RU2414895C2 - Method of treating liver affection in leprosy patients - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to leprology, and can be applied for etiopathogenetic treatment of liver affection in leprosy patients. For this purpose simultaneously with specific anti-leprous therapy introduced is hepatoprotector heptral (S-adenozyle-L-methyonine). Specific anti-leprous therapy includes course introduction of dapson in dose 100 mg daily and riphampicine in dose 600 mg 1 time per month during 6 months with following interval in 1 month. Heptral is introduced in dose 400 mg twice per day in the morning and at lunch time perorally during two weeks.

EFFECT: claimed combined simultaneous introduction of medications in said regimen provides etiotropic and pathogenetic impact on disease, making it possible to realise correction of functional liver malfunctions, as well as to provide adequate protection from action of damaging factors.

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Description

The invention relates to the field of medicine, namely leprology, and can be, in particular, used to treat liver damage in patients with leprosy.

From the practice of medicine, a method is known for the treatment of liver damage in patients with leprosy, which consists in the use of methyluracil in combination with antipruritic drugs (Evstratova V.A. Non-specific agents (pyrogenal, gamma globulin, methyluracil) in the complex treatment of patients with leprosy / V.A. Evstratova, K.I. Nazarov, N.M. Goloshchapov, T.P. Poloz // Methodical recommendations. - Astrakhan, 1974. - 8 pp.). However, the disadvantage of this method is its low efficiency, because despite the relatively wide spectrum of action, the drug has a weakly expressed and insufficiently specific effect on pathological processes that occur, in particular, in the liver tissue. In addition, this method involves the long-term use of the drug courses throughout the entire period of anti-leprosy therapy.

There is also a method of treating liver damage in patients with leprosy, which consists in the use of the drug Liv 52 for leprous hepatitis (Nigam P. Leprous hepatitis: clinico-pathological study and therapeutic efficacy of Liv 52 / P. Nigam, SG Dayal, BMGoyal, KVNimkhedakar, LD Joshi, KCSamuel // Lepr. India. - 1978. - Vol.50, N 2. - P.185-195). The disadvantage of this method is that the drug in the known method contains a number of medicinal plants, each of which has a specific effect and in the aggregate determines the therapeutic effect. In this regard, on the one hand, it is not possible to conduct pharmacokinetic studies, and on the other hand, it is difficult to predict the individual body reaction to each component and the whole drug as a whole. This fact is of particular importance in old and old age due to a decrease in the reserve and adaptive capacity of the body, as well as a slowdown in the metabolic rate. In addition, in this age group, as a rule, several drugs are used in connection with a combined multiple organ pathology, the interaction with which a known drug is not described and is difficult to predict.

These shortcomings do not make it possible to obtain a specific technical result — an increase in the efficiency of the method.

The closest way to the proposed one is a method of treating liver damage in patients with leprosy, which consists in using any of the following drugs: campolone, lipocaine, nicotinic acid, insulin, glucose, vitamin B ₁₂ - in patients with leprosy with hepatitis on the background of specific therapy with sulfonic drugs (Evstratova V.A. Early diagnosis and outpatient treatment of patients with leprosy / V.A. Evstratova, K.I. Nazarov // Methodical letter. - Astrakhan, 1965. - 15 p.).

The similarity of this method with the proposed one lies in the fact that they both relate to leprology and consist in the combined use of specific anti-leprosy therapy with hepatoprotective.

The known method has the following disadvantages:

- low efficiency due to a nonspecific and weakly expressed effect on the morphofunctional state of the liver;

- lack of information on the influence of the known method on indicators of protein and lipid metabolism;

- lack of information about the influence of the known method on complications from the peripheral nervous system;

- lack of specific regimens for taking drugs.

These shortcomings do not make it possible to obtain a specific technical result - increasing the efficiency of the method.

Leprosy is a chronic infectious granulomatous disease caused by M. leprae, characterized by a long incubation period, prolonged course, a variety of clinical manifestations, a tendency to periodic exacerbations, affecting mainly the skin, mucous membranes of the upper respiratory tract, peripheral nervous system, musculoskeletal system and internal musculoskeletal system organs. Of the latter, the liver is most often affected, in which chronic leprosy hepatitis usually develops, confirmed by clinical and laboratory-instrumental examination methods. Impaired liver function in patients with lepromatous type of leprosy is expressed in the deviation of protein, pigment, enzyme, carbohydrate metabolism, as well as in a violation of the antitoxic function of the liver. The leprosy process causes quite pronounced specific and nonspecific changes in the parenchyma and stroma of the organ. In the etiology of liver damage during leprosy, it is impossible to exclude the toxic component due to the long-term use of drugs for both specific anti-leprosy therapy and the treatment of concomitant pathology. In this regard, the pharmacological protection of the liver from the action of damaging factors and the correction of morphofunctional disorders is an urgent problem not only in hepatology, but also in wide clinical practice as a whole, since the function of this organ suffers both with its isolated lesion and with a number of conditions and diseases characterized by multiple organ pathology. In particular, adequate hepatoprotection is one of the components of rational pharmacotherapy of a disease such as leprosy.

The drugs that have a selective effect on the morphofunctional state of the liver, increase its resistance to pathogenic effects, and also help restore its functions in various injuries, include hepatoprotectors, including substances of various chemical structures with a multidirectional mechanism of action. Among the variety of modern hepatoprotective agents, heptral was of interest, the active ingredient of which is S-adenosyl-L-methionine (ademethionine), a physiological substrate of many biological reactions, endogenously synthesized from methionine and adenosine and present in all tissues and body fluids. Ademethionine is a universal substrate of central importance in the reactions of transmethylation, trans sulfation and aminopropylation. The drug has pronounced anti-cholestatic, detoxifying, regenerating, antioxidant, anti-fibrosing properties. In addition, its neuroprotective and antidepressant effects have been established. Heptral has a quick positive effect on cognitive disorders, normalizes sleep, and also improves cerebral blood flow. In addition, the drug increases the synthesis of proteoglycans and leads to partial regeneration of cartilage. The results of the multiple effects of heptral on metabolism were the basis for its use to protect the liver from hepatotoxic substances, alcohol, medicines and infectious agents, as well as to correct existing morphofunctional disorders.

The present invention solves the main task of improving the efficiency of the method. The invention is expressed by a combination of essential features sufficient for the technical result provided by the invention.

The proposed method consists in the fact that in complex treatment at the same time as specific anti-leprosy therapy, including the course use of dapsone at a dose of 100 mg daily and rifampicin at a dose of 600 mg 1 time per month for 6 months, followed by a break of 1 month, heptral is used (S -adenosyl-L-methionine) at a dose of 400 mg twice daily in the morning and at lunchtime orally for two weeks.

The proposed method is as follows. A retrospective analysis of the case histories of patients on inpatient and outpatient care was performed for the period from 2003 to 2007. A group of 10 male patients with a diagnosed lepromatous type of leprosy was selected, during which period clinical, biochemical and ultrasound signs of liver damage of mixed etiology (specific, toxic, viral) were noted. In addition, all patients had signs of chronic specific polyneuropathy, and some had discirculatory encephalopathy of varying severity. Before and after prescribing the drug, clinical and laboratory-instrumental examination of patients was performed, including a biochemical blood test and ultrasound examination of the abdominal organs. Patients received specific anti-leprosy therapy, including the course use of dapsone at a dose of 100 mg daily and rifampicin at a dose of 600 mg once a month for 6 months, followed by a break of 1 month. Heptral was taken by patients at 400 mg (1 capsule) 2 times a day (morning and lunch) after meals, without chewing, for 2 weeks. Taking the drug in the morning is due to the existing tonic effect. The degree of changes in patient complaints from the hepatobiliary and nervous systems, the dynamics of laboratory parameters (total protein, albumin, urea, creatinine, residual nitrogen, total and conjugated bilirubin, thymol test, ALT, ACT, cholesterol, high density lipoproteins (HDL), triglycerides were evaluated ) and ultrasound of the liver. The safety of the drug was determined on the basis of data on possible adverse events, as well as on the basis of assessing changes in laboratory parameters. After taking the drug, a clinical effect was observed in all patients: improvement in general condition and well-being, weakening of the feeling of heaviness and discomfort in the liver area. In addition, the part showed a decrease in pain and stiffness in the joints of the upper extremities, a decrease in dizziness and increased stability during walking, which may be due to the neuroprotective effect of heptral. Positive dynamics was also noted according to clinical examination: in most patients, liver pain on palpation disappeared, there was a slight decrease in organ size. As a result of the analysis of the data of laboratory research methods, normalization of protein metabolism (a decrease to the norm of total protein with a constant level of albumin), a decrease in cholesterol and an increase in the concentration of high density lipoproteins were revealed.

The proposed method is achieved in comparison with the prototype to increase the effectiveness of the treatment of liver damage in patients with leprosy.

The proposed method was successfully tested in the clinic of the Federal State Institution “Research Institute for the Study of Leprosy of Roszdrav” for 10 patients during 2007-2008. Below are the results of testing.

Example 1

Patient M., born in 1936 Case history No. 3118.

DS: Leprosy, undifferentiated type, stage of regression. Chronic specific polyneuropathy with sensitive, motor, amyotrophic disorders, residual stage. Chronic osteomyelitis of the hands and feet. Chronic trophic ulcers of the hands and feet. Discirculatory encephalopathy of the II degree of mixed origin.

06/02/2008 Complaints of weakness, dizziness, periodic pain and a feeling of heaviness in the right hypochondrium, aches in the lower extremities. Objectively: the condition is satisfactory. The skin is free from manifestations of the leprosy process. In the lungs, vesicular breathing, no wheezing. NPV 16 in 1 minute. Heart sounds are muffled, the rhythm of cardiac activity is correct. PS 72 in 1 minute. HELL 125/75 mm Hg The abdomen is soft, painful in the right hypochondrium. The liver protrudes 1-1.5 cm from under the edge of the costal arch, painful on palpation, the edge is elastic. The spleen is not palpable. Blood stock from 2.06.2008: total protein 108.7 g / l, albumin 41.3 g / l, cholesterol 4.76 mmol / l; HDL 0.29 mmol / L. Ultrasound of the abdominal cavity from May 29, 2008. Liver: the left lobe is enlarged 9.1 × 7.7 cm (n <10.0 × 6.0 cm), the right lobe is not enlarged 13.0 × 11.5 cm (N <15 × 12.5 cm). The structure is diffuse-heterogeneous, the contours are even, echogenicity is normal. In the left lobe there are 2 anechogenic formations with an echogenic septum 1.4 × 0.9 cm and 0.7 × 0.8 cm; in the right lobe 2.8 × 2.6 cm - 7-8 seg. The pancreas is enlarged: head 3.2 cm (N up to 3.0 cm), body 2.3 cm (N up to 2.0 cm), tail 3.4 cm (N up to 2.8 cm). The contours are uneven, the structure is diffusely heterogeneous, echogenicity is increased. Conclusion: signs of chronic pancreatitis. Spleen without features. From 02.06.2008, the next course of anti-relapse therapy with 2 drugs was started: rifampicin at a dose of 600 mg once a month and dapsone at a dose of 100 mg daily for 6 months.

From May 28, 2008, heptral therapy was prescribed at a dose of 400 mg twice a day (morning, lunch) per os after meals for 2 weeks. Against the background of the therapy, the patient noted an improvement in overall health, a significant reduction in dizziness, the disappearance of pain and a feeling of heaviness in the right hypochondrium. Stiffness and aches in the lower extremities also decreased. When examined on June 16, 2008, the liver protrudes 0.5-1.0 cm from under the edge of the costal arch, the edge is elastic, painless on palpation. B / x blood from 06/16/2008: total protein 87.9 g / l, albumin 44.4 g / l, cholesterol 3.62 mmol / l; HDL 1.38 mmol / L. Ultrasound of the abdominal organs from 08/13/2008 Liver: the left lobe is not enlarged 9.2 × 6.0 cm (N <10.0 × 6.0 cm), the right lobe is not enlarged 13.0 × 11.0 cm ( N <15 × 12.5 cm). The contours are even, echogenicity is normal. In the left lobe there are 2 anechogenic formations of 1.4 × 0.9 cm and 0.7 × 0.8 cm; in the right lobe 2.8 × 2.7 cm. Ultrasound control after 6 months. Gall bladder without features. The pancreas is not enlarged, the structure is diffuse-heterogeneous, echogenicity is normal. Spleen without features.

Based on the above example, we can conclude that the use of heptral in complex treatment simultaneously with specific antileprosy therapy in leprosy patients is effective in improving clinical (from the hepatobiliary and nervous systems), biochemical parameters and results of ultrasound examination, providing adequate correction of polyetiological morphofunctional disorders and while protecting the liver from damaging factors, one of which is the long-term antimycobacterial therapy with sulfonic drugs, ultimately contributing to an improvement in the quality of life of patients with leprosy. This allows us to recommend heptral for use as a pathogenetically substantiated component of the complex therapy of this disease.

Example 2

Patient K., b. 1945 Case history No. 3876.

DS: Leprosy, lepromatous (LLp) type, stage of regression.

Chronic specific polyneuropathy with sensitive, motor, trophic disorders without exacerbation.

Chronic osteomyelitis of the bones of the left foot. Secondary renal amyloidosis. II degree dyscirculatory encephalopathy with vestibular syndrome.

On March 5, 2007, the next course of anti-relapse therapy with 2 drugs was started: rifampicin at a dose of 600 mg once a month and dapsone at a dose of 100 mg daily for 6 months.

At the time of the examination, May 22, 2007 he complained of periodic aching pains in the right hypochondrium, especially intensifying after eating fatty foods, weakness, fatigue. Objectively: the condition is satisfactory. The skin is free from manifestations of the leprosy process. In the lungs, vesicular breathing, no wheezing. NPV 17 in 1 minute. Heart sounds are muffled, the rhythm of cardiac activity is correct. PS 76 in 1 minute. HELL 130/80 mm Hg The abdomen is soft, palpation sensitive in the right hypochondrium. The liver protrudes 1.5-2.0 cm from under the edge of the costal arch, sensitive to palpation, the edge is elastic, mobile. The spleen is not palpable.

B / x blood from 05/21/2007: total protein 89.0 g / l, albumin 46.0 g / l, cholesterol 5.14 mmol / l; HDL 0.3 mmol / L. Ultrasound of the abdominal organs from 05.21.2007. Liver: the left lobe is enlarged 9.5 × 7.8 cm (N <10.0 × 6.0 cm), the right lobe is not enlarged 13.8 × 12.4 cm (N <15 × 12.5 cm). The contours are even, the structure is diffuse-heterogeneous, echogenicity is increased. Gall bladder without features. The pancreas is not enlarged, the contours are even, the structure is diffuse-heterogeneous, echogenicity is increased. Spleen: not enlarged - 9.8 × 4.6 cm (N 12.0 × 6.0 cm), smooth contours, diffuse-heterogeneous structure, increased echogenicity.

Starting May 22, 2007, heptral therapy was prescribed at a dose of 400 mg twice a day (morning, lunch) per os after meals for 2 weeks.

Against the background of the therapy, the patient noted an improvement in well-being, he has no complaints from the hepatobiliary system. On examination June 18, 2007, the liver protrudes 1.0 cm from under the edge of the costal arch, the edge is elastic, painless on palpation. B / x blood from 06/18/2007: total protein 81.3 g / l, albumin 63.8 g / l, cholesterol 3.23 mmol / l; HDL 1.27 mmol / L. Ultrasound of the abdominal cavity from 06/13/2007. Liver - without dynamics. Gall bladder - without features. The pancreas is not enlarged, the structure is homogeneous, echogenicity is normal. The spleen is not enlarged, the structure is homogeneous, echogenicity is normal.

Conclusion: the use of heptral in complex treatment simultaneously with specific anti-leprosy therapy in patients with leprosy is effective in improving clinical (from the hepatobiliary and nervous systems), biochemical parameters and results of ultrasound examination, providing adequate correction of polyetiological morphofunctional disorders and at the same time protecting the liver from damaging factors, one of which is long-term antimycobacterial therapy with sulfonic drugs, ultimately helping to improve the quality of life of patients with leprosy. This allows us to recommend heptral for use as a pathogenetically substantiated component of the complex therapy of this disease.

Example 3

Patient B., born in 1929 Case history No. 1664.

DS: Leprosy, lepromatous (LLs) type, regression stage. Chronic specific polyneuritis. Chronic osteomyelitis Chronic hepatitis Chronic cholecystopancreatitis. Discirculatory encephalopathy of the II-III degree of mixed origin (toxic-hypoxic, vascular).

Examined on May 22, 2007. Complaints of periodic aching pain in the right hypochondrium, heartburn, periodic weakness, increased fatigue, difficulty in movement in the joints of the upper extremities. Objectively: the condition is satisfactory. The skin is free from manifestations of the leprosy process. In the lungs, vesicular breathing, no wheezing. NPV 16 in 1 minute. Heart sounds are muffled, the rhythm of cardiac activity is correct. PS 74 in 1 minute. HELL 140/80 mm Hg The abdomen on palpation is soft, painless. The liver protrudes 1.0 cm from the edge of the costal arch, painless. The spleen is not palpable. Blood stock dated 05/21/2007: total protein 90.7 g / l, albumin 44.0 g / l, cholesterol 5.44 mmol / l; HDL 0.32 mmol / L. Ultrasound of the abdominal organs from 02.04.2007. The liver is not enlarged, the structure is diffuse-heterogeneous, echogenicity is moderately increased. Gall bladder without features. The pancreas is not enlarged, the contours are even, the structure is homogeneous, echogenicity is moderately increased. Spleen without features.

In a specific anti-leprosy treatment, a break between courses.

Starting May 22, 2007, heptral therapy was prescribed at a dose of 400 mg twice a day (morning, lunch) per os after meals for 2 weeks.

After the course of heptral therapy, the patient noted improvement in well-being, improved mobility in the joints of the upper extremities, pain in the right hypochondrium and dyspeptic symptoms. The objective status is the same. B / x blood from 06/06/2007: total protein 67.0 g / l, albumin 44.6 g / l, cholesterol 4.32 mmol / l; HDL 1.74 mmol / L. Ultrasound of the abdominal cavity from 06/13/2007: in comparison with the ultrasound picture from 04/02/2007, the echogenicity of the liver decreased slightly.

Conclusion: the use of heptral in complex treatment simultaneously with specific anti-leprosy therapy in patients with leprosy is effective in improving clinical (from the hepatobiliary and nervous systems), biochemical parameters and results of ultrasound examination, providing adequate correction of polyetiological morphofunctional disorders and at the same time protecting the liver from damaging factors, one of which is long-term antimycobacterial therapy with sulfonic drugs, ultimately helping to improve the quality of life of patients with leprosy. This allows us to recommend heptral for use as a pathogenetically substantiated component of the complex therapy of this disease.

Example 4

Patient G., born 1939 Case history No. 3854.

DS: Leprosy, lepromatous type, regression stage. Chronic specific polyneuropathy with sensitive, motor, trophic disorders without exacerbation. Discirculatory encephalopathy of the II-III degree of mixed origin. Chronic trophic foot ulcers.

Examined on May 22, 2007. Complaints of dizziness, instability when walking, periodic weakness, pain and difficulty in movement in the joints of the upper extremities. Objectively: the condition is satisfactory. The skin is free from manifestations of the leprosy process. In the lungs, vesicular breathing, no wheezing. NPV 17 in 1 minute. Heart sounds are muffled, the rhythm of cardiac activity is correct. PS 84 in 1 minute. HELL 140/85 mm Hg The abdomen on palpation is soft, participates in the act of breathing, painless. The liver protrudes 3.0-3.5 cm from under the edge of the costal arch, a dense texture, painless. The spleen is not palpable. Blood stock dated 05/21/2007: total protein 109.7 g / l, albumin 44.0 g / l, cholesterol 4.49 mmol / l; HDL 0.25 mmol / L. Ultrasound of the abdominal organs from 05.21.2007. Liver: left lobe 10 × 6.4 cm (N <10.0 × 6.0 cm), the right lobe is not enlarged; the structure is diffuse-heterogeneous, echogenicity is increased. The gall bladder is not enlarged, the wall is thickened to 0.5 cm (N to 0.4 cm), the contents are uniform, stones are not located. The pancreas is not enlarged, the contours are even, the structure is homogeneous, echogenicity is increased. Spleen without features.

In a specific anti-leprosy treatment, a break between courses. Starting May 22, 2007, heptral therapy was prescribed at a dose of 400 mg twice a day (morning, lunch) per os after meals for 2 weeks.

After a course of heptral therapy, the patient noted improvement in well-being, reduction of pain and improved mobility in the joints of the upper extremities. In addition, dizziness decreased significantly, and walking stability increased. On examination 4.06.2007, the liver protrudes 2.5-3.0 cm from under the edge of the costal arch, painless on palpation. Blood stock dated 06/06/2007: total protein 68.1 g / l, albumin 46.5 g / l, cholesterol 3.53 mmol / l; HDL 1.27 mmol / L. Ultrasound of the abdominal cavity from 06/14/2007 Liver: left lobe 9.6 × 6.9 cm (N <10.0 × 6.0 cm), right lobe 14.7 × 13.2 cm (N <15 × 12.5 cm), the structure is diffusely heterogeneous, echogenicity is increased. The gall bladder is not enlarged, the wall is not thickened, the contents are homogeneous, stones are not located. The pancreas is not enlarged, the contours are even, the structure is homogeneous, echogenicity is normal. The spleen is without features.

Conclusion: the use of heptral in complex treatment simultaneously with specific anti-leprosy therapy in patients with leprosy is effective in improving clinical (from the hepatobiliary and nervous systems), biochemical parameters and results of ultrasound examination, providing adequate correction of polyetiological morphofunctional disorders and at the same time protecting the liver from damaging factors, one of which is long-term antimycobacterial therapy with sulfonic drugs, ultimately helping to improve the quality of life of patients with leprosy. This allows us to recommend heptral for use as a pathogenetically substantiated component of the complex therapy of this disease.

The proposed method is achieved in comparison with the prototype to increase the effectiveness of the treatment of liver damage in patients with leprosy. The use of heptral in complex treatment simultaneously with anti-leprosy therapy has a pronounced specific effect on the clinical picture of the disease and the functional state of the liver, which consists in normalizing indicators of protein and lipid metabolism: reducing the total protein to normal with an unchanged level of albumin, lowering cholesterol and increasing the concentration of high density lipoproteins . In addition, in some cases, there is a positive dynamics from the side of the liver morphology - a decrease in organ size according to examination and ultrasound examination. The use of heptral in combination with specific anti-leprosy therapy also has a positive effect on the severity of the asthenoneurotic syndrome, provides a significant reduction in complaints from the peripheral nervous system (pain, paresthesia, numbness of the extremities, difficulty in moving joints). It should also be noted the convenience of the drug regimen, the presence of liquid and solid dosage forms and the short duration of the course of treatment.

The proposed method can be recommended for use in anti-leprosy and dermatovenereological institutions.

Claims (1)

A method of treating liver damage in patients with leprosy, which consists in combining the use of specific anti-leprosy therapy with hepatoprotective, characterized in that in complex treatment simultaneously with specific anti-leprosy therapy, which includes the course use of dapsone at a dose of 100 mg daily and rifampicin at a dose of 600 mg once a month for 6 months, followed by a break of 1 month, heptral (S-adenosyl-L-methionine) is used in a dose of 400 mg twice daily in the morning and at lunchtime orally for two weeks.