UA120696U - METHOD OF TREATMENT OF PATIENTS WITH EXTRACTION OF CHRONIC ALCOHOLIC HEPATITIS - Google Patents

Abstract

The method of treatment of patients with exacerbation of chronic alcoholic hepatitis, in which the introduction of drugs with hepatoprotective and detoxifying activity is performed, additionally administered immunoactive drug polyoxidonium. Polioxidonium is administered intramuscularly according to the scheme: 6 mg 1 time per day for 3-5 days in a row, then 6 mg every other day for 5-7 injections of the drug, depending on the effect achieved.

Description

A useful model belongs to the field of medicine, namely hepatology and narcology, and can be used to treat patients with exacerbation of chronic alcoholic hepatitis.

The relevance of the subject of a useful model is related to the widespread alcoholism of the population in modern conditions, the frequent formation in the presence of chronic alcohol intoxication of liver pathology of alcoholic genesis, which requires further development of rational methods of treatment of this pathology.

A known method of treating patients with an exacerbation of chronic alcoholic hepatitis (CALH), which includes administering to them a drug with hepatoprotective and detoxifying activity - sodium nucleate 0.5 g 3-4 times a day internally for 15-20 days in a row |Frolov V.M.

Alcoholic hepatopathy and its modern treatment / V.M. Frolov. - In the book: Alcoholic liver disease: Sat. science works - Kharkiv: Khmy, 1993. - P. 223-228).

However, clinical experience indicates insufficient immunomodulatory activity of sodium nucleicate, especially in the presence of a clearly expressed autoimmune component. In addition, in recent years, this drug is practically absent in the pharmacy network of Ukraine, which does not allow the use of this method in wide medical practice.

There is a way to treat patients with exacerbation of CAlH by administering hepatoprotectors to them, namely silibor and essentiale (Podmova S.D. Liver diseases (a guide for doctors). - 3rd ed. - M.: Medicine, 1998. - P. 278- 285).

But this method is not effective enough and causes a positive effect only in 60-65 95 patients with CAlH.

There is also a known method of treatment of patients with an exacerbation of CAlH, which includes additional intramuscular administration of a drug with hepatoprotective and detoxifying activity - splenin (Pat. Mo 52291 A, Ukraine, MPK AB6IK 35/28. / Frolov V.M., Teryoshin V.O. ., Shapovalov

K.A., Pchelintsiv A.V. - 3. Mo 2002042659, Application 04/03/2002, Publ. 16.12.2002, Bull. Mo 12.

Method of treatment of exacerbations of chronic alcoholic hepatitis).

The disadvantage of the method is that this combination of drugs does not provide a sufficient hepatoprotective effect, especially during exacerbations of CAlH. In addition, splenin is currently practically absent in the pharmacy network of Ukraine, which makes it impossible to use this method in wide medical practice.

Zo There is also a method of treating patients with an exacerbation of CAlH, which includes the administration of sodium nucleate, splenin, and additionally - drugs with an antioxidant effect in medium therapeutic doses for 10-15 days in a row (Pat. Mo 58341 A, Ukraine, MPK Ab61K 31/355, AYEAK 31/ 375. / Frolov

V.M., Pustovy Y.G., Shapovalov K.A., Teryoshin V.A., Volman O0.V.-3. MO 2002119469, Application 28.11.2002, Publ. 15.07.2003, Bull. Mo 7. Method of treatment of chronic alcoholic hepatitis in the acute phase).

However, when using this method in patients with CAlH in the phase of exacerbation of the pathological process in the liver, full clinical remission is not achieved and some biochemical parameters, namely functional tests of the liver, are not normalized.

There is also a known method of treating patients with an exacerbation of CAlH by administering a drug with hepatoprotective and detoxifying activity of glutargin in the form of 4 96 solution of 20-30 ml intravenously twice a day for 5-7 days in a row and then, after improving the functional state of the liver and reducing the phenomena of "metabolic " toxicosis, 0.5 g (2 tablets) inside for another 15-20 days in a row (Pat. Mo 69733 A, Ukraine, MPK AbIK 31/195. / Frolov V.M.,

Teryoshin V.O., Shapovalov K.A. - 3. Mo 20031110685, Application 26.11.2003, Publ. 15.09.2004, Bull. Mo 9. Method of treatment of patients with exacerbation of chronic alcoholic hepatitis).

This method of treating patients with an exacerbation of CAlH is the closest to what is claimed, in terms of technical essence and the result that can be achieved, therefore it was chosen as a prototype.

Among the shortcomings of the prototype is the fact that in a number of patients with the presence of CAlH, significant shifts in some biochemical and immunological parameters are noted, that is, the presence of secondary immunodeficiency.

The purpose of the useful model is to increase the effectiveness of the known method of treating patients with an exacerbation of chronic hepatitis C, to accelerate the achievement of stable clinical and biochemical remission and the normalization of immunological indicators.

The task is solved by additional appointment for patients with exacerbation

CAlLH of the modern immunoactive drug polyoxidonium (PO).

PO is a high-molecular physiologically active compound that exhibits pronounced immunotropic activity. It has been established that PO has a positive effect on all aspects of the body's defense against foreign agents of an antigenic nature, increasing the decreased and decreasing the increased indicators of immunity, that is, it is a true immunomodulator. The targets for the pharmacological action of PO are cells of the phagocytic system and natural killers, i.e. MK cells. PO exerts a stimulating effect on the production of a number of cytokines by macrophage-monocyte cells, in particular II - 18, IS-6, TMEsa and α-interferon. In case of insufficient humoral immunity, PO also significantly increases antibody formation. In addition to the immunomodulatory effect, PO is also characterized by the presence of detoxifying, antioxidant and membrane-stabilizing activity, which makes it an effective drug in the complex treatment of acute and chronic infections of any etiology. PO is registered in Ukraine as a medicinal product (registration certificate Mo

OA/ZZ 44/02/01) and approved for clinical use by the Order of the Ministry of Health of Ukraine dated January 26, 2015.

The technical efficiency of the claimed method is based on the principle established for the first time in the experiment and then confirmed in the clinic, that PO shows a clearly expressed positive effect in the case of liver damage by ethanol, including in the presence of cholestatic syndrome in patients, which is often registered in patients with CAlLH, which is important for clinical practice. Previously, PO in a complex with glutargin was not used in patients with an exacerbation of CAlH.

The claimed method is carried out as follows. A patient with an exacerbation of CAlH is prescribed as a drug with hepatoprotective and detoxifying activity glutargin in the form of 4 95 solution of 20-30 ml intravenously twice a day for 5-7 days, then 0.5 g (2 tablets) internally for another 15-20 days in a row and additionally - immunoactive drug PO intramuscularly according to the scheme: 6 mg once a day for 3-5 days in a row, then 6 mg every other day for another 5-7 injections of the drug.

In order to confirm the effectiveness of the claimed method, 131 patients with an exacerbation of HCAI were examined. All patients under observation were divided into two groups (primary and comparison), which were randomized according to age, sex, and severity of clinical manifestations of CAlH, as well as the total duration of the disease. The main group (73 people) was treated according to the declared method, the comparison group (58 people) was treated according to the prototype.

Clinically, before the start of treatment, all the examined were in the exacerbation phase of CAlH. The clinical manifestations of the disease were characterized by the presence of general weakness, malaise, irritability, headache, decreased appetite, sleep disturbances, heaviness in the right hypochondrium, itching of the skin, nausea, sensitivity of the liver to palpation, hepatomegaly, subicteric sclera and skin, significant coating of the tongue with a white coating and darkening of the urine. In a number of cases, a dull pain in the epigastrium was noted, which was a sign of sunburn or concomitant damage to the stomach, in some cases - the presence of moderately pronounced jaundice.

The examination of the patients was carried out dynamically, it included general clinical and general laboratory methods, ultrasound examination (ultrasound) of the abdominal organs, biochemical methods of studying functional tests of the liver (bilirubin, activity of serum aminotransferases - alanine aminotransferase (ALT) and aspartate aminotransferase (AST), concentration of circulating immune complexes (CIC ) and their most toxic molecular weight fraction (115-195), as well as the value of the thymol test).

It was established that the use of PO in the treatment of patients with an exacerbation of CAlH led to a significant improvement in their clinical condition in comparison with patients of the comparison group (Table 1).

Table 1

The influence of the declared and known methods of treatment of patients with an exacerbation of CAlH on clinical indicators (Mat)

We are located at Pio NIS p-7Z p-58

Continuation of table 1

The influence of the declared and known methods of treatment of patients with an exacerbation of CAlH on clinical indicators (Mat)

Clinical signs Main group Comparison group n-7Z n-58 9,850.8 16,050.8 11,020.9 23 subicteric sclera and skin 9,620.6 16,250.7 9,250.5 18,751.0 6,820.4 12,520.4

Note: in the table 1-3, the P indicator is calculated between the indicators of the main group and the comparison group.

A reduction in the duration of clinical manifestations of the disease was noted - general weakness (on average by 2.1250.3 days), malaise (by 5.750.2 days), irritability (by 5.0-0.3 days), headache (by 5, 4:20.4 days), decreased appetite (by 4.8:20.2 days), sleep disturbances (by 5.9240.3 days), heaviness in the right hypochondrium (by 7.320.4 days), skin itching (for 7.60.4 days), nausea (for 4.9:0.5 days), sensitivity of the liver during palpation (for 6.220.3 days), hepatomegaly (for 12.4:20.7 days), subicteric sclera and skin (for 6.6:0.4 days), significant coating of the tongue with plaque (for 9.5:20.7 days) and darkening of urine (for 5,720.4 days). Full clinical remission of CAlH was achieved in the main group by 13.4:30.6 days from the start of treatment, in the comparison group - by 25.7 0.9 days, i.e. 1.92 times later. Therefore, under the influence of the claimed method, the achievement of clinical remission in patients with an exacerbation of CAlLH was accelerated.

The positive effect of the declared method of treating patients with exacerbations was also noted

ChAlLH on biochemical indicators. Before the start of treatment, biochemical changes in both groups were of the same type. They were characterized by a moderate increase in the level of total and direct bilirubin, the activity of serum aminotransferases - ALT and AST, and the value of the thymol test. Repeated biochemical examination after treatment made it possible to establish that in the main group of patients a clearly expressed positive dynamics of biochemical indicators was noted (Table 2).

Table 2

The influence of the declared and known methods of treatment of patients with an exacerbation of CAlH on biochemical indicators (Mat)

Biochemical parameters Norm Main group Comparison group n-7Z n-58

Bilirubin (μmolllii | 0001000 405 39.7k0.67 »0y 12.0-20.0 19.750.5 29.8:50.47 «0.01 26.00, 25.20. 5 201 2.t9jo 2.950, 27 201

AlAT (mmol/g-l) 0.35-0.68 0.7140.07 1.59-0.087: 3.160 where 3.220 201

AsAT (mmol/g-l) 0.28-0.55 0.8140.057 1.9750.067 147-044 13.90 201

Thymol test (OD) of the VZHY century

Notes: in tables 2 and 3, the numerator indicates the indicators before the start of treatment, the denominator - after its completion; the probability of discrepancies relative to the corresponding indicators of the norm "- at

Р«0.05, и - Р«е001, их - рР«0.001.

Thus, in the main group of patients, the content of total bilirubin, the activity of ALT and the value of the thymol test practically normalized, and the level of direct bilirubin and the activity of AST decreased significantly. In the comparison group, the positive dynamics of biochemical indicators was less pronounced. In this contingent, the level of total and direct bilirubin, the activity of ALT and ASAT, as well as the indicator of thymol test remained above normal.

Thus, the obtained data testify to the effectiveness of the declared method of treatment of patients with an exacerbation of CAlH, which led to the acceleration of the clinical and biochemical remission of hepatitis.

In addition, it was established that the use of the claimed method significantly improves the immunological parameters of the subjects. So, before the start of treatment, both groups of patients had the same type of changes on the part of the latter, which were characterized by T-lymphopenia, a decrease in the number of circulating T-helpers (2047) and the immunoregulatory index СО4/С08, an increase in the level

thyroid gland, mainly due to their average molecular fraction (Table 3).

Table C

The influence of the declared and known methods of treatment of patients with exacerbation of CAlH on immunological indicators (Mat) zennnnnny by her | ZNeKya | action co p-7Z p-58 and 5241 and 51.71 201 and 36.3-1.67 35.68--1.577 201 and 21.68521.1 22.15-1.2 201 1.67-0, 0577 1.6220.04 201 430-015 4.2450.13y 201 2.26vzh0 11 dag1v0 1 201

Re-examination of patients made it possible to establish that in the main group there was a clear positive dynamic of immunological indicators. After completion of the treatment, normalization of the number of SOC: cells (T-lymphocytes), СО4--lymphocytes (T-helpers) and the immunoregulatory index СО4/СО8 was noted, as well as a significant decrease in the level of CYCs and their most pathogenic medium molecular fraction. So, in the main group of patients, along with the normalization of clinical and biochemical indicators, a clear positive trend in immunological tests was also established.

In the comparison group, the positive dynamics of the studied tests was significantly lower, significant shifts in immunological indicators were noted, that is, the presence of secondary immunodeficiency.

Thus, the declared method of treatment of patients with an exacerbation of CAlH determines the acceleration of the achievement of stable clinical and biochemical remission and the normalization of immunological indicators. Dispensary examination made it possible to establish that the average duration of remission achieved in the main group was 9.7 0.5 months, while in the comparison group it was only 6.1:0.4 months, i.e. 1.59 times less (P«e0, 01). This makes it possible to consider the use of the declared method of treatment of such patients in the conditions of gastroenterology and narcology departments as appropriate.

We give specific examples of the use of the claimed method.

Example 1. Patient S., 41 years old, has been under dispensary supervision for the past 4 years with a diagnosis of CAlH. Exacerbation of the pathological process on the part of the liver is noted 2-3 times

Z for a year, the last one started Z days ago after abusing alcoholic beverages. He complains of general weakness, malaise, headache, heaviness in the epigastrium and right hypochondrium, lack of appetite, nausea, irritability, restless sleep, itching of the skin of the trunk and limbs, darkening of urine. On examination: the general condition of the patient is moderately severe, the sclera is moderately icteric, the skin is subicteric. Abdominal palpation is sensitive in the epigastrium and right hypochondrium, the liver protrudes 3-4 cm from the edge of the costal arch, its edge is sensitive to palpation. The tongue is heavily coated with a dirty whitish coating. Urine when examined is dark yellow. General blood test:

Er.-4.0410'2/l, Hb-130 g/l, L - 6.4-109/l., e-3, n - 4, c - 66, l - 24, m - 3; ESR - 12 mm/h. Urine analysis - presence of bilirubin and urobilin. Biochemical blood analysis: total bilirubin - 40.1 μmol/l, direct - 25.3 μmol/l, AlAT - 2.67 mmol/h.-l, ASAT - 2.98 mmol/h.-l, thymol test - 14.2 units Ultrasound: the liver is enlarged, the echogenicity is uneven, with small areas of increased echogenic density. Clinical diagnosis: chronic alcoholic hepatitis in the acute phase, moderately severe course.

The patient was prescribed treatment according to the stated method - glutargin 20 ml 4 95 solution intravenously twice a day for 5 days in a row, then 0.5 g (2 tablets) internally for another 15 days in a row and additionally - PO intramuscularly 6 mg 1 once a day for 3 days in a row, then 6 mg every other day for 5 more injections of the drug.

Under the influence of the treatment, the patient's nausea and sleep disturbances disappeared on the 3rd day, headache and decreased appetite - on the 4th day; general weakness, malaise and irritability - on the 5th day, darkening of urine - on the b day, heaviness in the right hypochondrium - on the 8th day, sensitivity of the liver during palpation, subicteric sclera and skin, coating of the tongue with a dirty white coating - on the 9th day, skin itching and hepatomegaly - on the 10th day. The patient's well-being and general condition completely normalized within two weeks. When re-examining the biochemical indicators on the 15th day after the start of treatment, the following results were obtained: total bilirubin - 19.4 μmol/l, direct - 3.9 μmol/l, ALT - 0.69 mmol/h.-l, AST - 0.76 mmol/h.-l, thymol test - 5.6 units. Thus, clinical and biochemical remission of hepatitis was achieved by the 15th day after the start of treatment.

Conducting an immunological examination made it possible to establish that before the start of treatment, the immunogram was characterized by the presence of T-lymphopenia (53 95), a decrease in T-helpers (37 90) and the immunoregulatory index (1.76), an increase in the level of TsiIK (4.19 g/l) and of their average molecular fraction (2.12 g/l). After the patient was treated according to the stated method, a repeated immunological examination allowed establishing an increase in the number of - T-lymphocytes to 71 95 and the subpopulation of T-helpers to 47 95, the CO4/C08 ratio - to 2.04, a decrease in the CIC level to 2.14 g/l and the average molecular fraction of immune complexes - up to 1.34 g/l. Thus, almost complete normalization of the patient's immunological indicators was noted. Dispensary supervision for 1 year made it possible to establish the duration of achieved clinical and biochemical remission of hepatitis. The general condition of the patient during this period was satisfactory, there were no exacerbations of the pathological process.

Example 2. Patient M., 47 years old, has been under dispensary supervision for the past 9 years with a diagnosis of chronic alcoholism and alcoholic hepatitis. Exacerbations of hepatitis are noted 3-4 times a year. The last exacerbation occurred 2 days ago after abusing alcoholic beverages. The patient complains of general weakness, malaise, headache, dizziness, lack of appetite, nausea, heaviness in the epigastrium and right hypochondrium, sleep disturbance, bitterness in the mouth, irritability, itching of the skin of the trunk and limbs, darkening of urine.

On examination: the general condition of the patient is moderately severe, the sclera is moderately icteric, the skin is subicteric. Pulse - 86 bpm, rhythmic, of satisfactory quality. AT-135/80 mm Hg. Art. Hard breathing in the lungs, scattered dry wheezes. Heart - tones are rhythmic, moderately muffled. Abdominal palpation is sensitive in the epigastrium and right hypochondrium. The liver protrudes 4-5 cm below the edge of the costal arch, its edge is sensitive to palpation. The tongue is thickly coated with a dirty white coating.

Urine when examined is dark yellow. General blood analysis: Er.-4.04-10'2/l, Hb-120 g/l, L - 6.1-109/l, e- 1, p-6, c - 68, l - 23, m - 2; ESR - 14 mm/h. Urine analysis revealed the presence of bilirubin and urobilin. Biochemical blood analysis: total bilirubin - 42.1 μmol/l, direct - 27.2 μmol/l,

AlAT - 2.83 mmol/h.-l, ASAT - 3.28 mmol/h.-l, thymol test - 15 units. Ultrasound: enlargement of the liver and unevenness of its echo density. Clinical diagnosis: chronic alcoholic hepatitis in the acute phase, moderately severe course. The patient was prescribed treatment according to the stated method - glutargin 30 ml of 4 95 solution intravenously twice a day for 7 days in a row, and then 0.5 g (2 tablets) inside for another 20 days in a row and additionally - PO intramuscularly 6 mg 1 time a day for 5 days in a row, then 6 mg every other day for 7 more injections of the drug.

The dynamic examination made it possible to establish that, under the influence of the declared method of treatment, the patient's nausea and sleep disturbances disappeared on the 4th day, headache and decreased

Loss of appetite - on the 5th day, general weakness, malaise and irritability - on the 6th day, darkening of urine - on the 7th day, heaviness in the epigastrium and a bitter taste in the mouth - on the 9th day, sensitivity of the liver on palpation, jaundice of the sclera and subicteric skin, covering the tongue with a dirty white coating - on the 10th day, itching of the skin - on the 11th day, hepatomegaly - on the 12th day. In general, the general condition of the patient and his well-being normalized within 20 days from the start of treatment.

Upon repeated study of biochemical parameters, it was established that on the 19th day from the start of treatment, the level of total bilirubin (20.3 μmol/l), and its direct fraction (4.9 μmol/l), the activity of aminotransferases - AlAT (0.75 mmol/h-l) and AST (0.86 mmol/h-l), thymol test indicator (5.9 units). Therefore, by the 20th day from the start of treatment 60, a full-fledged clinical and biochemical remission was achieved.

Conducting an immunological examination of the patient made it possible to establish that before the start of treatment, in the period of exacerbation of HAl"H, the immunogram was characterized by the presence of T-lymphopenia (4995), a decrease in the number of T-helpers (35590) and the immunoregulatory index (1.61), an increase in the level of TsiIK ( 4.37 g/l) and fractions of medium molecular weight immune complexes (2.36 g/l).

After the patient was treated according to the stated method, a repeated immunological examination made it possible to establish a clear positive trend regarding the dynamics of immunological indicators. The number of T-lymphocytes increased to 69 95 and the subpopulation of T-helpers (СО04У) to 45 95, the value of the СО4/СО8 ratio increased to 1.94. The concentration of CIC decreased to 2.31 g/l, and the content of their average molecular fraction - to 1.47 g/l. Therefore, the patient has an almost complete normalization of immunological indicators.

Dispensary supervision for 1 year made it possible to establish the duration of achieved clinical and biochemical remission of hepatitis. The general condition of the patient and his well-being were satisfactory, during the entire period of dispensary supervision, there were no exacerbations of the pathological process in the liver.

Thus, the obtained data testify to the effectiveness of the claimed method of treatment of patients with exacerbation of HAlLIgH and its significant advantages over the prototype. The claimed method does not require the use of scarce and expensive drugs, does not cause adverse side effects, including allergic ones, and therefore can be recommended for widespread use in the conditions of therapeutic, gastroenterological and narcological departments.

Claims (2)

USEFUL MODEL FORMULA 1. The method of treating patients with an exacerbation of chronic alcoholic hepatitis, in which drugs 3 with hepatoprotective and detoxifying activity are administered, which is distinguished by the fact that the immunoactive drug polyoxidonium is additionally administered. 2. The method according to claim 1, which differs in that polyoxidonium is administered intramuscularly according to the scheme: 6 mg once a day for 3-5 days in a row, then 6 mg every other day for another 5-7 injections of the drug, in depending on the achieved effect. 000 KomputernaverstkaL.Tsikhanovska.d (00000000 Ministry of Economic Development and Trade of Ukraine, 12/2 M. Hrushevsky St., Kyiv, 01008, Ukraine SE "Ukrainian Institute of Intellectual Property", Glazunova St., 1, Kyiv - 42, 01601 (c;