Method for diagnosing hepatic cirrhosis

FIELD: medicine.

SUBSTANCE: method involves determining collagenase, collagenase inhibitor and protease inhibitor activity. Collagenase activity increasing to 4 mcmole/(l*h) and higher, protease inhibitor activity falling to 9 IU/ml and lower, collagenase inhibitor content falling to 1.9±0.2 IU/ml and lower, hepatic cirrhosis is to be diagnosed.

EFFECT: high accuracy and information capacity of the method.

 

The invention relates to the field of medicine, Hepatology and can be used for the diagnosis of cirrhosis of the liver.

A known method for the diagnosis of liver cirrhosis according to biopsy of the liver, where V.Desmetit et al (1994) define the stage of chronicity and assess the severity of fibrosis in histological preparations [6]. Way and Looseversion (1996) to assess the severity of fibrosis proposed histological index stages of chronicity of the process, where the authors on histological preparations of liver propose to consider not only the signs of portal and septal fibrosis, but sine (perceptuallybased) fibrosis. The known method for the diagnosis of stages of chronicity of the process gives good results a sufficient amount of liver tissue. However, needle biopsy of the liver with increasing fibrosis is difficult especially when already developed cirrhosis of the liver. It is necessary to consider the invasiveness of the method of needle biopsy and the impossibility of its execution because of the risk of possible complications (blood coagulation disorder with subsequent bleeding in cirrhosis of the liver). Difficulty of the procedure because of the refusal of the patient in the form of invasiveness of the method. You must often consider potential difficulties in the diagnosis of cirrhosis of the liver, because the liver is not always the enlarged but, on the contrary, reduced in size, especially as the clinical signs of cirrhosis virtually no, especially in the compensation stage of the process.

Closest to the present invention is a method for the diagnosis of cirrhosis by determining the relative content of the fractions of the effective absorption with added LFH), the relative content of sphingomyelin (SM), phosphatidylcholine phospholipid spectrum of blood and calculation of the ratio defined by the formula PF2/CM×LVH, where PF is the relative content of phosphatidylcholine, CM - relative content of sphingomyelin, LFH - relative effective absorption with added and values: 20-35 diagnosed chronic viral hepatitis, including the native HBsAg, 36-45 chronic viral hepatitis in persons who abuse alcohol, 50-96 diagnosed with cirrhosis [5].

However, this method is inaccurate, since the studies of phospholipid spectrum are in the blood, while the primary and the most pronounced changes in lipid metabolism occur in the hepatocytes of the liver, and the level of lipid peroxidation depends on the state of the antioxidant system [1]. The method is questionable, as it does not address the substantive issues, and carried out by a relative determination of phospholipid fractions spectrum of blood and are not accompanied by a parallel from the rising of the morphological status of the liver. So the diagnoses in this way look a little reliable. Finally, this method is far from diagnostic serum markers of fibrosis, as a last apply components of the extracellular matrix involved in the process of baked fibrinogenez, in particular, the imbalance of collagenase and its inhibitors, and tissue inhibitors of proteases.

A new technical challenge - improving the accuracy and informative way, extending the scope of its application.

The task to solve a new method for the diagnosis of cirrhosis of the liver, which consists in the examination of the patient with carrying out the biochemical analysis of blood and serum determine the activity of the collagenase activity of the inhibitor of collagenase and protease, and by increasing the activity of collagenase to 4 Ámol/l·h) and above, reducing the activity of the collagenase inhibitor to 1.9 S/ml and below, and reducing the activity proteasome inhibitor to 9 IE/ml and below diagnosed with cirrhosis of the liver.

The method is as follows

In the serum of the patient determine the activity of collagenase, collagenase inhibitor and protease and by increasing the activity of collagenase to 4 Ámol/l·h) and above, reducing the activity of the collagenase inhibitor to 1.9 S/ml and below, and reducing the activity proteasome inhibitor to 9 IE/ml and below the automotive technician is strout cirrhosis of the liver.

The proposed criteria are selected on the basis of the analysis of survey data of 60 patients with chronic hepatitis of various stages of chronicity and 20 patients with liver cirrhosis. The etiology of the disease - the virus (the virus C, b, b+C). All patients underwent General clinical examination and needle liver, Mangini with obtaining biopsy with subsequent morphological study and definition of histological activity index and the index of the stage of chronicity (index of fibrosis) and at the same time activities were determined in the blood serum of collagens [2], the activity of inhibitors of collagenase and proteases inhibitor [3].

In the group of patients with no fibrosis activity of collagenase in serum was not above 1,87 Ámol/l·h, in patients with liver cirrhosis - 4 Ámol/l·h, allowing to consider increasing the activity of collagenase as activation system collagenolysis in response to increased collagen synthesis [4]; cirrhosis of the liver activity of collagenase inhibitor in serum with no fibrosis was not lower than the 3.8 S/ml, and in the presence of cirrhosis, this figure had decreased to 1.9 S/ml and below; activity inhibitor in proteasome no fibrosis was not below 26,4 IE/ml, and in patients with cirrhosis of the liver she declined to 9.0 S/ml and below.

Cirrhosis of the liver increased activity of collagenase 3 and Bo is her time (4 Ámol/l· h) and above), reduced activity of collagenase inhibitor in 2 times (1,9 IE/ml and below) and reduced activity proteasome inhibitor, reflecting the decrease in protein synthetic function of the liver, 3 times (9 IE/ml and below).

Example 1. Patient P., 52 years old, diagnosed with cirrhosis of the liver, stage a (CALs-Drink) in history in the last 10 years is determined HBcorAgIgG, HBsAg, increased transaminase moderate nature of 1.5 times, moderate hepatomegaly, liver dense with a sharp edge. Complaints about General weakness, fatigue, examination revealed PCR for HBV DNA, increasing the activity of transaminases in 2 times. Study according to the proposed method. In serum - albumin 38 g/l, prothrombin index - 80, the activity of collagenase 4.4 Ámol/l·h, the activity of the collagenase inhibitor 1,7 IE/ml, the activity proteasome inhibitor of 8.5 S/ml. histological examination of the liver - liver cirrhosis in the active phase.

Example 2. Patient, 56 years history of frequent donation and blood transfusion about uterine bleeding 10 years ago. Periodically an increase in the level alanine-notransferase, deterioration of health in the last 3 years. When examined in terms of Hepatology Department has a positive PCR for HCV RNA, transaminase activity was increased 1.5 times, the ultrasound hepato and splenomegaly/. Conducted policy research and the study according to the proposed method. Serum albumin 35 g/l, prothrombin index 78, the activity of collagenase - 4.6 Ámol/l·h, the activity of the collagenase inhibitor 1,6 IE/ml, the activity proteasome inhibitor of 8.3 S/ml. histological examination of the liver diagnosed with cirrhosis of the liver active phase.

Example 3. Patient C., 41 year history in the last 10 years the use of intravenous drugs (opium addiction). Periodically increased transaminase not more than 2 times in the blood during this time a positive PCR for HCV RNA. Study according to the proposed method. Serum for admission has decreased albumin 33 g/l, prothrombin index 78, the activity of collagenase 4.8 Ámol/l·h, the activity of the collagenase inhibitor 1,7 IE/ml, the activity proteasome inhibitor of 8.1 S/ml. of the core biopsy showed cirrhosis moderate activity.

Thus, the proposed method allows a non-invasive examination with determination of biochemical parameters of blood serum on the activity of collagenases, the activity of inhibitors of collagenase and protease.

Application of the proposed non-invasive method of research allows us to diagnose cirrhosis of the liver, i.e. to evaluate the structure of the liver, and during follow-up without puncture biopsy is echani to evaluate the results of treatment, in terms of the increase in cirrhotic changes, either in the stabilization parameters.

Sources of information

1. Dunaevsky O.A. Viral hepatitis and differential diagnosis of liver diseases. - Tver, 1993. - 263 S.

2. Sharayev I.N., Peskov V.N., Zvorykina N.G. Determination of collagen activity of blood plasma // Laboratory work. - 1987. No. 1. - P.60-62.

3. Nartova V.F., Pashina FORCE Uniform method for determining the activity α2-macroglobulin in serum (plasma) human blood // the Questions of medical chemistry. - 1979. - V.25, No. 4. - S-499.

4. Loginov A.S., Block J.E. Chronic hepatitis and cirrhosis of the liver. Medicine, 1987.

5. Patent No. 2167424 method for the diagnosis of chronic liver diseases. Author Makarov VK

6. Desmetit V., Gerber, M., et al. Classification of chronic hepatitis, diagnosis, determine the severity and gravity of the current // Russian journal of gastroenterology, Hepatology and Coloproctology. - 1995. No. 2. - Đ.38-45.

A method for the diagnosis of cirrhosis of the liver, which consists in the examination of the patient and conducting biochemical studies of blood, wherein the blood serum to determine the activity of collagenase, collagenase inhibitor and protease and by increasing the activity of collagenase to 4 Ámol/l·h) and above, reducing the activity of the collagenase inhibitor to 1.9 S/ml and below and the decrease of activity is inhibitor protease to 9 IE/ml and below diagnosed with cirrhosis of the liver.



 

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