Method for combination treatment of acute alcoholic hepatitis with organic selenitium and vitamin e

FIELD: medicine.

SUBSTANCE: integrated therapy additionally involves administering thin-walled Capsicum annuum powder of the type paprika in a dose of 30 g with the specified selenium contents of 1 mg/kg and a capsule of alpha-tocopherol acetate in a dose of 100 mg manufactured by Lyumi, LLC (Ekaterinburg) orally during meals 3 times a day. The length of the treatment is 20 days.

EFFECT: invention enables reducing the time of the treatment, increasing its efficacy, and prolonging remission.

1 tbl, 2 dwg, 2 ex


The invention relates to medicine, namely to Hepatology, and can be used in the treatment of alcoholic liver disease.

Alcohol abuse is considered the main aetiological factors of chronic liver disease in the world, including in Russia (Khazanov A. I., Vasiliev A. P., Pekhterev S. G. and other problems of etiological factors of liver cirrhosis in hospitalized patients (1992-2005): alcoholic cirrhosis comes out on top in number of patients and high mortality // Klin, gepatol. - 2006. - Vol. 2, No. 2. - P. 11-16). The relatively young age of those affected, their employment in socially useful work, prolonged hospital stay, the need for a long period of outpatient observation - all this makes the disease one of the most expensive in the clinic of internal diseases and shows significant damage alcoholic liver disease the industrial sector of the Russian Federation, as well as lack of effective therapy.

One of the ways-analogues for the treatment of acute alcoholic hepatitis is the use of corticosteroids (Chedid A., Mendenhall, C. L., Gartside P. Prognostic factors in alcoholic liver disease // Am. J. Gastroenterol. -2001. - Vol.12. - P. 23-29.). However, the disadvantage of this method is the limitation of its use in patients with severe alcoholic hepatitis for fear of infectious OS�of ogneni.

In recent times attempts have been made to evaluate the clinical effectiveness of the use of direct anti-cytokine drugs, particularly infliximab. However, the results of these studies do not allow one to evaluate the rationality of such approaches in the treatment of acute alcoholic hepatitis (Mureno G. N., Karlotti G., Giovani F. T. et al. Infliximab treatment among the patients with acute alcoholic hepatitis. A pilot study // Ital. J. Gastroenterol. Hepatol. - 2003. - Vol.10. - P. 24-29.).

Currently proven part of the processes of lipid peroxidation and selenium in the pathogenesis of acute alcoholic hepatitis (Rui M. Rua, M. L. Ojeda, F. Nogales et al. Serum selenium levels and oxidative balance as differential markers in hepatic damage caused by alcohol // Life Sciences, 17 January 2014, P. 158-163). Selenium is a structural component of the antioxidant enzyme glutathioneperoxidase. These provisions allow you to look at hepatocellular insufficiency decompensated hepatitis of alcoholic etiology as to the dynamic mismatch between the current needs of the organism in selenium and functionality of the liver, which appear in the indicators.

The method-analogue is the treatment of biologically active forms of inorganic selenium compounds containing Selenite or sodium selenate. However, Selenite and sodium selenate are not able to stock up in the body and should not be included in therapy inside�them diseases. In addition, if it is impossible to dispose of the excess selenide formed during the metabolism of these drugs, inorganic selenium can accumulate in the tissues of the body in the form of free hydrosilylation, which is extremely toxic.

Closest analogue is the prototype of the investigated method is the correction of selenium deficiency by taking in organic selenium in the form of BAD "Selenium-asset", "Antioxycaps with selenium" or in the form of hepatoprotective pharmaceutical composition patent for the invention of "hepatoprotective Pharmaceutical composition and method of treatment" No. 2391989 from 21.08.2008). However, the disadvantage taken with this method drugs is joint content of selenium per capsule vitamin C (ascorbic acid) and thioctic, greenexpo acids respectively, while the biologically active form of selenium is unstable and is rapidly reduced by the action of acids. Selenium should be taken separately with this group of chemicals, as they mutually inhibit the absorption of one another. In addition, there is a disadvantage that the drugs "Antioxycaps with selenium" and hepatoprotective pharmaceutical composition selenium dosage is below average for a healthy person is 30 mcg.

Organic animal form of selenium absorbed by 30%, n�organic form - 10% (Yu. V. Marushko, Ostapenko Y. Y. Role of selenium in clinical practice// children lcar - 2012. - No. 5. - P. 32-36). However, the most preferred for the body of a vegetative form of selenium because of its high digestibility (95-98%), therefore, most authors recommend this as the most preferred form in the body supplied with selenium. Therefore, the closest to the investigated method is the prototype of correction of selenium status by using powder of thin-walled sweet pepper varieties "lighthouse" tall paprika installed selenium 1 mg/kg in the dose of 50 g/d (application for the invention "Method of fotokorrektsii of selenium deficiency in humans" No. 2013138967/15 from 20.08.2013). The disadvantage of the claimed method is the daily dosage for an adult healthy person in terms of selenium is 50 ág/day, that does not account for the increased consumption of the trace element selenium in acute alcoholic hepatitis (L. A. Reshetnik, E. O. Lee, V. A. Rock. The daily requirement for selenium in healthy individuals // nutrition, 2000, vol. 47, No. 4, pp. 15-21). In addition to the above, selenium potentiates the antioxidant activity of vitamin E (tocopherol), activates glutathione together with vitamin E protects the cell membrane, mitochondria, microsomes and lysosomes from lipid peroxidation. On this basis, pathogenetically used�the use of selenium together with tocopherol, what is not in this version.

In the available literature, we have not met information about the combined use of selenium and tocopherol in the treatment of acute alcoholic hepatitis, their influence on the course of pathological process in the liver, and data routes of administration, dosages and regimens. Thus, the use of powder thin-walled sweet pepper varieties "lighthouse" tall paprika, enriched with selenium and tocopherol for the treatment of toxic liver diseases proposed by the authors for the first time.

The object of the invention is to improve the quality of complex therapy of alcoholic liver disease in the form of acute alcoholic hepatitis, devoid of the above drawbacks.

The technical result consists in the fact that the method of combined treatment of acute alcoholic hepatitis with organic selenium and vitamin E increases the duration of remission and helps to overcome the shortcomings of standard treatment regimens.

The technical result is achieved in that in the scheme of treatment along with standard integrated therapy (ursodeoxycholic acid 15 mg/kg/day orally, Essentiale N 5 ml/day intravenously) included a combination of two drugs: powder thin-walled sweet pepper varieties "lighthouse" tall paprika (Photo 1, Photo 2) installed selenium 1 mg/kg dozirovke 30 g per single dose and capsule, contains 100 mg of alpha-tocopherol acetate at one time the manufacturer LLC "Lumi" (Ekaterinburg). The introduction of both drugs is carried out orally during meal, 3 times a day, which provides the daily dose was reduced to 90 mcg selenium and 300 mg of alpha-tocopherol acetate. Course duration is 20 days. This pepper is grown with the use of NPK fertilizers of prolonged action Apionidae, containing 0.03% Na2SeO4(application for the invention "Method of enrichment of selenium pepper sweet paprika cultivar" No. 2012122267/13 dated 29.05.2012; Standard of Organization "Paprika, enriched with selenium. Industrial raw materials. Technological conditions" (one HUNDRED 45727225-37-2011) the Application to the application 1). The use of fertilizers of prolonged action APION, containing 0.03% Na2SeO4increases the accumulation of selenium in fruits 7.7 times, resulting in increased antioxidant activity of the powder, paprika 1.5 times compared with the control. Selenium in combination with tocopherol ensures optimal and sustained antioxidant protection, enhances the action of the main drugs.

The technical result was achieved in the treatment of 36 patients with an established diagnosis of acute alcoholic hepatitis of moderate severity". All cases were confirmed by clinical and laboratory methods. In the amount of complex therapy of 12 patients from gr�PPy 3 received powder thin-walled sweet pepper varieties "lighthouse" tall paprika installed selenium 1 mg/kg (powder paprika), a daily dose of 90 g of oral alpha-tocopherol acetate at a daily dose of 300 mg orally; 12 patients of group 2 received powder paprika in a daily dose of 50 g of oral. A comparison group consisted of 12 patients from group 1 who received only basic therapy. Dangerous side effects when using selenium at the dose of 50 μg, 90 μg and 200 mg of alpha-tocopherol acetate per day is not revealed. Statistical data processing was performed using Statistica v6.0 (StatSoft, USA).

The results of the study are shown in table 1, show that the duration of symptoms such as jaundice, itching, fever, abdominal pain compared groups differed significantly. The decrease in the concentration of total bilirubin, γ-glutamyl-transpeptidaza alkaline phosphatase of blood in the group treated with the drug selenium and tocopherol was significantly higher than in the 2nd and 1st teams. The level of selenium in blood serum in group 3 changed from mild forms of the disease (70-90 µg/l) until the optimal security of the body (116-130 µg/l). The inclusion of powder thin-walled sweet pepper varieties "lighthouse" tall paprika, enriched with selenium, and alpha-tocopherol acetate in the standard therapy helps to restore the processes of antioxidant protection in the form of decrease of glutathione peroxidase activity.

Length of bed-days in gr�PE patients receiving combined therapy with the powder paprika in a dose of 90 mcg/day and tocopherol, was significantly less than in the group of patients treated with powder paprika in a dose of 50 mg/day, and only the combined therapy.

The data obtained indicate that the proposed method has advantages in comparison with analogues:

- improves the clinical course of the disease;

- improves the bioavailability of selenium in the product;

- reduces the duration of hospital stay;

- improving the quality of life of patients;

- reduced diversion of patients from the performance of employment duties because of temporary disability;

- physiological method, chemically and psychologically safe for the patient;

- conducting the method does not require special knowledge among health care personnel.

The results of the research allowed us to make a number of promising conclusions about the advisability of further study and use of selenium in combination with vitamin E in the complex therapy of alcoholic liver disease.

Example 1.

Patient T., aged 58. In June 2013, hospitalized with complaints of yellowness of the skin, General weakness, swelling of feet observed for 1.5 months prior to admission. History of alcohol abuse for 7 years, daily doses when�imagelogo alcohol ranged from 200 to 300 ml in terms of 96% alcohol, before the advent of the above complaints drinking alcohol every day during the week. The Department conducted a complete laboratory and instrumental examination, and then diagnosed as acute alcoholic hepatitis of moderate severity, associated with liver cirrhosis grade C child-Pugh. The content of selenium in the serum of 56 ág/l (severe deficiency). Start therapy with 30 g of powder of thin-walled sweet pepper varieties "lighthouse" orally during meals 3 times a day, 100 mg of alpha-tocopherol acetate manufacturer LLC "Lumi" (Ekaterinburg) orally during meals 3 times a day, ursodeoxycholic acid 15 mg/kg/day orally, Essentiale N 5 ml/day intravenously, spironolactone 400 mg/day of oral and furosemide (100 mg/day intravenously; positive dynamics was observed: decreased pain in the abdomen, yellowness of the skin. After 20 days the drug of selenium and tocopherol have been completely eliminated, relapse was not observed. At follow-up after 32 days of clinical and laboratory remission, the level of selenium in serum 114 ág/l (suboptimal provision), the patient was discharged with a closed leaf of invalidity.

Example 2.

Patient E., 34 years. He considers himself a patient since April 18, 2013, when after a three-day alcohol use appeared �water, yellowness of the skin, pain in the epigastrium, was not treated. History of regular alcohol consumption is 12 years, daily doses taken alcohol ranged from 300 to 500 ml in terms of 96% alcohol. April 24, 2013 he began to notice the deterioration in the form of asthenic syndrome, turned to the physician and was referred to the hospital. After execution of laboratorial screening patient diagnosed with acute alcoholic hepatitis of moderate severity, associated with cirrhosis of the liver, In class on child-Pugh. The content of selenium in the serum of 93 ág/l (mild deficiency). Start therapy with 30 mg of powder of thin-walled sweet pepper varieties Mayak, orally during meals 3 times a day, 100 mg of alpha-tocopherol acetate manufacturer LLC "Lumi" (Ekaterinburg) orally during meals 3 times a day, ursodeoxycholic acid 15 mg/kg/day orally, Essentiale N 5 ml/day intravenously, positive dynamics was observed: decreased jaundice, pain in the abdomen. After 20 days the drug of selenium and tocopherol have been completely eliminated, relapse was not observed. At the control examination after 24 days of clinical and laboratory remission, the level of selenium in the serum of 129 ág/l (optimal security).

The method of combined treatment of acute alcoholic hepatitis with organic selenium and vitamin E, characterized in that in the active stage of the disease is taken orally during meal powder thin-walled sweet pepper varieties "lighthouse" tall paprika installed selenium 1 mg/kg alpha-tocopherol acetate manufacturer LLC "Lumi" (Ekaterinburg), respectively, at doses of 30 mg and 100 mg single dose, 3 times a day for 20 days, which allows for early clinical effect, to restore the antioxidant defense processes and improve the bioavailability of trace elements.


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