RU2549963C1 - Method of predicting development of critical hepatic failure basing on selenium level in serum - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: determined are: prothrombin time (PTT, sec) and serum level of selenium (SE mkg/l), as well as ultrasonic indices of the portal vein diameter (dVP, mm). A coefficient k is calculated in units by formula

the probability of lethal outcome within 20 days is evaluated on the basis of the obtained result. If the values of the said coefficient k are higher than 3.8 units, lethal outcome is predicted, if k value is lower or equal 3.8 units favourable outcome is predicted, which makes it possible to continue treatment in the volume of the somatic department.

EFFECT: method makes it possible to increase the efficiency and reliability of diagnostics of cirrhosis decompensation and provide the timely correction of the carried out therapy.

1 tbl, 3 ex

Description

The invention relates to medicine, namely to hepatology, and can be used to predict the development of critical liver failure and the onset of death in patients with decompensated liver cirrhosis of alcoholic and mixed (alcoholic and viral) etiology based on serum selenium level.

The most significant mechanism for the development of decompensation of alcoholic liver disease in the form of alcoholic cirrhosis is hypoxia. In turn, one of the damaging factors of hepatocytes at the membrane level is the activation of lipid peroxidation (Vengerovsky A.I., Baturina N.O., Chuchalin V.S., Saratikov A.S. The role of lipid peroxidation in the mechanism of fibrous tissue proliferation liver in experimental chronic hepatitis // Patol. physiol. and experimental therapy. - 1996. - No. 2. - S. 37-39). In contrast to free radical processes in the body there is an antioxidant system. A special place in it is occupied by the glutathione system, the key components of which are selenium-containing enzymes. These provisions allow us to look at hepatocellular insufficiency during decompensation of cirrhosis of alcohol and mixed etiology as a dynamic mismatch between the current needs of the body in selenium and liver functional capabilities, which are manifested in a change in indicators.

The closest known analogues of the prototype of the investigated method are the following methods for predicting the onset of death in patients with cirrhosis of the liver: a) determination of serum levels of creatinine, bilirubin (patent for invention No. 2373533 "Method for predicting the onset of death in patients with cirrhosis of the liver of viral and alcoholic etiology" from 10.27.2008); b) serum levels of creatinine, bilirubin and determination of MHO (international normalized ratio), followed by calculation on the MELD scale (model for end-stage liver disease) of values (Durand F., Valla D. Assessment of prognosis of cirrhosis Semin Liver Dis. 2008; 28 (1): 110-22.). However, the disadvantage of these methods is the long-term prognosis, which cannot be used in acute liver failure. Another disadvantage is the difficulty of calculating the necessary values according to the formula, which complicates the use of the described methods in practical medicine. In addition, using the MELD method, the probability of a fatal outcome in a patient population is determined, however, it does not allow an individual prognosis, namely, to determine the probability of a fatal outcome in a particular patient. Since MELD was developed for a patient population in the USA, there may be limitations in the applicability of this method in patient populations of other countries.

There are also prototype methods for predicting the onset of death in patients with cirrhosis of the liver according to the Child-Turcotte-Pugh scale (Child C.G., Turcotte JG Surgery and portal hypertension. In: The liver and portal hypertension. Edited by CG Child. Philadelphia: Saunders 1964: 50-64. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. "Transection of the oesophagus for bleeding oesophageal varices". Br J Surg. 1973; 60 (8): 646-9) and on the Orlov-Dudnik scale (patent for invention No. 2482786 "A method for predicting the course of chronic viral hepatitis B and C" from 11/30/2011). The disadvantage of these methods is the determination of qualitative indicators such as ascites, encephalopathy, etc., the clinical interpretation of which may differ from one researcher to another, which leads to prognostic differences. In addition, the disadvantages of the Orlov-Dudnik scale are multicomponentness, which impedes its practical application, as well as the possibility of using the scale only for viral hepatitis B and C.

There is also a method for predicting the progression of liver failure by analyzing the metabolism of calcium and copper (Blyuger A.F., Novitsky I.N. Practical hepatology. - Riga, 1984, 47 pp.), However, the accuracy of predicting the progression of liver failure for one trace element is limited.

Studies of the effects of selenium and blood coagulation indices taking into account ultrasound data of portal hypertension on the prognosis of fatal outcome in patients with decompensated liver cirrhosis of alcoholic and mixed etiology were not found in the literature available to us. Studying only the amount of selenium or indicators of the blood coagulation system are not always sufficiently informative methods for predicting the development of critical liver failure. The invention is aimed at improving the efficiency and reliability of the diagnosis of tissue hypoxia during decompensation of cirrhosis, which helps to correctly determine the severity of hepatic pathology, predicting the course of the pathological process in the liver and ensuring timely correction of therapy and treatment tactics.

The objective of the invention: to propose a method for predicting the development of critical liver failure based on the serum level of selenium, devoid of the above disadvantages, which allows predicting the onset of death in patients with decompensated liver cirrhosis of alcoholic and mixed etiology.

The technical result of the invention is that it is possible to increase the accuracy of predicting the onset of death in patients with decompensated liver cirrhosis of alcoholic and mixed etiology at predetermined time intervals (20 days) by examining the product of prothrombin time (PTV, sec), portal vein diameter (dVP, mm), and their ratio with the content of selenium in the blood serum (SE, μg / L).

The technical result is achieved by quantitatively determining the content of selenium in blood serum by a fluorimetric method in μg / l (Golubkina N.A. Fluorimetric method for determining selenium // Journal of Analytical Chemistry. - 1995. - T. 50, No. 5. - P. 492-497 ), determination of prothrombin time in a coagulometer with a mechanical principle of recording results in seconds and ultrasonic measurement of the portal vein diameter in millimeters.

A study of 26 patients with decompensation of liver cirrhosis of alcoholic and mixed (alcoholic and viral) etiology, with an assessment of the final hard point - the onset of a fatal outcome from liver failure or its complications, was conducted on the basis of hospital No. 7 in Khabarovsk. We examined 12 men and 14 women aged 32 to 74 years (Me = 50 years). The diagnosis of cirrhosis of the liver of alcoholic and mixed etiology, decompensation was established on the basis of signs of diffuse damage to the liver, hepatic cell failure syndrome, portal hypertension syndrome. The etiology was determined by a history of long-term alcohol abuse and data from a virological study of blood serum on hepatitis B virus markers (HBsAg, a / t classes M and G to HBcorAg, HBV DNA), C (a / t classes M and G to HCV, RNA HCV) and D (a / t to HDV). Patients with severe concomitant pathology were excluded from the study. The observation period was 20 days. Over the entire observation period, 8 patients died. All patients with CP were divided into 2 groups: survivors were included in group 1, and the dead in group 2. The comparison group consisted of 7 men and 8 women aged 20-50 years without clinical manifestations of the pathology of the hepatobiliary system, the average daily dose of alcohol being less than 33 g in terms of 96% alcohol. Statistical data processing was carried out using the program Statistica v6.0 (StatSoft, USA).

в программе Microsoft Excel 2010 по табличным данным. В контрольной группе и первой группе пациентов коэффициент

ниже или равно 3,8 единиц. Исход - наблюдались в течение 20 дней, летальных случаев не выявлено. У пациентов второй группы, у которой коэффициент

превысил 3,8 единицы, в течение 20 дней после госпитализации наблюдался летальный исход.The study found that independent factors of an unfavorable prognosis of the development of critical liver failure in patients with decompensated liver cirrhosis of alcoholic and mixed etiology are: prolongation of prothrombin time, as an indicator of liver cell failure; decrease in serum selenium level as an indicator of activation of lipid peroxidation processes. And also such factors include an increase in the diameter of the portal vein, as an indicator of portal hypertension. The research results are shown in table 1. For ease of use, we proposed a coefficient k calculated by the formula

in Microsoft Excel 2010 using tabular data. In the control group and the first group of patients, the coefficient

less than or equal to 3.8 units. Outcome - observed within 20 days, no fatal cases were detected. In patients of the second group, in which the coefficient

exceeded 3.8 units; within 20 days after hospitalization, a fatal outcome was observed.

This led to the conclusion that the ratio of the product of prothrombin time (PTV, sec) and portal vein diameter (dVP, mm) to serum selenium content (SE, μg / l) in individuals with alcoholic and mixed (alcoholic) liver cirrhosis and viral) etiology, it is possible to predict the onset of a fatal outcome, in order to avoid which it is recommended to carry out preventive correction of pathological manifestations to reduce the severity of the condition of patients.

Advantages of the proposed method:

- timely prediction of the development of critical liver failure based on the serum level of selenium allows to achieve a positive economic effect by timely determining the amount of medical care and eliminating the facts of drug use, the use of which will not allow to achieve the desired result;

- the method is informative;

- the sampling of the material is technically simple and does not require special knowledge from the staff;

- the proposed forecasting method can be applied in any medical institution, regardless of its level;

возможно не долгосрочное прогнозирование наступления летального исхода, позволяющее своевременно принять решение о переводе больного в реанимационное отделение для начала интенсивной терапии;- by coefficient

perhaps not long-term prediction of the onset of a fatal outcome, allowing you to make a timely decision on the transfer of the patient to the intensive care unit to start intensive care;

технически прост.- calculation of the coefficient

technically simple.

Examples of the application of the forecasting method.

Example 1

2,9 единиц. По способу-прототипу определена тяжесть цирроза печени - класс C (10 баллов), индекс MELD - 75, что дает неблагоприятный исход. На основании предложенного способа не прогнозируется наступление летального исхода. Исход: больной выписан из стационара на 34 сутки.Patient K., 41 years old, was admitted with a diagnosis of liver cirrhosis of alcoholic etiology, decompensation, ascites. The real deterioration arose after the next episode of alcohol consumption. An objective examination - hepatic encephalopathy 2 stages. In the biochemical analysis of blood - albumin 31 g / l, total bilirubin 219.5 μmol / l, ACT 380 U / l, creatinine 150 μmol / l, PTV 16.5 sec, MHO 1.3, serum selenium content 81 μg / l According to ultrasound, the portal vein diameter is 14 mm, ascites 2.7 liters. Coefficient

2.9 units. By the prototype method, the severity of cirrhosis of the liver was determined - class C (10 points), the MELD index - 75, which gives an unfavorable outcome. Based on the proposed method, the onset of death is not predicted. Outcome: the patient was discharged from the hospital on the 34th day.

Example 2

7,2 единиц. По способу-прототипу определена тяжесть цирроза печени - класс B (7 баллов), индекс MELD - 74, выживаемость в течение года - 80%. На основании предложенного способа прогнозируется наступление летального исхода. Исход: через 8 дней у обследованной пациентки манифестировала клиника кровотечения из варикозных вен пищевода, больная переведена в хирургическое отделение, больная скончалась.Patient J., 64 years old, was admitted with a diagnosis of cirrhosis of the liver of mixed etiology (alcoholic + HCV), decompensation. The real deterioration arose after the next episode of alcohol consumption. An objective examination - no hepatic encephalopathy. In the biochemical analysis of blood - albumin 34 g / l, total bilirubin 64.9 μmol / l, ACT 89 U / l, creatinine 121 μmol / l, PTV 21.9 sec, MHO 2.1, serum selenium content 49 μg / l According to ultrasound, the diameter of the portal vein is 16 mm, there is no fluid in the abdominal cavity. Coefficient

7.2 units. According to the prototype method, the severity of cirrhosis of the liver was determined - class B (7 points), MELD index - 74, survival rate during the year - 80%. Based on the proposed method, the onset of death is predicted. Outcome: after 8 days, a clinic of bleeding from varicose veins of the esophagus manifested itself in the examined patient, the patient was transferred to the surgical department, the patient died.

Example 3

7,7 единиц. По способу-прототипу определена тяжесть цирроза печени - класс C (13 баллов), индекс MELD - 87, выживаемость в течение месяца - 11%, одного года - 2%. На основании предложенного способа прогнозируется наступление летального исхода. Исход: через 2 дня пребывания в стационаре у больной развилась печеночная кома и больная умерла.Patient U., 45 years old, was admitted with a diagnosis of cirrhosis of the liver of mixed etiology (alcoholic + HCV), decompensation, ascites. The real deterioration arose after the next long episode of alcohol consumption. An objective examination - hepatic encephalopathy 2 stages. In the biochemical analysis of blood - albumin 29 g / l, total bilirubin 438.9 μmol / l, ACT 101 U / l, creatinine 190 μmol / l, PTV 22.3 sec, MHO 2.3, serum selenium content 52 μg / l According to ultrasound, the diameter of the portal vein is 18 mm, and the fluid in the abdominal cavity is 1.7 liters. Coefficient

7.7 units. According to the prototype method, the severity of cirrhosis of the liver was determined - class C (13 points), MELD index - 87, survival for a month - 11%, one year - 2%. Based on the proposed method, the onset of death is predicted. Outcome: after 2 days of hospitalization, the patient developed hepatic coma and the patient died.

Claims (1)

A method for predicting the development of critical liver failure and a possible fatal outcome in patients with decompensated liver cirrhosis of alcoholic and mixed (alcoholic and viral) etiology based on serum levels of selenium, including laboratory and ultrasound examinations of the patient, characterized in that prothrombin time (PTV, sec), portal vein diameter (dVP, mm) and serum selenium content (SE, μg / L), then using these data, the coefficient k is calculated by the form le

and with a value of k less than or equal to 3.8 units, a favorable outcome is predicted for 20 days, which allows you to continue treatment of the patient in the somatic department, and with values of k above 3.8 units, a lethal outcome is predicted at the same time, and a decision is made on transferring a patient to the intensive care unit.