RU2477486C1 - Diagnostic technique for crossed forms of autoimmune liver diseases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: what is measured is the concentration of AMA-M2, ANA, AMA-M2+LKM, AMA-M2+sp100, AMA-M2+gp210, AMA-M2+F-Actin, AMA-M2+Desmin. If observing as follows: AMA-M2 172-200 Unit/ml, ANA 3.4-5.8 Unit/ml, AMA M2+LKM 1.8-2.8 Unit/ml, AMA-M2+sp100 2.7-4.5 Unit/ml, AMA-M2+gp210 1.6-2.4 Unit/ml, AMA-M2+F-Actin 1.0±1.4 Unit/ml and AMA-M2+Desmin 0.8-1.2 Unit/ml, a crossed form of autoimmune liver diseases is diagnosed.

EFFECT: improved diagnostic accuracy.

2 tbl, 3 ex

Description

The invention relates to medicine, in particular to internal medicine, and is intended for the diagnosis of patients with cross syndrome of autoimmune hepatitis and primary biliary cirrhosis.

A known method for the diagnosis of cross syndrome using the main serum markers of cholestasis and the level of immunoglobulins, as well as the titer of antimitochondrial antibodies [1 - Parés A., Caballería L. Rodés J. et al. Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver. Hepatol. 2000 Apr; 32 (4): 561-6].

A known method for the diagnosis of cross syndrome (PS) of autoimmune hepatitis and primary biliary cirrhosis (AIH / PBC) by determining antinuclear (ANA) and antimichondrial (AMA) antibodies (2 - Leishner U. Autoimmune liver diseases and cross syndrome. Anacharsis, M. - 2005 )

The aim of the present invention is to improve the accuracy of diagnosis of cross-forms of autoimmune liver diseases.

The technical result is achieved by determining the concentration of AMA-M2, ANA, AMA-M2 + LKM, AMA-M2 + sp100, AMA-M2 + gp210, AMA-M2 + F-Actin, AMA-M2 + Desmin and with an average value amounted to AMA-M2 - 172-200 U / ml, ANA - 3.4-5.8 U / ml, AMA-M2 + LKM 1.8-2.8 U / ml, AMA-M2 + sp100 - 2.7 -4.5 U / ml, AMA-M2 + gp210 - 1.6-2.4 U / ml, AMA-M2 + F-Actin - 1.0 ± 1.4 U / ml and AMA-M2 + Desmin - 0.8-1.2 U / ml.

The method is as follows.

Upon admission, they find out the presence of complaints of skin itching, mainly in the region of the anterior abdominal wall and lower extremities, intensifying at night, burping air, flatulence, general weakness. Appetite is reduced. Stool - constipation up to 3 days.

Medical history: Constipation has been a concern for many years. Marked skin itching, marked general weakness. According to biochemical blood tests, there is an increase in ACT, ALT, GGTP, alkaline phosphatase. According to the ultrasound study - an increase in the right lobe of the liver.

On admission: general condition: satisfactory. The patient is oriented in space, time. The skin and visible mucous membranes are yellowish, dry, warm. Small hepatic signs are present. No peripheral edema. The sclera is clean. The chest is involved in the act of breathing symmetrically. With auscultation, vesicular breathing. Upon receipt, the respiratory rate of 16-20 per min. Heart sounds are muffled, arrhythmic. Side-effects of heart activity are not heard. Pulse - normal filling voltage. Blood pressure: 130-150 and 70-90 mmHg The mucous membrane of the mouth is pale pink. Tonsils not enlarged. The tongue is wet. The abdomen is not enlarged, not swollen. With superficial indicative palpation, the abdomen is soft, painless, muscle tone of the anterior abdominal wall is normal. With deep palpation - moderately painful in the area of the projection of the head of the pancreas, in the epigastrium. There are no symptoms of peritoneal irritation. The liver protrudes from under the costal arch by 1-1.5 cm. The symptom of "striking" is negative on both sides.

INSTRUMENTAL RESEARCH DATA. With ECG: normal position of EOS. Sinus rhythm, correct. Marked diffuse changes in the myocardium.

ULTRASOUND RESEARCH of the abdominal organs: Acoustic access is satisfactory. Liver - an increase in the right lobe, the structure of the parenchyma is heterogeneous, echogenicity is increased, the contour is even. The visibility of the vascular structures is depleted. The bile ducts are not dilated. The portal vein with a diameter of 10 mm or more, the lumen is uniform, we pass. The gallbladder is of normal size, the contents are heterogeneous. The pancreas is usually located, the contours are uneven, fuzzy, the hepatic duct is not expanded. The spleen is enlarged. The splenic vein is not dilated. Free fluid in the abdominal cavity was not detected. Loops of the intestines are not expanded. Conclusion: diffuse changes in the liver, signs of chronic calculous cholecystitis, wrinkled gall bladder, chronic pancreatitis. Splenomegaly.

Puncture biopsy of the liver: some portal tracts are poorly infiltrated by lymphocytes, macrophages. In the portal tracts, small bile ducts lined with a single-layer cubic epithelium are defined, and lymphocytes between the epithelial cells. There are portal tracts with inflammatory infiltration without bile ducts. The integrity of the border plate in individual portal tracts is violated, the inflammatory infiltrate extends deep into the lobules. Step necrosis. Mixed intralobular infiltrates (lymphocytes, macrophages). Plots of hydropic dystrophy of hepatocytes. Hyperplasia of RES cells.

Indirect ultrasound fibroelastometry of the liver: liver elasticity from F0 to F2 according to METAVIR.

An immunological study determines the concentration of AMA-M2, ANA, AMA-M2 + LKM, AMA-M2 + sp100, AMA-M2 + gp210, AMA-M2 + F-Actin, AMA-M2 + Desmin. The average concentration was: AMA-M2 - 172-200 U / ml, ANA - 3.4-5.8 U / ml, AMA-M2 + LKM 1.8-2.8 U / ml, AMA-M2 + sp100 - 2.7-4.5 U / ml, AMA-M2 + gp210 - 1.6-2.4 U / ml, AMA-M2 + F-Actin - 1.0 ± 1.4 U / ml and AMA- M2 + Desmin - 0.8-1.2 U / ml. Diagnose the cross syndrome of autoimmune hepatitis and primary biliary cirrhosis.

The treatment was carried out with lezalon, ursosan, amaryl against the background of diet therapy (table No. 5). Positive treatment results confirmed the correctness of the selected criteria for the diagnosis of cross-forms of autoimmune liver diseases. Patients were discharged in satisfactory condition.

The method is further confirmed by examples of its implementation.

Example 1

Patient M., 52 years old, complains of skin itching in the anterior abdominal wall, mainly at night, general weakness, decreased performance and appetite. Stool - constipation up to 2-4 days.

From the anamnesis, it is known that several years ago the appearance of skin itching, marked general weakness, was noted. According to biochemical blood tests, there is an increase in ALT, ACT, GGTP, alkaline phosphatase. An ultrasound scan shows an increase in the right lobe of the liver.

Upon receipt, the general condition is satisfactory. The patient is oriented in space, time. The skin and visible mucous membranes are yellowish, dry, warm, with spider veins. No peripheral edema. With auscultation, vesicular breathing. The chest is involved in the act of breathing symmetrically. Respiratory rate 17 per minute. Heart sounds are muffled. Pulse - normal filling voltage. Blood pressure: 140 and 80 mmHg The mucous membrane of the mouth is pale pink. Tonsils not enlarged. The tongue is wet. The abdomen is not enlarged. With superficial indicative palpation, the abdomen is soft, painless, muscle tone of the anterior abdominal wall is normal. With deep palpation - moderately painful in the area of the projection of the head of the pancreas, in the epigastrium. There are no symptoms of peritoneal irritation. The liver protrudes from under the costal arch by 1 cm. The symptom of "striking" is negative on both sides.

With ECG: normal position of EOS. Sinus rhythm, correct. Marked diffuse changes in the myocardium.

Ultrasound examination of the abdominal organs: acoustic access is satisfactory, an increase in the right lobe of the liver is noted, the structure of the parenchyma is heterogeneous, echogenicity is increased, the contour is even. The visibility of the vascular structures is depleted. The bile ducts are not dilated. The portal vein with a diameter of 10 mm, the lumen is uniform, we pass. The gallbladder is of normal size, the contents are heterogeneous. The pancreas is usually located, the contours are uneven, fuzzy, the hepatic duct is not expanded. The spleen is enlarged. The splenic vein is not dilated. Free fluid in the abdominal cavity was not detected. Loops of the intestines are not expanded. Conclusion: diffuse changes in the liver, signs of chronic calculous cholecystitis, wrinkled gall bladder, chronic pancreatitis. Splenomegaly.

With a puncture biopsy of the liver: portal tracts are poorly infiltrated by lymphocytes, macrophages. In the portal tracts, small bile ducts lined with a single-layer cubic epithelium are defined, and lymphocytes between the epithelial cells. There are portal tracts with inflammatory infiltration without bile ducts. The integrity of the border plate in individual portal tracts is violated, the inflammatory infiltrate extends deep into the lobules. Mixed intralobular infiltrates (lymphocytes, macrophages). Plots of vacuole dystrophy of hepatocytes. Hyperplasia of RES cells.

Indirect liver ultrasound fibroelastometry: F1 liver elasticity according to METAVIR.

An immunological study determines the concentration of AMA-M2, ANA, AMA-M2 + LKM, AMA-M2 + sp100, AMA-M2 + gp210, AMA-M2 + F-Actin, AMA-M2 + Desmin. The concentration was: AMA-M2 - 172 U / ml, ANA - 3.4 U / ml, AMA-M2 + LKM 1.8 U / ml, AMA-M2 + sp100 - 2.7 U / ml, AMA-M2 + gp210 - 1.6 U / ml, AMA-M2 + F-Actin - 1.0 U / ml and AMA-M2 + Desmin - 0.8 U / ml. Diagnose the cross syndrome of autoimmune hepatitis and primary biliary cirrhosis.

The treatment with lezalon, ursosan was carried out against the background of diet therapy (table No. 5). Positive treatment results confirmed the correctness of the selected criteria for the diagnosis of cross-forms of autoimmune liver diseases. The patient was discharged in satisfactory condition.

Example 2

Patient K., born in 1966, was treated in the department of chronic liver diseases with a clinical diagnosis: Primary biliary cirrhosis, AMA M2 positive, class A (5 points) according to Child-Pugh. Chronic cholecystitis, remission. Chronic gastritis.

Upon receipt of a complaint of minor skin itching, weakness. Since the summer of 2009, the appearance of periodic skin itching in the palms and feet has been noted. At the end of August, weakness, sweating, and fatigue appear. From September 5, sharp pain in the right half of the chest joined, aggravated by movement, deep inspiration, fever up to 39 ° C, yellowness of the skin, dark urine. She was hospitalized in a joint venture to a hospital where, as a result of the diagnosis, no data on viral hepatitis were revealed. According to the results of biochemical blood tests, there was an increase in bilirubin 22 μmol / L, ALT 58 IU / L, ACT 71 IU / L, GGTP 51 IU / L, cholesterol 9. Against the background of the treatment (antibacterial therapy, pleural puncture, bronchodilators, NSAIDs) condition the patient improved - the temperature decreased, chest pain disappeared, however, according to the results of a biochemical blood test, insignificant transaminasemia remained up to 2 norms, the bilirubin level increased to 80 μmol / l, GGTP to 195 U / l. The patient was given a preliminary diagnosis - primary biliary cirrhosis. Ursosan 750 mg / day was prescribed. Upon receipt, the condition is satisfactory. Skin integument with areas of hyperpigmentation. In the lungs, vesicular breathing, no wheezing. BH 16 per minute. Heart sounds are muffled, rhythmic, heart rate 74 per min. HELL 130/70 mm Hg The abdomen is soft, painless. The liver protrudes 1.5 cm from the edge of the costal arch, the spleen is not palpable. The chair is regular, decorated. Urination is free.

Ultrasound examination showed that the size of the liver was increased, echogenicity was increased unevenly, and the visibility of the vascular structures was preserved. The gall bladder is 5.7 × 2.2 cm, no echoes were detected within the contour, the wall was 3.5 mm. The contents of the bubble are uniform. The common bile duct is within normal limits. Pancreas - size and echogenicity within normal limits. The spleen is not changed (S = 40 cm ² ). Gate vein 10 mm, splenic 6 mm. The size of the kidneys is not changed. Conclusion: signs of diffuse changes in the liver. Chronic cholecystitis.

ECG: EOS is not rejected. Sinus rhythm, heart rate 78 min. Fibroelastometry - fibrosis index F = 2 according to METAVIR.

Puncture biopsy of the liver: portal tracts are enlarged, fibrosed and infiltrated by a large number of lymphocytes mixed with macrophages. Ductulum proliferation is noted in portal tracts. Proliferating ducts and cells of inflammatory infiltrate violate the integrity of the border plate and extend deep into the hepatic lobules. "Empty" portal tracts. Small intracellular filtrates, epithelioid granulomas. Groups of lymphocytes, single plasma cells and neutrophils are often found in the lumen of extended sinusoids. Severe cell hyperplasia of the reticuloendothelial system. Morphological conclusion: Primary biliary cirrhosis 2 stages. Autoimmune hepatitis?

LABORATORY DATA At admission At discharge When post. At discharge hemoglobin 116 117 bilirubin 19 twenty red blood cells 4.79 4.8 cholesterol 10.7 9.6 white blood cells 4.7 5.2 Alkaline phosphatase 758 523 eosinophils 2 one GGTP 523 224 PO Box 2 2 AST 255 113 s / i 56 57 Alt 385 188 lymphocytes 36 35 glucose 5.7 4.6 monocytes four 5 Platelets 307 320 About. protein 82 81 ESR according to Westergain) 70 73 albumin 38 39 RMP for syphilis neg urea 3.8 3.9 [rothrombin 110 At HIV neg Blood type 0 (1) Rhesus +

An immunological study determines the concentration of AMA-M2, ANA, AMA-M2 + LKM, AMA-M2 + sp100, AMA-M2 + gp210, AMA-M2 + F-Actin, AMA-M2 + Desmin. The average concentration was: AMA-M2 - 200 units / ml, ANA - 5.8 units / ml, AMA-M2 + LKM 2.8 units / ml, AMA-M2 + sp100 - 4.5 units / ml, AMA- M2 + gp210 - 2.4 U / ml, AMA-M2 + F-Actin - 1.4 U / ml and AMA-M2 + Desmin - 1.2 U / ml. Diagnose the cross syndrome of autoimmune hepatitis and primary biliary cirrhosis.

The treatment with hepatoprotectors, fibrolytics on the background of diet therapy (table No. 5). Positive treatment results confirmed the correctness of the selected criteria for the diagnosis of cross-forms of autoimmune liver diseases. The patient was discharged in satisfactory condition.

Example 3

Patient V., born in 1954, who was being treated at the Department of Chronic Liver Diseases with a clinical diagnosis: Primary biliary cirrhosis, Child-Pugh class A. Chronic hepatitis C, HCV RNA is negative. Gastroesophageal reflux disease in the stage of reflux esophagitis. Chronic gastroduodenitis. Peripappillary diverticulum. Systemic scleroderma, limited form. Raynaud's Syndrome. Sjogren's syndrome. Chronic parenchymal mumps, xerostomia 2 tbsp. Hypertension 2 tbsp., Degree 1.

Upon enrolment. Complaints: itchy skin, bitterness and dry mouth, pain in the epigastric region, not associated with eating, heartburn. Stool - tendency to constipation, light brown, appetite maintained, body weight stable over the past 2 years.

From the anamnesis it is known that in 2000 complaints for the first time appeared about enlargement and swelling of the lacrimal glands, choking when taking “solid” food. In 2002, the examination diagnosed Sjögren’s disease. Metipred was prescribed 8 mg / day, leukeran; after a year, the dose of metipred was reduced to 4 mg / day (for the last 3 years, the patient independently canceled the frequency of administration - 1 table. after 2 days). In 2007 - diagnosed with systemic scleroderma. In 2006, hepatitis C virus etiology was diagnosed, minimal activity (antibodies detected). Since 2007, itchy skin has appeared. Diagnosed with primary biliary cirrhosis. Deterioration over the past 3 months, when epigastric pain intensified.

Upon receipt, the condition is satisfactory. The skin is of normal color with areas of hyperpigmentation. In the lungs, vesicular breathing, no wheezing. BH 16 per minute. Heart sounds are muffled, rhythmic, heart rate 74 per min. HELL 120/70 mm Hg The abdomen is soft, painless. The liver along the edge of the costal arch, the spleen is not palpable. The chair is regular, decorated. Urination is free.

ULTRASONIC STUDY: the size of the liver is increased (the thickness of the right lobe is 134 mm, the left is 63 mm), the echogenicity is increased unevenly, the visibility of the vascular structures is weakened. The gall bladder is 5.8 × 2.4 cm, no echoes were detected within the contour, the wall was 1.5 mm. The contents of the bubble are uniform. The common bile duct is within normal limits. Pancreas - size and echogenicity are within normal limits. The spleen is not changed (S = 35 cm ² ). Gate vein 10 mm, splenic 6 mm. The size of the kidneys is not changed. Conclusion: Signs of diffuse changes in the liver.

ECG: EOS semi-vertical. Sinus rhythm, correct; Heart rate 111 per minute. Diffuse changes in the myocardium. Endoscopy: Esophagitis. Cicatricial deformity of the stomach, gastritis, duodenitis, peripapillary diverticulum. Biopsy taken. Daily pH metrics - Conclusion: normocidal, pathological GER.

Biopsy of the gastric mucosa - foveolar hyperplasia HP-neg. The mucous membrane of the esophagus and small intestine without features.

Chest x-ray - the pulmonary fields are transparent, the pulmonary pattern is not changed. The roots are structural. The aperture is not changed. The borders of the heart are within normal limits, the aorta is not changed.

Fibroelastometry - fibrosis index F = 2 according to METAVIR.

LABORATORY DATA At admission When post. hemoglobin 131 bilirubin eleven red blood cells 4.4 Cholesterol 8.7 white blood cells 5.3 Alkaline phosphatase 121 eosinophils 3 GGTP 34 PO Box 2 AST 58 s / i 57 Alt 29th lymphocytes 32 glucose 5,6 monocytes 6 platelets 262 About. protein 71 ESR 26 albumin 42 RMP for syphilis neg urea 5.8 prothrombin 82 At HIV neg Blood type B (1P) Rhesus +

An immunological study determines the concentration of AMA-M2, ANA, AMA-M2 + LKM, AMA-M2 + sp100, AMA-M2 + gp210, AMA-M2 + F-Actin, AMA-M2 + Desmin. The average concentration was: AMA-M2 - 184 Units / ml, ANA - 4.2 Units / ml, AMA-M2 + LKM 2.0 Units / ml, AMA-M2 + sp100 - 3.2 Units / ml, AMA- M2 + gp210 - 1.8 U / ml, AMA-M2 + F-Actin - 1.2 U / ml and AMA-M2 + Desmin - 0.9 U / ml. Diagnose the cross syndrome of autoimmune hepatitis and primary biliary cirrhosis.

The treatment was carried out (ursosan 750 mg / day, omeprazole, metipred 4 mg / day) on the background of diet therapy (table No. 5). Positive treatment results confirmed the correctness of the selected criteria for the diagnosis of cross-forms of autoimmune liver diseases. The patient was discharged in satisfactory condition.

Claims (1)

A method for diagnosing cross forms of autoimmune liver diseases by determining antinuclear (ANA) and antimitochondrial (AMA) antibodies, characterized in that the concentration of AMA-M2, ANA, AMA-M2 + LKM, AMA-M2 + sp100, AMA-M2 + gp210, AMA-M2 + F-Actin, AMA-M2 + Desmin and with the value of AMA-M2 - 172-200 U / ml, ANA - 3.4-5.8 U / ml, AMA-M2 + LKM 1.8-2 8 U / ml, AMA-M2 + sp100 - 2.7-4.5 U / ml, AMA-M2 + gp210 - 1.6-2.4 U / ml, AMA-M2 + F-Actin - 1, 0 ± 1.4 U / ml and AMA-M2 + Desmin - 0.8-1.2 U / ml diagnose the cross form of autoimmune liver diseases.