UA56508A - Method for treating acute conditions in chronic viral hepatitis c - Google Patents

Abstract

The method for treating the acute conditions in chronic viral hepatitis C comprises employing the interferon inducer – cycloferon. In addition alpha-interferon is injected intramuscularly thrice a day at a dose of 1 million units throughout the first week of the treatment, then twice or thrice a week at the same dose for 2-3 months depending on the effect obtained. Splenin is injected intramuscularly in a volume of 2 ml twice a day throughout first 10-15 days of the treatment, then at the same dose once a day for further 15-20 days. The silica enterosorbents are taken thrice a day between the meals and drug administration at a dose of 200-250 ml of 1-2% aqueous suspension for 10-12 days. The antioxidants (tocopherol acetate, ascorutin, quercetin) are also used at the average therapeutic doses for 20-30 days.

Description

Description of the invention

The invention relates to the field of medicine, namely to methods of treating infectious diseases. 2 The relevance of the problem is related to the significant prevalence of chronic viral hepatitis C (HCV) in modern conditions and the insufficient perfection of the existing methods of treating patients with this pathology, in connection with which further optimization of the methods of treatment of HCV is required.

There is a way to treat exacerbations of chronic hepatitis C by administering large doses of drugs / - interferon, such as intron A, reaferon, roferon, lapheron and others at 3ml OD 3 times a week for 6 months and more than 70 (Rissiotso A., Magadopa U., Mapye R. E.A. Ipiepegop ipegaru ip spgopis Peraiiv So // NeraiysIodu. - 1993. -

M.17. - R.359-363. However, the effectiveness of this method of treatment does not exceed ZO - 4095. In addition, long-term administration of alpha interferon drugs can contribute to the development of autoimmune reactions and other complications, which are noted in 25 - 3095 patients, and the number of which increases when interferons are prescribed for more than 3 months in a row 12 To increase the effectiveness of the treatment of exacerbations of chronic hepatitis C, it is suggested to use the introduction of antiviral drugs, mainly ribavirin, along with alpha interferon drugs (Oamiz o.I., Evierap

K., Kividi M.ea. Kesotrbripai ipiebegop aya - 25 ayupe og ip sotrepaiop m/y hiramihipy bog (eaitepi oi ipiepegop geiagze ip spgopis Peraiiv S o// Mem Epdiapa Mogpa! oi Meadisipe. - 1998. - M. 339. - R. 1493 - 1499). This method is more effective, helps to accelerate the achievement of remission by inhibiting the synthesis of 20 viral nucleic acids and reducing the number of viruses in the patient's body. However, ribavirin can cause the development of dyspeptic phenomena; its use is contraindicated in acute diseases of the liver and kidneys. In addition, it was found that administration of a combination of alpha-interferon and ribavirin to patients with exacerbation of HCV, along with increasing the effect of treatment, also causes a significant increase in the number of side effects, especially hemolysis of erythrocytes, which requires withdrawal of ribavirin. 25 There is also a known method of treating exacerbations of HCV with the help of inducers of interferon production, namely "cycloferon or isoprinosine (Andriychyk M.A., Gospodarskyi I.Ya., Zaigriychuk O.P. The use of inducers of interferon production in patients with hepatitis B and C // Virus'ne hepatitis ! with the parenteral mechanism of transmission of pathogens and their origin. - Kiev, 2001. - P. 232-234). This method provides a positive clinical effect and does not cause negative side reactions, so we chose it as a prototype. со 30 One of the shortcomings of the prototype is that only 5,095 examined patients had a positive effect. Therefore, it was necessary to further improve the existing method - the prototype.

The goal of the invention was to increase the effectiveness of treatment of exacerbations of HCV by additional administration of moderate doses of o-interferons in combination with splenin, enterosorbents and antioxidants. Gee)

The development of the proposed method of treatment of exacerbations of HCV is based on the first established by us in

From the experimental conditions and the regularity confirmed in the clinic, which consists in the fact that the joint administration of inducers of interferon production, primarily cycloferon. And o-interferons (laferon, reoferon, intron A, and others.) Causes mutual potentiation of the antiviral and immunomodulating effect of both drugs, and in clinical terms ensures the acceleration of the achievement of stable and long-term remission of HCV. The inclusion of splenin in the program for the treatment of HCV exacerbations is associated with the hepatoprotective effect of this drug in HCV patients, established by the authors of the application, as well as with the known detoxifying, immunomodulating and antiallergic effects of splenin. In addition, as a mandatory component of the general program for the treatment of exacerbations of HCV, we offer the introduction of modern domestic siliceous enterosorbents - enterosgel, polysorb, sylard

P, enterosorb and others. We found that the use of these enterosorbents as an additional component of the general program of treatment of HCV leads to the acceleration of the elimination of the syndrome of endogenous sl 15 "metabolic" intoxication, a decrease in the level of circulating immune complexes, as well as "medium molecules", and ensures the implementation of the immunomodulating effect of splenin, cycloferon and co-interferons (for example, (o) laferon) due to "opening" of surface receptors of immunocompetent cells, cleaning them from toxic sl molecules. 50 We have also established that the additional administration of a complex of antioxidants (tocopherol acetate, ascorutin, quercetin) to patients with an exacerbation of HCV contributes to the potentiation of the immunocorrective effect due to a decrease in the intensity of lipid peroxidation (LPO) and is therefore pathogenetically justified.

The proposed method is used as follows. When establishing a diagnosis of an exacerbation of HCV, which is documented by the presence of HCV RNA in the blood, an increase in the activity of serum aminotransferases - ALT and AST by 2 times or more, the presence of hepatomegaly and splenomegaly, jaundice, an increase in the level of bilirubin, especially the direct (linked) fraction , the patient is prescribed treatment according to the proposed method, namely cycloferon 2 ml of 12.595 solution once a day intramuscularly for 5 days in a row, then every other day 2 ml for another 5-10 infections, depending on the effect achieved. In addition, the introduction of a - interferon (Laferon, Reaferon, Intron A and others) is prescribed intramuscularly in millions of units 3 times a day for the first week of treatment, then in millions. OD 2 - S times a week for 2 - S months; splenin 2 ml 2 times a day intramuscularly during the first 10 - 15 days of treatment for another 15 - 20 days in a row and modern siliceous enterosorbents (enterosgel, sylard P, enterosorb and others) 200 - 250 ml 1 - 2965 water suspension inside three times a day between meals and medicines for 10 - 12 days in a row and antioxidants (tocopherol acetate, quercetin, askorutin) internally in medium therapeutic doses for 20 - 30 days in a row.

Depending on the achieved effect, the introduction of cycloferon, splenin and enterosorbents can be repeated 65 times, with an interval of 30-40 days, but our clinical experience shows that this is necessary only in individual cases of treatment, as a rule, in the presence of some unfavorable conditions - a significant duration of illness (more than 5 years), elderly age of patients, history of alcohol abuse and others.

When developing the proposed method of treatment for exacerbations of chronic hepatitis C, we examined 52 patients with this diagnosis who had clinical and laboratory signs of exacerbation of hepatitis, who made up the main group and received treatment according to the proposed method of treatment and ZO patients with the same diagnosis, who made up the comparison group , which was treated according to the prototype method. Age, gender composition and the total duration of the disease in both groups were typical.

A comparison of clinical, biochemical and immunological indicators was carried out in both groups during the course of 70 treatments, and then, after achieving stable remission, during dispensary supervision from 2 to 6 years in a row.

Conducting clinical supervision and laboratory examination made it possible to establish that the proposed method has significant advantages over the prototype method. and

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Table 1 shows data on the effect of the proposed method on clinical indicators in the patients examined by us in comparison with the prototype method. It can be seen from the table that the use of the proposed method for the treatment of exacerbations of chronic hepatitis C reduces the duration of jaundice by an average of 4.6 - 0.2 days, the darkening of urine - by 5.1 and 0.2 days, and the subicterity of the sclera - by 5.4 0.2 days, hepatomegaly - for 11.2 - 0.3 ise) days, splenomegaly - for 13.5 - 0.35 days, sensitivity of the edge of the liver during palpation - for 5.5 - 0.2 days (Р и « 0.01). yu

It is significant that relative to the group of patients with exacerbation of HCV, which was treated according to the prototype method, the duration of preservation of hepatomegaly was reduced by 1.8 times, splenomegaly by 2.25 times, sensitivity of the edge of the liver during palpation by 2.1 times.

Under the influence of the proposed method of treatment, in the main group that received treatment according to the method developed by us, the duration of general weakness was reduced by 10.3 vs. 0.4 days (2 times), the duration of illness was reduced by 9.5 vs. 0, 2 days (2 times), decreased appetite - for 8.3 - 0.2 days (2 times), heaviness in the right and hypochondrium - for 7.8 - 0.2 days (2.2 times ), reduction of working capacity - by 10.9 and 0.2 days (2.1 times). Therefore, "" the obtained data testify to the effectiveness of the proposed method of treatment of patients with an exacerbation of chronic hepatitis C, as it contributes to the acceleration of the elimination of clinical manifestations of exacerbation and the achievement of remission of hepatitis C.

The impact of the proposed method of treatment and the dynamics of biochemical indicators in patients with "sl exacerbation of HCV" were also studied. The obtained data are summarized in Table 2.

Table 2 shows that before the start of treatment, both groups of subjects had the same biochemical shifts

Me indicators, which were characterized by a moderate increase in the level of total bilirubin and the direct (related) "sl fraction, an increase in the activity of serum aminotransferases (AlAT and AsAT), as well as excretory enzymes - alkaline phosphatase (AL) and gammaglutamyl transpeptidase (GGTP), an increase in the indicator of thymol tests and a decrease in the albumin/globulin (A/G) ratio.

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NI AN writing on drinking VE 70 During the re-examination on the 30th day after the start of treatment, it was established that in the patients of the main group who received treatment according to the proposed method, the normalization of both the total level of bilirubin and the content of direct (related ) fraction, a decrease in serum aminotransferase activity - AlAT and AsAT, as well as the indicator of thymol test to the norm. The normalization of the activity of excretory enzymes - LF and GGTP and the A/G indicator was also noted. Thus, in the examined patients with an exacerbation of acute respiratory syndrome /5 within 1 month, a complete clinical and biochemical remission of the disease was achieved, which was evidenced by the normalization of clinical and biochemical indicators.

In the comparison group, which received treatment according to the existing method, positive dynamics of the studied biochemical indicators were also noted, but not so significant.

Re-examination made it possible to note that in the majority of patients of the compared group, which was treated with the help of the existing prototype method, the studied biochemical indicators slightly exceeded the upper limit of the norm, which indicated incomplete normalization of functional liver tests. A comprehensive assessment of the entire set of clinical and biochemical indicators made it possible to establish that within 71 months, a complete clinical and biochemical remission of HCV was achieved in 48 (92.3 and 4905) patients of the main group who received treatment according to the proposed method, and in 14 (46, 7 and 3.295) persons in the comparison group (Р « 0.01). Partial remission with improvement of clinical and laboratory indicators was noted in the last 4 (7.7 vs. 2,290) patients of the main group and in 10 (33.3 vs. 2,895) people from the comparison group. In 6 (20 out of 2,595) patients of the comparison group, when using the existing method - prototype, no significant positive changes in clinical and biochemical indicators were noted, that is, remission was not achieved at all, there was an exacerbation of the pathological process in the liver parenchyma, which required additional treatment measures. о о о The conducting of a dispensary examination for 2 years or more made it possible to establish the following. In the main group of 50 patients who were under supervision throughout this period, a full-fledged long-term clinical and biochemical remission with the absence of exacerbations for 2 years or more occurred in 47 (94 x 4,295) patients, in 3 patients (b x 195 ) the storage period of remission was from 7 to 12 months. In the comparison group of 24 patients, remission was achieved in 10 (41.7% - 3.690) for less than 6 months, and in b patients (25% 390) - from b to c 12 months. Complete remission lasting 2 years or more occurred only in 8 (33.3 vs. 3.495) persons of the comparison group, i.e. 2.8 times less compared to the total number of patients in the main group who achieved remission, or 3.4 times less compared to the total number of patients in both groups, since full remission lasting 2 years or more was achieved in 47 out of 52 patients in the main group (90.4 x 4.595) and 8 out of 30 in the comparison group (26.6 x 3.590). "

The conditional economic effect associated with the acceleration of the achievement of a stable long-term clinical and biochemical 2-second remission and, in connection with this, the increase in the working capacity of the patients, amounts to 526 hryvnias. per 1 patient.

So, the proposed method is useful, as it helps to accelerate the achievement of long-lasting clinical and biochemical remission during exacerbation of HCV. It is based on the use of domestic drugs, does not require scarce or very expensive drugs, and therefore can be recommended for widespread use in the conditions of infectious disease departments and hospitals in the treatment of exacerbations of HCV. c The given data can be supported by the following specific examples of using the proposed method. (22) Example 1. Patient S., 52 years old, an employee, has been suffering from HCV for the past 4 years, exacerbations are noted mainly 2 times a year. Previously, she received only pathogenetic therapy. She was examined for HCV during another exacerbation. She complained of general weakness, malaise, moderate headache, decreased appetite, heaviness in the right hypochondrium, significant decrease in work capacity, darkening of urine. On examination: the general condition of the patient is moderately severe, moderate scleral jaundice, subicteric skin is noted. The liver is enlarged, protrudes 4 cm from the right side, below the edge of the costal arch, the spleen is 1 - 2 cm in position on the right side. The edge of the liver is sensitive to palpation.

Laboratory examination: Er. - 3.92710 12/l, Hb - 142g/l, L. -5.17109/l, e. - 1, p. - 4, s - 52, l - 30, m - » 4; SHOE - bmm/h. Urine analysis - bile pigments, urobilin. Biochemical indicators: total bilirubin - 52.3μmol/l, direct - 29.1μmol/l, indirect - 23.2μmol/l; AlAT - 2.8bmmol/hl, AsAT - 2.23mmol/hl, thymol test - 8.2 units, GHTP - 312bnmol/l, LF - 4.9mmol/hl, A/ - 0.8. Diagnosis: Chronic viral hepatitis C in the exacerbation phase, moderately severe course, confirmed by the duration of the disease (about 4 years), the presence in the anamnesis of surgical intervention, blood transfusion and recurrent infections 5 years ago, the presence at the time of the examination of clinical symptoms of a general toxic and hepatic nature , an increase in the activity of aminotransferases and changes in other functional tests of the liver, as well as detection by the ELISA method in the blood of the sick patient - NSM Id (C - M), in the absence of markers of hepatitis A and B. 65 After clarifying the diagnosis, the patient was prescribed treatment according to the proposed method , which included the introduction of cycloferon in the form of a 12.595 solution of 2 ml once a day intramurally for 5 consecutive days, then 2 ml every other day for 5 more infections (a total of 20 ml of cycloferon per course), and additionally Laferon by Imln. IU three times a day the first week for another 2 months (in total for the course of treatment 21 million IU in 1 week, and 1 billion IU in the next 2 months, i.e. a total of 37 million IU laferon), splenin 2 ml 2 times a day) intravenously ulcer during the first 10 days of treatment, then 2 ml once a day for another 15 days (total of 7 Oml of splenin per course of treatment), silard P as a modern silica enterosorbent, 200 ml of 195 aqueous suspension C times a day between meals and medications for 10 days in a row and a complex of antioxidants inside - tocopherol acetate, askorutin and quercetin in medium therapeutic doses for 20 days in a row. 70 Under the influence, the general condition of the patient significantly improved. Jaundice of the sclera disappeared on the 5th day from the start of treatment, subicteric skin and sclera - on the 10th day, urine was light already on the 4th day of treatment.

General weakness and malaise disappeared on the 8th day from the start of treatment, appetite appeared on the seventh day, heaviness in the right hypochondrium disappeared on the sixth day. The sensitivity of the edge of the liver during palpation was eliminated on the fifth day, the size of the liver decreased on the 14th day from the start of treatment, the spleen - on the 10th day. On the 5th day, the patient's ability to work normalized.

A repeated biochemical examination on the 30th day after the start of treatment allowed establishing the normalization of biochemical indicators. Indeed, the level of total bilirubin decreased to 14.2 μmol/l, direct - to

Z,bmmol/l, ALT activity - up to 0.55 mmol/hl, AST - up to 0.41 mmol/hl, thymol test indicator - up to 4 4 units, GHTP activity - up to 2011 nmol/l, LF - up to 1.2 mmol/g "l. The A/G ratio increased to 1.1.

Thus, a complete clinical and biochemical remission of HCV was achieved in patient S. Dispensary supervision for 2 years made it possible to establish the duration of the achieved remission. There were no relapses or exacerbations of the disease during the entire period of dispensary examination, the patient's working capacity was preserved.

Example 2.

Patient K., 42 years old, an employee, has been suffering from chronic hepatitis C for 5 years, exacerbations of the pathological process are observed 1-2 times a year. Previously received only pathogenetic therapy. She was examined for another exacerbation of chronic hepatitis C. He complained of general weakness, malaise, headache, decreased appetite, darkening of "urine, moderate jaundice of the skin and sclera, reduced work capacity, heaviness in the right subcostal area. During the examination, the presence of moderate jaundice of the skin and sclera, hepatomegaly (3-4cm), splenomegaly (n2cm ), sensitivity of the edge of the liver during palpation, darkening of urine. During the biochemical examination, it was established the presence of hyperbilirubinemia (56.bmmol/l), an increase in the content of the direct (bound) bilirubin fraction (30.2mmol/l), the activity of AlAT (3.0bmmol/hl) and Asat (2.5bmmol /hl), GHTP (326Onmol/l) and LF (4.9mmol/hl), an increase in the thymol test index (8.10 units), and a decrease in the A/H ratio (0.81).

Diagnosis: Chronic viral hepatitis C in the exacerbation phase, moderately severe course, established on the basis of the disease duration (about 5 years), the presence in the anamnesis of blood transfusion and recurrent infections 6 years ago, the detection of a characteristic clinical and biochemical picture at the time of the examination, and also HCV markers in the patient's blood - apiia - NSM Id (SM) by the ELISA method in the absence of hepatitis A and B markers in the patient's blood.

After clarifying the diagnosis, the patient was prescribed treatment according to the proposed method, namely intramuscular administration of 12.595 cycloferon solution 2 ml once a day for 5 consecutive days, and then 2 ml every other day for another 10 infections, additionally administration of laferon according to Imln . OD With times a day, the first week - ptv) with treatment and then according to Tmln. OD With times a week for 1 month and 2 times a week for another 2 months; 2 ml of splenin 2 times a day intramuscularly during the first 15 days of treatment, then 2 ml 1 time a day for another 20 days;" in a row, enterosorbent - sylard P 250 ml of 295 aqueous suspension inside three times a day between meals and medicines for 12 days in a row and a complex of antioxidants inside (tocopherol acetate, quercetin, askorutin) in therapeutic doses for 30 days in a row. A total of ZOml cycloferon was administered during the course of treatment, with 49 mln. 1 unit of laferon, 100 Oml of splenin.

Under the influence of the treatment, the general condition of the patient and his well-being significantly improved.

Me, Jaundice disappeared on the sixth day from the start of treatment, subicteric sclera - on the tenth day, darkening of urine on the sixth day, general weakness and malaise - on the 10th day of treatment, heaviness in the right hypochondrium - on the 8th day. Hepatomegaly was eliminated on the 14th day of treatment, splenomegaly on the 10th day, decreased work capacity on the 10th day. c When the biochemical parameters were re-examined on the 30th day from the beginning of the treatment, clearly expressed positive dynamics were established. The level of total bilirubin decreased to 16.8 μmol/l, direct -to

Z.bmmol/l, ALT activity - up to 0.62mmol/hl, AsAT - up to 042mmol/hl, thymol test - up to 4.80d., GGTP activity - up to 1986Onmol/l, LF - up to 1.1mmol/g"l The AUT ratio increased to 1.08.

Therefore, a complete clinical and biochemical remission of HCV was achieved in patient K. Dispensary supervision

R for 2 years allowed to establish the duration of the achieved remission. There were no relapses and exacerbations of the disease during the entire period of dispensary examination, the patient's working capacity was preserved.

Thus, the proposed method has significant advantages over the existing one and can be recommended for widespread use in the practice of infectious diseases departments and hospitals.

Claims (1)

The formula of the invention 65 The method of treatment of exacerbations of chronic viral hepatitis C, which includes the administration of the cycloferon interferonogenesis inducer to the patient, which is distinguished by the fact that 1 million units of o-interferon are additionally administered intramuscularly once a day for the first week of treatment, then 1 million units 2-3 times a week for 2-3 months in a row, depending on the effect achieved; splenin 2 ml 2 times a day intramuscularly during the first 10-15 days of treatment, then 2 ml 1 time a day for another 15-20 days; silica enterosorbents inside 200-250 ml of 1-295 water suspension three times a day between meals and medicines for 10-12 days and antioxidants (tocopherol acetate, ascorutin, quercetin) inside in medium therapeutic doses for 20-30 days. Official bulletin "Industrial Property". Book 1 "Inventions, useful models, topographies of integrated microcircuits", 2003, M 5, 15.05.2003. State Department of Intellectual Property of the Ministry of Education and Science of Ukraine. « c «c) IS) (Se) IS c) - with . and? 1 (22) 1 o 50 IR e) 60 b5