RU2465818C1 - Method for prediction of fatal outcomes in patients suffering viral or alcoholic cirrhosis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, specifically to gastroenterology. Multilevel neurodynamic analysis of cardiorhythmogram is conducted with the use of a rhythmocardiograph and Omega-S hardware and software complex. The following indices are evaluated: A is a contingency of all, but preferentially peripheral rhythm processes, B1 is a degree of balance of sympatic and parasympatic effects on a cardiac pacer, C1 is a state of central subcortical regulation, D1 is a state of central cortical regulation. The onset of the fatal outcome (U_fatal) in the patients suffering viral or alcoholic cirrhosis is calculated by formula: U_fatal = -2.217+0.031*A+0.064*B1+0.012*C1+0.025*D1. The U_fatal value less than -0.41 enables predicting the fatal outcome in the given category of patients for 6 months after the examination.

EFFECT: method provides higher prediction accuracy.

5 tbl, 3 ex

Description

The invention relates to medicine, namely to gastroenterology, and relates to a method for predicting death in six months in patients with cirrhosis of the liver (CP) of viral or alcoholic etiology. The method can be used in hospitals, clinics, diagnostic centers.

At present, predicting the course of CP and its complications is important for the timely determination of therapeutic tactics. The determination of an accurate individual prognosis is also important for solving social and psychological issues (obtaining a disability group, moral preparation of the patient's relatives for a probable outcome, drawing up a will).

Currently, one of the methods for predicting death in patients with cirrhosis is the method of determining hepatic cell dysfunction according to Child - Pugh (10-year survival), including the assessment of qualitative clinical indicators (presence or absence of ascites, encephalopathy) and quantitative (serological levels of bilirubin , albumin and prothrombin index - PTI) and subsequent calculation on a scale [1]. Indicators are assigned scores from 1 to 3. Ascites (absent - 1 point, controlled - 2 points, refractory - 3 points), encephalopathy (absent - 1 point, minimum - 2 points, pronounced - 3 points), bilirubin (less than 34 μmol / l - 1 point, 34-51 μmol / l - 2 points, more than 51 μmol / l - 3 points), albumin (more than 35 g / l - 1 point, 28-35 g / l - 2 points, less than 28 g / l - 3 points), IPI (more than 50% - 1 point, 40-50% - 2 points, less than 40% - 3 points). Then all points are summarized and patients are divided into 3 classes: class A (5-6 points), class B (7-9 points) and class C (10-15 points). In patients with a higher score or class, death is predicted earlier than in patients with a lower score. The method allows to predict the onset of death in the population of patients with CP within 10 years after the examination.

The disadvantage of this method is the determination of qualitative indicators (ascites and encephalopathy), the clinical interpretation of which may differ from one researcher to another, which leads to prognostic differences [2, 3]. The method is convenient for creating a priority in the waiting list for liver transplantation, but does not allow to determine an individual prognosis, i.e. the probability of a fatal outcome in a particular patient within a significantly shorter period of time, that is, within 6 months after the examination.

There is also a method for predicting death in a population of patients with CP, including the determination of serum levels of creatinine, bilirubin and the determination of MHO (international normalized relationships), followed by calculation on the MELD (model for end-stage liver disease) model of values corresponding to sequences of lethal outcomes in the population of patients with CP [2]. Fatal outcome is predicted by the value of R: R = 9.6 × log _e (creatinine mg / dl) + 3.8 × log _e (bilirubin mg / dl) × 11.2 × log _e (INR) + 6.4. Empirically, the maximum value of R is 40, and the minimum is 6. Therefore, the MELD scale is a continuous variable with values from 6 to 40 [4]. Patients with higher R values of CP die earlier than patients with lower R values. The method has sufficient predictive accuracy in predicting the survival of CP patients who underwent transugular intrahepatic bypass surgery [5]. According to the above method, using the MELD scale, it is possible to determine the probability of a fatal outcome in a patient population, however, it does not allow determining the probability of a fatal outcome in individual patients (individual prognosis). The MELD scale was developed for a patient population in the United States, which may give limitations on the applicability of this method in other patient populations, in particular in Russia.

The accuracy of the prognosis of a fatal outcome in CP recommended for use in practice should be at least 70% [3]. Therefore, the threshold of 70% is defined as the minimum, at which it is advisable to apply the proposed methods.

The closest in technical essence to the claimed method and we have chosen as a prototype is a method for predicting the onset of death in patients with cirrhosis of the liver, viral and alcoholic etiology at specified intervals (one, three and six months), developed in Tomsk in 2008 . (patent RU No. 2373533). The method consists in determining the biochemical parameters of blood - serum levels of aspartate aminotransferase (ACT, Unit / L) and creatinine (μmol / L), with a 75% probability of a fatal outcome within six months after the examination, which is calculated by the formula:

Where

P is the probability of a fatal outcome (in%),

e is a mathematical constant = 2.72,

b ₀ is the constant of the regression equation,

b ₁ - regression coefficient for ACT,

b ₂ - regression coefficient for creatinine, while:

for six months, b ₀ = -3.1898, b ₁ = 0.008796, b ₂ = 0.016355, and at P> 50%, a fatal outcome is predicted.

The disadvantage of the prototype is the lack of accuracy of the method.

The technical result of the invention is to improve the accuracy of the method for predicting death in patients with cirrhosis of the liver of viral and alcoholic etiology within 6 months after the examination.

The technical result is achieved by the fact that in patients with cirrhosis of the liver of viral and alcoholic etiology, using a rhythm cardiograph and the Omega-S software and hardware complex, a multilevel neurodynamic analysis of cardiac rhythmograms is carried out, the following indices are determined, which reflect “A” - the conjugation of all, but mainly peripheral rhythmic processes, “B1” - the degree of balance of sympathetic and parasympathetic influences on the sinus node of the heart, “C1” - the state of central subcortical regulation, "D1" - the state of central cortical regulation with subsequent calculation of the probability of a fatal outcome in patients with cirrhosis of the liver of viral or alcoholic etiology according to the formula: _Exod = -2.217 + 0.031 * A + 0.064 * B1 + 0.012 * C1 + 0.025 * D1, and when a value of Y _outcome less than -0.41 predict a fatal outcome in this category of patients within 6 months after the examination.

The method is as follows.

When implementing the method, a simultaneous multilevel neurodynamic analysis of cardiac rhythmograms is used (patent RU No. 2233616, 2004 - Method for diagnosing disorders of central neurohormonal regulation and patent RU No. 31943, 2003 - Device for forming heart rhythmograms). We used Omega-S PAK (manufacturer LLC MedKosmos-E, Russia, Moscow). For the same purpose, a rhythm cardiograph such as "Valenta +" can be used.

When conducting a multilevel neurodynamic analysis of cardiac rhythmograms, the patient is excluded from exposure to irritating factors: physical exertion, talking, and sharp sounds. The study does not include patients with complex cardiac arrhythmias, confirmed by cardiac electrocardiography (ECG), and using antiarrhythmic therapy, due to the influence of these factors on the examination results.

To predict the lethal outcome in patients with cirrhosis of the liver of viral and alcoholic etiology, the following indices are evaluated, obtained during simultaneous multilevel neurodynamic analysis of cardiac rhythmograms [6, 7]:

“A” - Conjugation of all, but mainly peripheral, rhythmic processes (fractal analysis of the general rhythmic pattern of the system-regulatory activity of the body, assessment of the level of long-term adaptation).

“B1” - Vegetative balance (degree of balance of sympathetic and parasympathetic influences on the sinus node of the heart, assessment of the level of current adaptation).

“C1” - Central subcortical regulation (neurodynamic analysis of pacemaker control codes generated at the level of GGNK, short-term forecasted assessment of the level of adaptation).

“D1” - Functional activity of the cortex (neurodynamic analysis of pacemaker control codes formed at the level of the cerebral cortex, short-term predicted assessment of the level of psychofunction).

The probability of a fatal outcome within six months is calculated according to the formula: _outcome = -2.217 + 0.031 * A + 0.064 * B1 + 0.012 * C1 + 0.025 * D1. If the value is less than -0.41 V _starting predict death in patients with viral cirrhosis and alcoholic etiology for 6 months.

Distinctive essential features of the proposed method are:

- using a rhythm cardiograph and the Omega-S hardware-software complex, a multilevel neurodynamic analysis of cardiac rhythmograms is carried out, the following indices are determined, reflecting - “A” - the conjugation of all, but mainly peripheral rhythmic processes, “B1” - the degree of balance of sympathetic and parasympathetic influences on sinus node of the heart, “C1” - the state of central subcortical regulation, “D1” - the state of central cortical regulation.

- the probability of a fatal outcome within six months is calculated by the formula: Y _outcome = -2.217 + 0.031 * A + 0.064 * B1 + 0.012 * C1 + 0.025 * D1;

- if the _{outcome of} less than -0.41 V predict death in patients with viral cirrhosis and alcoholic etiology for 6 months after the test.

A causal relationship between the salient features and the effect achieved:

- With CP, there is a lesion of the cardiovascular system, due to neurorefractory, dyselectrolyte and dysmetebolic disorders. The main factors affecting the state of the cardiovascular system in patients with CP are: an increase in hepatic cell failure, cytolytic and cholestatic syndromes. Violations of the hemodynamics of the liver (portal hypertension) in CP triggers a cascade of autonomic, neurohumoral and metabolic reactions that cause changes in central hemodynamics, that is, the heart, therefore they perform a multilevel neurodynamic analysis of cardiac rhythmograms using a rhythmocardiograph.

- The method of multilevel neurodynamic analysis of cardiac rhythmograms allows not only to evaluate the statistical and variational indicators of cardiac rhythm and through them the degree of tension of vegetative regulation, cardiac activity, but also provides information on the functioning of the central links of systemic regulation (cerebral cortex and the region of GTNK) and the whole organism ( fractal portrait ”) [7, 8, 9].

This technology is based on the principle of a monoparametric multilevel analysis of the state of system regulation by extracting stable, repetitive, noise-invariant neurodynamic codes that are contained in any rhythmograms (in this technology, in cardiorhythmograms). The process of their extraction is called neurodynamic decoding. The physiological decoding of these codes gives an idea of the type, pace and direction of the pathological process, which allows you to evaluate the current and future degree of severity of the patient and to manage the therapeutic activity.

The multilevel neurodynamic analysis of cardiac rhythmograms involves the registration of 300 cardiocycles. After that, 5 rhythmograms are automatically extracted from the original graphic recording [6, 7]:

- R-R intervalogram - a sequence of R-R intervals

- R-P intervalogram - a sequence of R-P intervals

- R-T intervalogram - a sequence of R-T intervals

- The ratio of the amplitudes R and T of the teeth - a sequence of values of the ratio of the amplitudes R and T of the teeth

- Duty rate EX - a sequence of values of the ratio of the period following the cardiocomplex to its duration.

All 5 rhythmograms are converted from analog to digital format and transferred to a computer for subsequent software conversion. The second stage of the software processing of the initial recording of the cardiointervalogram is divided into 4 stages. At the first stage, a set of methods was used for statistical and variational estimation of the only standard R-R cardiorhythmogram (program “B” indices). At the second stage, neurodynamic analysis of all 5 cardiac rhythmograms (indexes “C” of the program) was used. At the third stage, neurodynamic analysis of the artificially synthesized pseudoencephalogram (indexes “D” of the program) is used, and at the fourth stage, the conjugation of all rhythmic processes occurring in the body (index “A” of the program) is evaluated. In the first three stages, a lot of intermediate parameters are calculated, which are grouped into two indexes (B1, B2, C1, C2, D1, D2). All indices with the number 1 are assigned to the indicators of the so-called “fast” regulation, and indices with the number 2 are assigned to the indicators of the “slow” regulation.

The indices we selected, that is, “B1” - the degree of balance of sympathetic and parasympathetic influences on the sinus node of the heart, “C1” - the state of central subcortical regulation, “D1” - the state of central cortical regulation - have the greatest sensitivity and reflect the change in the state of rapid general organization regulation, while index A is the conjugation of all, but mainly peripheral rhythmic processes, reflects the state of all general regulatory processes (fast and slow) (RF Patent No. 2233616, 2004 - A method for diagnosing disorders of central neurohormonal regulation).

The meaning of this diagnostic technology is to assess the quality of the corporate (system) regulation, through the evaluation of the quality of control codes. Reference codes are age and gender independent and always reflect the ideal degree of adaptability of the body. Change of codes for any chronic diseases occurs according to one scenario, which reflects the degree of adaptation - maladaptation of the body in response to the action of certain damaging factors. Therefore, the technology in its methodological orientation is alternative to most of the diagnostic technologies used, serving the methodology of multiparameter description of individual organofunctional subsystems of the body.

The consequence of changing the methodological approach is the possibility of obtaining prognostic information, because the change in the parameters of the control codes occurs much earlier than the shifts in the peripheral organs and tissues to which these regulatory influences are directed. This happens due to the vertical functional hierarchy of regulatory structures. In practice, this allows us to predict the risk of complications by the totality of regulatory criteria [7, 10]. This method of system-regulatory neurodynamic assessment of cardiac rhythmograms provides information on the functioning of the heart rate regulation system, which includes 4 levels:

a) the level of autonomic homeostasis, reflecting the assessment of the balance of peripheral autonomic influences on the sinus node of the heart;

b) the level of activity of the hypothalamic-pituitary neurohormonal complex (GGNA), which determines the state of central subcortical regulation;

c) the level of activity of the cerebral cortex, reflecting the state of central cortical regulation;

d) the level of balance of mainly peripheral rhythms of the body (the so-called "fractal portrait of the body").

The 4-level model of heart rate regulation is virtual, but the information obtained with its help is quite real, but cannot be obtained by methods that study specific structural and morphological formations of the cardiovascular or neuro-endocrine system. This happens because the coordinated functioning of all sublevels and subsystems of the body is carried out due to the action of unified control codes, which differ in different organs and structures only in their spatial and temporal dimension.

The creation of a new method for predicting death in patients with cirrhosis of the liver of viral and alcoholic etiology through multilevel neurodynamic analysis of cardiac rhythmograms was carried out on the basis of the Department of Internal Medicine with a course of therapy and nephrology of the Faculty of Continuing Education of St. Petersburg State Medical Academy I.I. Mechnikova.

An observational one-stage prospective study of 44 patients with viral (B, C, B + C), alcoholic and mixed (alcohol-viral) etiology with an assessment of the final hard point - the onset of a fatal outcome from CP or its complications was carried out. The age of patients from 27 to 72 years (M ± m = 49 ± 8.5 years), 26 men and 18 women.

The moment of inclusion in the study - verification in the hospital of the CPU or admission to the hospital in connection with the decompensation of the CPU. The diagnosis of CP was confirmed morphologically (by biopsy) in 12 patients, in the rest - on the basis of the presence of signs of diffuse damage to the liver, the presence of hepatic cell deficiency syndrome, portal hypertension syndrome (varicose veins of the stomach and esophagus, ascites). The etiology of CP 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, HCV RNA) and D (a / t to HDV).

Patients with severe concomitant pathology were excluded from the study: chronic heart failure, rhythm disturbance, history of stroke, severe diabetes mellitus, oncopathology, tuberculosis, kidney diseases with renal failure, lung diseases with respiratory failure. The observation period ranged from 14 days to 6 months.

All patients with CP were divided into 2 groups (survivors - 1 g., Deceased - 2 g.) During the entire observation period, 14 patients died. The groups of deceased and surviving patients with CP were comparable by gender and age. The distribution of characters in the compared groups did not obey the laws of normal distribution, therefore, the comparability of groups by gender and age, as well as the comparison of indicators between groups was carried out using the non-parametric Mann-Whitney criterion.

Groups 1 and 2 were compared according to clinical data (ascites, encephalopathy, severity of asthenic, dyspeptic and hemorrhagic syndromes, as well as hepato- and splenomegaly), Doppler indices of hepatic hemodynamics.

Clinical and biochemical blood parameters of the groups are presented in table 1 - Clinical blood parameters of patients with cirrhosis of the liver of viral and alcoholic etiology and in table 2 - Biochemical blood parameters of patients with cirrhosis of the liver of viral and alcoholic etiologies.

As a result of assessing the clinical and biochemical parameters of the groups, it was revealed that independent factors of the poor prognosis are leukocytosis, anemia, thrombocytopenia, accelerated ESR, hyperbilirubinemia, increased ACT, ALT, GGTP, increased creatinine, and a decrease in IPT. Statistically significant unfavorable prognosis factors are shown in bold in Tables 1 and 2 and were considered as such at p <0.05.

When conducting a multilevel neurodynamic analysis of cardiac rhythmograms using the Omega-S PAK (manufacturer of MedKosmos-E LLC, Moscow, Russia), the results of indices A, B1, C1 and D1 were obtained, which are presented in Table 3 — Rhythmocardiographic parameters of patients cirrhosis of the liver of viral and alcoholic etiology. Indices A, B1, C1 and D1 were statistically significant.

Table 4 (The relationship of information indices with laboratory methods for examining patients with cirrhosis of the liver of viral and alcoholic etiology) presents the correlation dependence of information indices A, B1, C1 and D1 with these clinical and biochemical blood parameters.

Using the SPSS 13.0 computer program, using discriminant analysis, a discriminant function was created to predict a fatal outcome for six months in patients with cirrhosis of the liver of viral and alcoholic etiologies: Y _outcome = -2.217 + 0.031 * A + 0.064 * B1 + 0.012 * C1 + 0.025 * D1, where A, B1, C1, and D1 are indices obtained using multilevel neurodynamic analysis of cardiac rhythmograms.

All coefficients of the equations are significant (p <0.05), and the factors taken into account have a high contribution and account for 93.2% (R ² = 0.74) of the variation of the dependent variables, respectively.

Table 5 (Test for equality of group average values of the equation of fatal outcome in patients with cirrhosis of the liver of viral and alcoholic etiology) presents the test for equality of group average values used in the formula, where F is the F-criterion, p is significance. With the help of Lambda Wilks, a test was made for the significance of differences from each other the average values of the discriminant function in the groups: Lambda Wilks = 0.439, Chi - square - 32.9147, p <0.000005. When the value of Y _outcome <-0.41 predict death in patients with cirrhosis of the liver of viral and alcoholic etiology.

Thus, the distinctive essential features are new and increase, compared with the prototype, the accuracy of predicting the onset of death in patients with cirrhosis of the liver of viral and alcoholic etiology within 6 months after the examination.

We give examples of the clinical implementation of the method.

Example 1. Patient A., 54 years old, card No. 16595. 11/16/09

Complaints: general weakness, lethargy, heaviness in the right hypochondrium, swelling.

From the anamnesis: it is known that since April 2008, for the first time, it began to note heaviness in the right hypochondrium, an increase in the volume of the abdomen, severe weakness, nausea, and a decrease in body weight of 2.5-3 kg in 3 months; at the place of residence, the examination revealed: platelets - 62 * 10 ⁹ , hemoglobin - 134 g / l, HBsAg - positive, AntiHCV - negative. During biochemical examination: ALT - 328 units / l, ACT - 299 units / l, total bilirubin - 28 units / l. In 2008, according to ultrasound: diffuse densification of the liver, pancreas, splenomegaly, ascites, moderate portal hypertension (v. Porte - 14 mm). FGDS: gastroduodenitis. She was hospitalized in the city infectious diseases hospital named after S.P. Botkin. The condition is regarded as chronic viral hepatitis B, moderate activity, did not receive specific antiviral therapy, took hepatoprotectors: heptral, essler forte, enzymes - creon, diuretics, dufalac with a positive effect. Since January 2009, when examining in the clinic on FGDS: for the first time revealed varicose veins of the esophagus (esophageal hypertrophy of the esophagus 2nd degree), atrophic gastritis. Ultrasound of the abdominal cavity: moderate ascites, splenomegaly, diffuse changes in the liver and pancreas, expansion of the portal vein - v. porte - 14 mm. The condition is regarded as chronic viral hepatitis B, cirrhotic stage. Portal hypertension: BPV of the esophagus, hypersplenism. Edematous ascites syndrome. Upon examination, platelets - 41 * 10 ⁹ , hemoglobin - 139 g / l, ALT - 234 units / l, ACT - 218 units / l, total bilirubin - 28 units / l. She received courses - heptral, essentiale, duphalac, diuretics, during treatment, edematous ascites syndrome decreased. In October 2009, according to the FGDS: an esophageal hypertrophy of the esophagus was detected 3-4 degree, taking into account the high risk of bleeding - in 122 MSCs in October, the esophagus veins were doped. Deterioration over the past month, when patient A. began to notice again an increase in the abdomen in volume, general weakness increased.

Objectively: at the time of inspection - in the mind, oriented in time and space, answers the questions correctly, the nature of the handwriting is not changed.

The skin and visible mucous membranes of normal color, clean.

Pulse 68 beats per minute, rhythmic, satisfactory filling and tension. Blood pressure - 110/70 mm Hg With auscultation of the heart - tones are muffled, rhythmic. In the study of mild pathological changes were not detected. The abdomen is of the correct form, actively participates in the acts of breathing, during palpation is soft, painless, increased in volume due to ascites. Liver +6 cm from the edge of the costal arch. Spleen +1 cm from the edge of the costal arch. Rumbling is painless.

Clinical and laboratory analyzes during the treatment of patient A.: Hemoglobin level - 135 g / l, erythrocytes - 4.1 × 10 ¹² / l, white blood cells - 3.4 × 10 ⁹ / l, ESR - 20 mm / h, platelets - 42 × 10 ⁹ / L, ALT - 289 units / L, ACT - 323 units / L, alkaline phosphatase - 148 units / L, GGTP - 28 units / L, total bilirubin - 21 units / L, total protein - 68 g / l, albumin - 20 g / l, creatinine - 54 μmol / l, IPI 62%.

FGDS: Esophageal veins are not strained. Condition after ligation of the veins of the esophagus. Chronic gastroduodenitis, without exacerbation. At the time of examination, there were no signs of bleeding.

Ultrasound of the abdominal cavity: hepatosplenomegaly, v. porte 15 mm, ascites.

Hepatitis Markers:

HBsAg - Positive

Anti HCV - negative,

RW - negative,

Number Communication Test (TSC) - 37 s,

Test Line (TL) - 56 s,

The number of errors when executing a TL (CO _TL ) is 5.

According to psychometric testing, latent encephalopathy is determined.

Neurologist consultation: Neurological history is not burdened.

In neurological status - consciousness is clear, orientation of all types is preserved, speech is normal in pace, initiative in conversation, answers questions correctly, sometimes slowly, reluctantly. Elements of emotional lability. The nature of the handwriting is not changed. Fields of vision are not changed, mild anisocoria (pupils S = D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points are painless. Violations of smell, hearing - not detected. Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. It presents hyperesthesia with a hyperpathic hue in the type of "socks" from the level of the ankles. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - it is stable. There are no meningial symptoms.

Conclusion: at the time of examination, there is no data for acute neurological pathology. There is latent encephalopathy, more likely of hepatic origin.

EEG: No data were obtained for pathological activity, the α-rhythm is regular, correctly distributed, symmetrical, spindle-shaped, not distorted, without outbreaks of hypersynchronization with a frequency of 8.5-12 vibrations per 1 s, amplitude up to 80 μV, index 85%.

Single flash of light: α-rhythm depression is clear, simultaneous in all leads, restoration of the α-rhythm is within normal limits. Extinction of approximate reaction within normal limits.

Rhythmic photostimulation. The range of rhythm assimilation is 8-24 Hz. The assimilation of the rhythm is not higher than the background activity, long, symmetrical.

Trigger photostimulation does not cause pathological activity.

Conclusion: No pathological abnormalities were found.

Conclusion: Based on complaints, examination, and clinical and laboratory data, patient A. was diagnosed with:

Chronic viral hepatitis B, cirrhotic stage according to Child Pugh B.

Portal hypertension syndrome (BPH of the esophagus 3 degree, hypersplenism).

Esophageal vein ligation from October 2009

Ascites syndrome.

Chronic gastroduodenitis, without exacerbation.

Complication: Hepatic cell failure, class B,

hepatic encephalopathy latent stage.

Given the presence of ascitic syndrome in patient A., poorly corrected therapy, as well as thrombocytopenia, it was necessary to determine the prognosis of the course of the disease (the possibility of fatal outcome) for the next 6 months to solve family issues during the patient’s life and to prescribe expensive therapy. The prognosis of fatal outcome within 6 months of patient A. by the prototype method (according to the ACT indicators - 323 units / l, creatinine - 54 μmol / l), amounted to 63%, that is, the prognosis is poor.

When using multilevel neurodynamic analysis of cardiac rhythmograms using the Omega-S PAC, the following data were obtained:

Index A - 27%, Index B1 - 18%, Index C1 - 9%, Index D1 - 1%.

According to the claimed formula:

Y _outcome = -2.217 + 0.031 * A + 0.064 * B1 + 0.012 * C1 + 0.025 * D1

Y _outcome = -2.217 + 0.031 * 27 + 0.064 * 18 + 0.012 * 9 + 0.025 * 1 = -0.09

The resulting coefficient of -0.09 indicates a favorable prognosis.

Subsequently, the patient underwent pathogenetic palliative therapy. In the future, the prognosis was confirmed - the patient is still alive (2011). The forecast for the prototype method turned out to be false positive. Outpatient clinical and biochemical analyzes in February 2011: hemoglobin level - 125 g / l, erythrocytes - 3.5 × 10 ¹² / l, white blood cells - 3.3 × 10 ⁹ / l, ESR - 22 mm / h, platelets - 56 × 10 ⁹ / L, ALT - 143 units / L, ACT - 152 units / L, alkaline phosphatase - 186 units / L, GGTP - 27 units / L, total bilirubin - 27 units / L, total protein - 68 g / l, albumin - 23 g / l, creatinine - 64 μmol / l, IPI 63%.

Example 2. Patient K., 58 years old, card No. 16853. 11/19/09 Complaints: general weakness, heaviness in the right hypochondrium, edema. From the anamnesis: In 2003, for the first time, peeling of the skin began to be noted. Not examined, not treated. From September to December 2003, he noted a weight loss of 15 kg. Then weakness, weight loss, and pains in the epigastric region, not related to eating, gradually increased, and in March 2004 he was hospitalized by the ambulance in the Peter the Great Hospital (pavilion 24/4 - therapy department). On examination: HBsAg - positive, AntiHCV - negative. FGDS - erosion in the stomach, BPH - not detected. The condition is regarded as chronic viral hepatitis B. He received infusion and hepatoprotective therapy. Discharged with improvement. In 2006, he periodically noted pain in the right hypochondrium, was examined: according to the FGDS of the Esophagus Esophagus RV, the ultrasound of the abdominal cavity - diffuse changes in the liver, v. porte - 13 mm. Hepatitis B markers:

RNA HBV-DNA (+). A biochemical examination of ALT - 76 units / l, ACT - 64 units / l, total bilirubin - 26 units / l. The condition is regarded as chronic viral hepatitis B, cirrhotic stage (esophageal hypertrophy of the esophagus, hypersplenism), HBV-DNA RNA (+), received combination antiviral therapy (IFN-A) for 6 months with virologic remission and hepatoprotectors (heptral, phosphogliv) .

In August 2009, he began to notice an increase in the size of the abdomen, swelling of the legs.

He took triampur, furosemide with little effect. Markers of hepatitis B: RNA HBV-DNA (+), observed in an infectious disease specialist, took 0.5 grams of araklud, cycloferon 2 times a week according to the scheme, hepatoprotectors, diuretics, dufalac. He worked, disability - 3 group.

Over the past month, general weakness, lethargy gradually increased, the abdomen increased in volume, and therefore was hospitalized in the therapeutic department.

Objectively: at the time of inspection - in the mind, oriented in time and space, answers the questions correctly, in slow motion, the nature of the handwriting is changed.

The skin and visible mucous membranes of normal color, clean.

Pulse 65 beats per minute, rhythmic, satisfactory filling and tension. Blood pressure - 105/70 mm Hg

With auscultation of the heart - tones are muffled, rhythmic. In the study of mild pathological changes were not detected. The abdomen is of the correct form, actively participates in the acts of breathing, during palpation is soft, painless, increased in volume due to ascites. Liver +7 cm from the edge of the costal arch. Spleen +1 cm from the edge of the costal arch.

Rumbling is painless.

Clinical and laboratory tests during the treatment of patient K.:

The hemoglobin level is 117 g / l, erythrocytes - 3.27 × 10 ¹² / l, white blood cells - 4.4 × 10%, ESR - 51 mm / h, platelets - 72 × 10 ⁹ / l, ALT - 90 units / l, ACT - 116 units / l, alkaline phosphatase - 202 units / l, GGTP - 154 units / l, total bilirubin - 53 units / l, total protein - 67 g / l, albumin - 27 g / l creatinine - 83 μmol / L, IPI 65%.

FGDS: BPH of the esophagus 3 degrees. Chronic gastroduodenitis, without exacerbation. At the time of examination, there were no signs of bleeding. Ultrasound of the abdominal cavity: hepatosplenomegaly, v. porte 15 mm, ascites.

Hepatitis Markers:

HBsAg - Positive

Anti HCV - negative,

RW - negative,

Number Connection Test (TSC) - 50 s,

Test Line (TL) - 69 s.

The number of errors when performing a TL (CO _TL ) is 8.

According to psychometric testing, hepatic encephalopathy of the 1st degree of a clinically expressed stage is determined. Neurologist consultation: Neurological history is not burdened.

In the neurological status - the consciousness is clear, the orientation of all types is preserved, speech is normal in pace, not conversational in the conversation, he answers the questions correctly, slowly, reluctantly. Elements of emotional lability. The nature of the handwriting is changed. Fields of vision are not changed, mild anisocoria (pupils S = D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points are painless. Violations of smell, hearing - not detected. Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. It presents hyperesthesia with a hyperpathic hue in the type of "socks" from the level of the ankles. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - steady. There are no meningial symptoms.

Conclusion: at the time of examination, there is no data for acute neurological pathology. There is an encephalopathy of the 1st degree of a clinically pronounced stage, more likely of hepatic origin.

EEG: No data were obtained for pathological activity, the α-rhythm is regular, correctly distributed, symmetrical, spindle-shaped, not distorted, without outbreaks of hypersynchronization with a frequency of 9-11 oscillations per 1 s, amplitude up to 75 μV, index 83%.

Single flash of light: α-rhythm depression is clear, simultaneous in all leads, restoration of the α-rhythm is within normal limits. Extinction of approximate reaction within normal limits.

Rhythmic photostimulation: rhythm assimilation range of 8-24 Hz. The assimilation of the rhythm is not higher than the background activity, long, symmetrical.

Trigger photostimulation: does not cause pathological activity.

Conclusion: No pathological abnormalities were found.

Conclusion: Based on complaints, examination, and clinical and laboratory data, patient K. was diagnosed with:

Chronic viral hepatitis B, cirrhotic stage according to Child Pugh C.

Portal hypertension syndrome (BPH of the esophagus 3 degree, hypersplenism). Ascites syndrome.

Chronic gastroduodenitis, without exacerbation.

Chronic pancreatitis, without exacerbation.

Complication: Hepatic cell failure, class C, hepatic encephalopathy of the 1st degree of clinically expressed stage.

Given the presence of ascitic syndrome, thrombocytopenia, a high risk of bleeding in patient K., for further labor prognosis (patient K. had an open sick list), as well as the appointment of expensive therapy, it was necessary to determine the prognosis of the disease (the possibility of death) for the next 6 months .

The prognosis of fatal outcome within 6 months of patient K. according to the prototype method (according to ACT indicators - 116 units / l, creatinine - 83 μmol / l), amounted to 30.7%, that is, the prognosis is favorable, which allowed us to hope for the patient's survival in the coming period - 6 months.

When using multilevel neurodynamic analysis of cardiac rhythmograms using the Omega-S PAK, the following data were obtained:

Index A - 9%, Index B1 - 10%, Index C1 - 2%, Index D1 - 1%.

According to the claimed formula:

Y _outcome = -2.217 + 0.031 * A + 0.064 * B1 + 0.012 * C1 + 0.025 * D1

Y _outcome = -2.217 + 0.031 * 9 + 0.064 * 10 + 0.012 * 2 + 0.025 * 1 = -1.25

The resulting coefficient of -1.25 indicates an unfavorable prognosis.

Subsequently, the patient underwent pathogenetic palliative therapy. In December 2009, esophageal vein ligation was performed. In February 2010, patient K. developed a hepatic coma and patient K. died.

Example 3. Patient Sh., 53 years old, map No. 18897. 11/26/09

Complaints: general weakness, drowsiness, heaviness in the right hypochondrium, edema.

From the anamnesis: it is known that for 15 years alcohol abuse is about 500 ml per day, since April 2005 yellowness of the skin, darkening of urine, and a decrease in appetite appeared. It was treated on an outpatient basis - from honey. cards - HBsAg negative, AntiHCV - negative, abdominal ultrasound - hepatosplenomegaly; ACT - 196 units / L, ALT - 76 units / L, alkaline phosphatase - 231 units / L, GGTP - 298 units / L, took hepatoprotectors, heptral, Essential Forte N, Karsil. In 2008, a varicose vein (HRV) of the esophagus of the 2nd degree, ascites was revealed in the Alexander Hospital, he underwent treatment with hepatoprotectors, diuretic and detoxification therapy. The condition is regarded: chronic toxic hepatitis (ASH), cirrhotic stage, portal hypertension (hypersplenism, grade 2 esophagus esophagus). After discharge, he periodically took hepatoprotectors (Karsil, Hofitol, Zdorovka). Continued to abuse alcohol - 200-300 ml per week. In 2009, an outpatient examination: ECG: 65 heart rate sinus, incomplete blockade of the right bundle branch, hepatitis markers B and C (HBsAg, AntiHCV) are negative. Over the past 2-3 weeks, tremor of the upper extremities, weakness, decreased appetite, and drowsiness in the daytime began to be noted.

Objectively: at the time of inspection - in the mind, oriented in time and space, answers the questions correctly, in slow motion, the nature of the handwriting is changed.

The skin and visible mucous membranes of icteric color, clean. Pulse 68 beats per minute, rhythmic, satisfactory filling and tension. Blood pressure - 100/65 mm Hg With auscultation of the heart - tones are muffled, rhythmic. In the study of mild pathological changes were not detected. The abdomen is of the correct form, actively participates in the acts of breathing, during palpation is soft, painless, increased in volume due to ascites. Liver +7 cm from the edge of the costal arch. Spleen +1 cm from the edge of the costal arch. Rumbling is painless.

Clinical and laboratory tests during the treatment of patient Sh .:

The hemoglobin level is 123 g / l, erythrocytes - 3.21 × 10 ¹² / l, white blood cells - 14.2 × 10 ⁹ / l, ESR - 48 mm / h, platelets - 130 × 10 ⁹ / l, ALT - 44 units ./l, ACT - 48 units / l, alkaline phosphatase - 200 units / l, GGTP - 94 units / l, total bilirubin - 224 units / l, total protein - 69 g / l, albumin - 24 g / l, creatinine - 45 μmol / l, IPT 45%.

FGDS: BPH of the esophagus 3 degrees. Chronic gastroduodenitis, without exacerbation. At the time of examination, there were no signs of bleeding. Ultrasound of the abdominal cavity: hepatosplenomegaly, v. porte 16 mm, ascites.

Hepatitis Markers:

HBsAg - negative

Anti HCV - negative,

RW - negative,

Number Connection Test (TSC) - 54 s,

Test Line (TL) - 89 s.

The number of errors when performing TL (KL _TL ) - 9

According to psychometric testing, hepatic encephalopathy of the 1st degree of a clinically expressed stage is determined.

Neurologist consultation: Neurological history is not burdened.

In neurological status - consciousness is clear, orientation of all types is preserved, speech is slow in pace, not conversational in conversation, answers questions correctly, slowly, monosyllables, reluctantly. Elements of emotional lability. The nature of the handwriting is changed. Fields of vision are not changed, anisocoria (pupils S <D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points - painless. Violations of smell, hearing - not detected. Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. It presents hyperesthesia with a hyperpathic hue in the type of "socks" from the level of the ankles. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - it is stable. There are no meningial symptoms.

Conclusion: at the time of examination, there is no data for acute neurological pathology. There is an encephalopathy of the 1st degree of a clinically pronounced stage, more likely of hepatic origin.

EEG: No data were obtained for pathological activity, the α-rhythm is irregular, with deformation, symmetrical, spindle-shaped, without outbreaks of hypersynchronization with a frequency of 7-8 vibrations per 1 s, amplitude up to 75 μV, index 80%.

Single flash of light: α-rhythm depression is clear, simultaneous in all leads, restoration of the α-rhythm is within normal limits. Extinction of approximate reaction within normal limits. Rhythmic photostimulation: rhythm assimilation range of 8-24 Hz. The assimilation of the rhythm is not higher than the background activity, long, symmetrical.

Trigger photostimulation: does not cause pathological activity.

Conclusion: No pathological deviations were detected, it is noted by deformation of the α-rhythm with a frequency of 7-8 vibrations in 1 s.

Conclusion: Based on complaints, examination and clinical and laboratory data, patient Sh. Has chronic toxic hepatitis (ASH), cirrhotic stage of Child Pugh C.

Portal hypertension (hypersplenism, BPV of the esophagus, grade 3).

Edematous ascites syndrome.

Chronic gastroduodenitis, without exacerbation.

Chronic pancreatitis, without exacerbation.

Complication: hepatic cell failure, class C, hepatic encephalopathy of the first degree of a clinically pronounced stage.

Given the presence of ascitic syndrome, thrombocytopenia, and a high risk of bleeding in patient Sh., In order to prescribe expensive therapy, it was necessary to determine the prognosis of the course of the disease (the possibility of death) for the next 6 months.

The prognosis of fatal outcome within 6 months of patient III, according to the prototype method (according to ACT indicators - 48 units / l, creatinine - 45 μmol / l), amounted to 11.5%, that is, the prognosis is favorable, which allowed us to hope for the patient's survival in the coming period - 6 months.

When using multilevel neurodynamic analysis of cardiac rhythmograms using the Omega-S PAC, the following data were obtained:

Index A - 5%, Index B1 - 15%, Index C1 - 1%, Index D1 - 1%. According to the claimed formula:

Y _outcome = - 2.217 + 0.031 * A + 0.064 * B1 + 0.012 * C1 + 0.025 * D1

Y _outcome = - 2.217 + 0.031 * 5 + 0.064 * 15 + 0.012 * 1 + 0.025 * 1 = -1.06

The resulting coefficient of -1.06 indicates an unfavorable prognosis.

Subsequently, the patient underwent pathogenetic palliative therapy. In February 2010, patient Sh. Developed hepatic coma and patient Sh. Died.

The accuracy of predicting the onset of death in patients with cirrhosis of the liver of viral and alcoholic etiology by the present method is 93.2%. Of 44 patients with CP in 41 patients, the prognosis was confirmed - in 30 patients the prognosis was favorable, in 11 - unfavorable. The error is 3 people (6.8%), that is, a favorable prognosis did not materialize.

According to the prototype method, the accuracy of predicting the onset of death in patients with cirrhosis of the liver of viral and alcoholic etiology is 84.1%. Of the 44 patients with CP in 37 patients, the prognosis was confirmed - in 29 patients the prognosis was favorable, in 8 - poor. The error was 7 people (15.9%), that is, an unfavorable prognosis in 1 person was not confirmed, and a favorable prognosis did not materialize in 6 people.

Thus, the inventive method for the diagnosis of predicting the onset of death in patients with cirrhosis of the liver of viral and alcoholic etiology increases the accuracy of diagnosis by 9.1% compared with the method we have chosen as a prototype.

Table 1 Clinical indicators of blood of patients with cirrhosis of the liver of viral and alcoholic etiology Indicators Survived, N = 30 Died, N = 14 R Нb, g / l 116.0 ± 2.47 94.4 ± 4.10 <0.05 Er, × 10 ¹² / l 3.40 ± 0.10 2.8 ± 0.13 <0.01 Tr, × 10 ⁹ / L 127.2 ± 12.50 83.4 ± 11.48 <0.05 L × 10 ⁹ / L 4.7 ± 0.48 8.3 ± 0.89 <0.01 ESR, mm / h 28.3 ± 3.12 47.3 ± 4.15 <0.01

table 2 Biochemical blood parameters of patients with cirrhosis of the liver of viral and alcoholic etiology Indicators Survived, N = 30 Died, N = 14 R Total protein, g / l 70.4 ± 1.71 70.0 ± 1.42 > 0.05 Albumin, g / l 26.8 ± 1.31 25.4 ± 1.23 > 0.05 ACT, units / l 91.3 ± 14.51 194.8 ± 16.12 <0.005 ALT, units / l 73.5 ± 14.55 125.0 ± 11.91 <0.05 Bilirubin total., Μmol / l 35.7 ± 3.74 89.4 ± 4.56 <0.05 Alkaline phosphatase, units / l 204.8 ± 13.56 221.5 ± 10.90 > 0.05 GGTP, units / l 67.2 ± 10.10 169.7 ± 9.41 <0.001 Creatinine, μmol / L 62.0 ± 2.75 105.2 ± 5.49 <0,0005 PTI,% 68.4 ± 2.11 53.1 ± 2.41 <0.05

Table 3 Rhythmocardiographic parameters of patients with cirrhosis of the liver of viral and alcoholic etiology indices Survived, N = 30 Died, N = 14 R BUT 38.9 ± 3.60 7.9 ± 1.71 <0.00001 IN 1 22.0 ± 1.76 5.2 ± 1.52 <0.00001 C1 13.2 ± 1.90 0.8 ± 0.21 <0.0001 D1 8.6 ± 2.47 0.5 ± 0.20 <0.05

Table 4 The relationship of information indices with indicators of laboratory methods for examining patients with cirrhosis of the liver of viral and alcoholic etiology Options INDEX BUT IN 1 C1 D1 ACT -0.34 * -0.36 * -0.32 * -0.20 * GGTP -0.38 * -0.46 ** creatinine -0.35 * -0.45 ** red blood cells 0.41 * ESR -0.38 * * p <0.05
** - p <0.01

Table 5 The test of equality of group average values of the death equation in patients with cirrhosis of the liver of viral and alcoholic etiology indices Lambda wilks F R BUT 0.563 32,555 <0.00001 IN 1 0.537 36,203 <0.00001 C1 0.686 19,193 <0.00001 D1 0.894 4,997 <0.05

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Claims (1)

A method for predicting a fatal outcome in patients with cirrhosis of the liver of viral or alcoholic etiology, characterized in that a multilevel neurodynamic analysis of cardiac rhythmograms is performed using a rhythmocardiograph and the Omega-S software and hardware complex, and the following indices are determined that reflect: “A” is the conjugacy of all, but mainly peripheral rhythmic processes, “B1” - the degree of balance of sympathetic and parasympathetic influences on the sinus node of the heart, “C1” - the state of the central subcortical p egulation, “D1” - the state of central cortical regulation, with subsequent calculation of the onset of death in patients with cirrhosis of the liver of viral or alcoholic etiology according to the formula: _Outcome = -2.217 + 0.031 · A + 0.064 · B1 + 0.012 · C1 + 0.025 · D1 and at a value of less than -0.41 predict _{the outcome of} death in these patients within 6 months after the test.