RU2180599C2 - Method for treating the chronic viral hepatitis c patients having hepatic hemosiderosis - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves applying 3-5 sessions of cytopheresis by taking 800.0-1000.0 ml of blood, centrifuging it at 2000 rpm speed during 1 h with following 350-500 ml of blood cells being separated and returning 450-500 ml of separated autoplasma to the patient after 3-4 days long pause. Then α₂-interferon is administered. EFFECT: enhanced effectiveness of treatment; simultaneous removal of excessive iron and hepatitis C virus from the liver. 2 tbl

Description

 The invention relates to medicine, in particular for the treatment of patients with chronic hepatitis C with hemosiderosis of the liver.

 A known method of treating patients with chronic viral hepatitis C with hemosiderosis of the liver ribavirin. The drug is prescribed orally for 6 months with a constant increase in dose from 600 to 1200 mg / day. Ribavirin is an antiviral drug of the group of abnormal nucleosides of a virologostatic effect, effective in infections caused by RNA viruses. When taking ribavirin, side effects are possible - abdominal discomfort, hemolytic anemia. However, in half of the patients, after discontinuation of the drug, the initial level of AlAT is restored. Ribavirin does not affect the level of HCV-PHK in the blood (Di Bisceglic AM, Hepatitis C and hepatocellular carcinoma // Semin. Liver Dis., 1995., V.330, p. 137-138; Hoofnagle JH, Di Bisceglic AM The treatment of chronic viral hepatitis // N. Engl. J. Med, 1997, V.336, 5, p. 347-356).

 A known method of treating patients with chronic viral hepatitis C with hemosiderosis of the liver with ursodeoxycholic acid. It was found that ursodeoxycholic acid in patients with chronic viral hepatitis C improves the well-being of patients, reduces jaundice, contributes to the positive dynamics of biochemical parameters, in particular, a decrease in the activity of AlAT. However, the drug does not affect the content of HCV-PHK in the blood, on the morphological picture of liver tissue (Sorinson S. N. Viral hepatitis., St. Petersburg. TEZA., 1997, 306 p.).

 A known method of treating patients with chronic viral hepatitis C with hemosiderosis of the liver by the inducer of interferon - cycloferon. The drug causes the formation of α-, β-, γ-interferons in the body by leukocytes, macrophages, fibroblasts, epithelial cells, has an immunomodulating effect. In the treatment of patients with chronic viral hepatitis C, cycloferon is used in a dose of 2 mg on the 1st, 2nd, 4th, 6th, 8th, 10th and 12th day of the course of therapy. However, the drug does not affect cholestatic and mesenchymal-inflammatory syndromes. After treatment with cycloferon, 40% of patients again show signs of activity of the pathological process (Okorokov A.N. Treatment of diseases of internal organs, vol. 1, 1997, Mn. Vim. School, 533 p .; Romantsov MG, Ershov F.I. ., Kovalenko A. L., Golubev S.Yu. “Immunodeficiency states: correction with cycloferon.” PTFF Polisan S.Peterburg, 1998, 113 pp.).

 A known method of treating patients with chronic viral hepatitis C with hemosiderosis of the liver roncoleukin (recombinant human interleukin-2). The drug plays a key role in the process of initiation and development of the immune response, stimulates the proliferation of T-lymphocytes, activating them, as a result of which they become cytotoxic killer cells. Roncoleukin normalizes biochemical indicators of activity, indicators of peripheral blood. At the same time, according to PCR, virus C elimination is observed only in 40% of the tested (Zhurkin A.T., Firsov S.L., Khomchenko I.V. application ". St. Petersburg, 1999, S. 9-15).

 As a prototype for the closest technical essence, we have chosen a method for the treatment of patients with chronic viral hepatitis C with hemosiderosis of the liver with alpha-interferon. Typically, alpha-interferon is administered at 3 million ME 3 times a week subcutaneously or intramuscularly for 6-12 months. When using the drug, there is a decrease in HCV, normalization of biochemical signs of activity. The frequency of a positive response to treatment is 40-50%. However, in 50% of patients who responded positively to interferon therapy, relapse develops after treatment is discontinued and the overall level of sustained response is only 25%. The lack of efficacy of alpha-interferon in many respects prevents its widespread use in the treatment of chronic viral hepatitis C (Arber N., Moshkowitz M, Konikoff F., et al. High level serum iron suppose weak respose to interferon treatment in patients with chronic HCV infection. // Dig. Dis. Sci., 1995, V.40, 12, p. 2431-2433; Girelli CM, Mirata C., Lesinigo C, Casiraghi A. Iron overload and response to alpha-interferon in chronic hepatitis C. / / Amer. J. Gastroeter., 1995, V.90, 1, p. 170-171).

 The objective of the invention is to develop a method of treatment that increases the effectiveness of therapy of alpha-interferon by first removing high iron content from the liver.

 The problem is achieved in that before the introduction of alpha interferon, 3-5 sessions of cytapheresis are carried out by taking 1000-1200 ml of blood with its further centrifugation at a speed of 2000 rpm for 1 hour, followed by the isolation of blood cells and intravenous administration to the patient separated autoplasma with an interval of 3-4 days. The presented treatment method was applied in 11 patients with chronic viral hepatitis C with hemosiderosis of the liver. Extracts from medical records are given as an example.

 Example 1

 The history of the disease 1248. Patient X., 23 years. Diagnosis: Chronic viral hepatitis C with moderate activity, hemosiderosis III. Sick for 3 years. Not treated. The condition is satisfactory, the skin is icteric, the liver protrudes from the edge of the costal arch by 2 cm, the spleen is not palpable. In the analyzes: total protein 69.0 g / l, albumin 42%, gamma globulins 30%, sublimate test 1.7 units. , AlAT 1.6 mmol / L, bilirubin 39.0 μmol / L, Fe 45.0 μmol / L, ESR 30 mm / h, red blood cells 4.4 • 10 / L, hemoglobin 130 g / L, CEC 290 opt. units HCV Ab (+). In a morphological study of the liver, the lobular structure of the organ is preserved, granular, balloon, large-drop fatty degeneration of hepatocytes, moderate polymorphism of the nuclei, single bodies of Councilsilmen, a few focal, step, single bridge-like necrosis. The portal tracts are moderately expanded, fibrosed with the formation of septa, mainly lymphoid infiltration, proliferation of bile ducts. Dusty granules of pigment in hepatocytes. Hemosiderosis III Art.

 Treatment: Riboxinum, Festal, Vit. column B1, B6, C, 3 sessions of cytopheresis with an interval of 3 days, with a sampling of 1000 ml of blood, its further centrifugation at a speed of 2000 rpm for 1 h, isolation of 500 formed elements and intravenous administration of 500 autoplasms. In a further patient for 6 months, alpha-interferon was administered at 3 ml of ME subcutaneously three times a week for 6 months. After the treatment, the patient's condition improved - weakness, yellowness of the skin decreased. In the analyzes: total protein 66 g / l, albumin 43%, gamma globulins 22%, AlAT 1.0 mmol / l, bilirubin 18 μmol / l, sublimate sample 2 units, Fe 15.0 μmol / l, ESR 21 mm / h, red blood cells 3.2x10 / l, hemoglobin 112 g / l, CEC 110 opt. units HCV Ab (-).

 6 months after the end of treatment, the patient's condition is satisfactory, no complaints. In the analyzes: total protein 72 g / l, albumin 42%, gamma globulins 23%, AlAT 0.85 mmol / l, bilirubin 18.0 μmol / l, sublimate test 2.2 units. , Fe 20 μmol / l, ESR 18 mm / h, red blood cells 4.4 • 10 / l, hemoglobin 130 g / l, CEC 110 opt. units HCV Ab (-). In a morphological study of liver tissue, the organ architecture is preserved, a decrease in the manifestations of granular, balloon, and fatty degeneration of hepatocytes. A decrease in the number of necrosis, the severity of inflammatory infiltration in the portal tracts and parenchyma, the absence of Kaunsilmen's bodies, proliferation of bile ducts. Portal tracts are reduced in size. In hepatocytes, hemosiderin granules are absent.

 Example 2

 Case history 8911, patient M., 40 years old. Diagnosis: Chronic viral hepatitis C with pronounced activity at the stage of formed cirrhosis, hemosiderosis of the liver III. At admission, he complained of weakness, decreased performance, bloating, pain in the right hypochondrium, and the nose region. He was ill for about 19 years, when an enlargement of the liver was first detected. Not surveyed. About 3 years ago, the presence of HCV Ab was detected, was treated in a hospital without effect. Upon admission to the hospital, the condition is satisfactory, the skin is icteric, the stomach is swollen, the liver is dense, painless, protrudes 2 cm from the edge of the costal arch, the spleen is not palpated. In the analyzes: total protein 65 g / l, albumin 40%, gamma globulins 28.5%, sublimate assay 1.6 units, AlAT 1.9 mmol / l, bilirubin 36.4 mmol / l, Fe 48 μmol / l, ESR 40 mm / h, red blood cells 3.9 • 10 / l, hemoglobin 120 g / l, CEC 380 opt. units HCV Ab (+). Liver biopsy: lobular structure of the organ is disturbed due to the formation of false lobules, granular, hydropic, large and small droplet fatty degeneration of hepatocytes. Pronounced polymorphism of nuclei, violation of the integrity of the border plate, focal, stepwise, bridge-like necrosis of hepatocytes. The portal tracts are enlarged, fibrosed with the formation of septa, with severe lymphoid infiltration, proliferation of the bile ducts. On the periphery and centrolobularly in lobules, clumps and granules of iron-containing pigment are determined in more than 40%. Hemosiderosis III.

 Treatment: Essential, Riboxinum, Vit. B1, B6, C, festal, 4 sessions of cytapheresis with an interval of 4 days, with the collection of 800 ml of blood, its further centrifugation at a speed of 2000 rpm for 1 hour, the isolation of 350 uniform elements and intravenous administration of 450 autoplasma to the patient. After the end of cytapheresis, alpha-interferon 3 ml ME was administered subcutaneously three times a week for 6 months. After this therapy, the patient's condition improved - weakness, pain syndrome decreased, yellowness of the skin, bloating disappeared. In the analyzes: total protein 70 g / l, albumin 42%, gamma globulins 23%, AlAT 1.0 mmol / l, bilirubin 19 μmol / l, sublimate test 1.9 units, serum Fe 20 μmol / l, ESR 22 mm / h, erythrocytes 3.1x10 / l, hemoglobin 110 g / l, CEC 108 opt. HCV AB (-).

 6 months after the end of treatment: no complaints, the patient's condition is satisfactory. In the analyzes: total protein 70 g / l, albumin 41%, gamma globulins 23%, AlAT 0.96 μmol / l, bilirubin 17.0 μmol / l, sublimate sample 2.0 units. , Fe serum 22 μmol / L, ESR 20 mm / h, red blood cells 4.4 • 10 / L, hemoglobin 120 g / L, CEC 108 opt. units HCV Ab (-). Morphological examination of the liver: the lobular structure of the organ is violated due to the formation of false lobules. Granular, hydropic, fatty degeneration of hepatocytes, nuclear polymorphism significantly decreased. Single focal necrosis of hepatocytes is determined. Portal tracts decreased in size, fibrosed with the formation of septa. The intensity of portal tract infiltration is significantly reduced. There are no manifestations of bile duct proliferation in the portal tracts. Iron-containing pigment in the form of fine dusty grains is determined only in 5% of hepatocytes.

 Test case.

 The history of the disease is 1201, patient P., 33 years old. Diagnosis: Chronic viral hepatitis C with moderate activity, hemosiderosis III tbsp. On admission, he complained of weakness, aching pain in the right hypochondrium. Sick for about 7 years, when HCV was accidentally detected. Not treated. Objectively: the patient's condition is satisfactory, yellowness of the skin, the abdomen is slightly swollen, the liver is dense, protrudes 4 cm from the edge of the costal arch, the spleen is not palpable. In the analyzes: total protein 72 g / l, albumin 40%, gamma globulins 28.5%, AlAT 1.68 mmol / l, bilirubin 42, μmol / l, sublimate sample 1.7%, serum Fe 47 μmol / l, ESR 34 mm / h, red blood cells 4.4 • 10 / l, hemoglobin 130 g / l, CEC 280 opt. units HCV AB (+). During histological examination of the liver, the lobular structure of the organ is preserved, granular, small- and medium-droplet fatty degeneration of hepatocytes, moderate polymorphism of the nuclei, widespread focal and step necrosis, single bridge-like necrosis. The portal tracts are enlarged, moderately fibrosed with single septa, dense lymphoid infiltration, proliferation of the bile ducts, grade III hemosiderosis with pulverulent pigment granules, the response to orsein is positive in single cells.

 Treatment: Essential, Festal, Riboxinum, Vit. B1, B6, C, alpha-interferon 3 ml ME three times a week for 6 months. After this therapy, weakness and pain in the right hypochondrium decreased. Objectively: the condition is satisfactory, icteric integument, the liver protrudes from the edge of the costal arch by 1-2 cm, the spleen is not palpable. In the analyzes: total protein 70 g / l, albumin 41%, gamma globulins 25%, AlAT 1.2 mmol / l, bilirubin 26 μmol / l, sublimate sample 1.8 units, serum Fe 48 μmol / l, ESR 22 mm / h, red blood cells 4.5 • 10 / l, hemoglobin 129 g / l, CEC 188 opt. units HCV AB (+).

 6 months after the end of treatment, the patient complains of weakness, pain in the right hypochondrium. Satisfactory condition, yellowness of the skin, palpable enlarged dense liver 3 cm below the costal arch. The spleen is not palpable. In the analyzes: total protein 69.9 g / l, albumin 38%, gamma globulins 29%, AlAT 1.4 mmol / l, bilirubin 36 μmol / l, sublimate sample 1.6 units, serum Fe 46 μmol / l , ESR 35 mm / h, red blood cells 4.3 • 10 / l, hemoglobin 124 g / l, CEC 212 opt. units HCV Ab (+). Repeated biopsy of the liver: lobular structure preserved, granular, hydropic and fatty degeneration of hepatocytes, polymorphism of nuclei. The widespread focal, step and bridge necrosis of hepatocytes, portal tracts are enlarged, their fibrosis and number of septa with marked lymphoid infiltration, proliferation of bile ducts, hemosiderosis of the III degree, the response to orsenin is positive.

 The extracts from the case histories show that using the proposed method it is possible to treat patients with chronic viral hepatitis C with liver hemosiderosis with greater efficiency compared to the prototype by first removing excess iron from the liver tissue using cytapheresis.

 When the claimed method is presented in table. 1, after treatment, and also 6 months after the end of treatment, there was a lack of hemosiderosis in the liver, normal iron content, the absence of HCV Ab carriage in the blood, whereas in the prototype method after treatment, 1 hemosiderosis of the liver, high levels of iron and HCV AB in blood was saved. Data on the prototype method are presented in table. 2.

Claims (1)

A method of treating patients with chronic viral hepatitis C with hemosiderosis of the liver by administering α ₂ interferon, characterized in that the patient is preliminarily treated with 3-5 sessions of cytapheresis by collecting 800-1000 ml of blood with its further centrifugation at a speed of 2000 rpm. / min for 1 h, followed by the release of 350-500 ml of blood cells and intravenous administration of 450-500 ml of separated autoplasm to the patient with an interval of 3-4 days.

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