. Ademethionine, first of all, acts as a coenzyme and metal group donor in many transmethylation reactions, which is an important metabolic process in humans and animals. Ademethionine is able to penetrate through the blood-brain barrier. High concentrations of ademetionine affect transmethylation processes, which are very important in brain tissue, due to the effect on the metabolism of catecholamines (dopamine, epinephrine, norepinephrine), indoleamines (serotonin, melatonin) and histamine. Ademethionine is a precursor in the formation of physiological sulfur compounds (cysteine, taurine, glutathione, coenzyme A, etc.) in transsulfuration reactions. Glutathione, the most powerful antioxidant, is an important component of the second phase of liver detoxification. Ademethionine increases the level of glutathione in patients with liver damage of both alcoholic and non-alcoholic origin.

A useful model is implemented as follows.

A patient with non-alcoholic fatty liver disease and chronic kidney disease is prescribed a combination of Neurorubin-forte lactab 1 tablet per day and folic acid at a dose of 1 mg once a day for three months with the addition of Agept (5-adenosylmethionine) at a dose of 400 mg 2 times a day until obtaining a clinical effect.

An example of using a useful model.

Patient V., 45 years old. Diagnosis: non-alcoholic fatty liver disease. CHN 18: chronic pyelonephritis, remission phase. Obesity II degree. She complained of discomfort in the right subcostal region, nausea, decreased appetite, general weakness, and rapid fatigue.

He has been sick for 5 years. She was periodically treated at her place of residence. The patient underwent a series of examinations, which included clinical blood and urine tests, biochemical tests (total bilirubin, conjugated and unconjugated bilirubin content, thymol test, proteinogram, coagulogram, blood lipid spectrum, blood amylase activity, electrolytes, enzyme activity: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AL), γ-glutamyltransferase (γ-GT), blood urea, creatinine. A comprehensive ultrasound examination (US) was performed on an ultrasound scanner "AO-4 Idea" (Vioteadisa , Italy).The stage of liver tissue fibrosis was studied using the FibrotTest, the degree of fatty liver dystrophy was studied using the SteatotTest (Viorgedissime, France).

The content of homocysteine in the blood (Achiz-Zpivia, OK) was determined by the enzyme-linked immunosorbent assay (ELISA).

Objective examination data: the general condition of the patient is conditionally satisfactory. Consciousness is clear.

The position in bed is active. The skin is pale, inelastic, without rashes, dry. Mucous membranes are pale pink in color, without rashes and hemorrhages. Both halves of the chest take equal part in the act of breathing. The frequency of respiratory movements is 18 per minute. Vesicular breathing is heard over the lungs, side breath sounds are not heard.

The area of the heart has not changed, the pulsation of the vessels of the neck is noticeable, the jugular veins are not swollen in a sitting position. The tones of the heart are clear, rhythmic. The vascular bundle does not extend beyond the sternum. Heart rate (HR) - 72/min, pulse rhythmic, of satisfactory properties, blood pressure - 120/80 mm. mercury Art. The abdomen is soft on palpation, sensitive in the right hypochondrium. The liver is 43 cm from the edge of the costal arch. The edge is rounded, sensitive to palpation. Ultrasound examination of abdominal organs. The liver was examined completely from the right hypochondrium, in the supine position. Dimensions: left lobe: anterior-posterior - 83 mm (enlarged), vertical 94 mm

(enlarged); tail lobe: thickness 33 mm (enlarged); right lobe: front-back - 132 mm, vertical - 178 mm (enlarged). The contour of the liver is even, indistinct, the lower edge is rounded, the capsule is not changed. The echo structure of the parenchyma of increased echogenicity with an indistinct granular pattern is heterogeneous. The sound conductivity of the tissue is significantly reduced (dorsal attenuation of the ultrasound signal). The vascular pattern is impoverished. For further examination of the liver, the following studies were performed: glycosylated Hb (NBAIss) - 7.8 90; viral hepatitis B and C markers are negative; degree of saturation of transferrin with iron (diagnosis of hemochromatosis) - 28 Fo.

A study of the homocysteine content in the blood of patient V. was conducted: the content of HC in the blood was 42.82 μmol/l.

In this regard, treatment was prescribed according to the proposed method.

30 days after the treatment, the following data were obtained: the content of HC in the blood was 35.21 μmol/l, which indicates a decrease in the risk of atherogenesis and the threat of a decrease in the functional state of the endothelium.

Therefore, the proposed method of correction of hyperhomocysteinemia in patients with non-alcoholic fatty liver disease and chronic kidney disease contributes to the elimination of signs of exacerbation of clinical syndromes of this pathology, correction of the main clinical and biochemical syndromes of the underlying disease, rapid reduction of the degree of hepatocyte steatosis, inhibition of fibrosis of liver tissue and improvement of hepatic blood circulation.

Technical result. The proposed method makes it possible to effectively correct hyperhomocysteinemia in patients with non-alcoholic fatty liver disease and chronic kidney disease by using the sublingual form of agept (5-adenosylmethionine) as an antioxidant, membrane stabilizer and hepatoprotector, which inhibits the progression of liver fibrosis in the presence of comorbidities.

Claims (1)

USEFUL MODEL FORMULA The method of correcting hyperhomocysteinemia in patients with non-alcoholic fatty liver disease and chronic kidney disease by prescribing a combination of Neurorubin-forte lactab 1 tablet per day and folic acid at a dose of 1 mg 1 time per day for three months, which Zo differs in that the sublingual form of the drug Agepta - 5-adenosylmethionine is additionally prescribed at a dose of 400 mg 2 times a day for 30 days until the clinical effect is obtained.