M. Abrahamovych, M. Farmaha

Danylo Halytsky Lviv National Medical University

Introduction. Comorbidity occupies the prominent place among the problems of modern medicine. The methods of treatment are not always effective even due to the fact that the population is getting older, and the chronic diseases are accumulated.

Liver diseases are not an exception. They can not be considered separately from the diseases of other organs and systems. Syntropic comorbid lesions not only complicate the disease course, but also determine the treatment and prognosis of the patients [1]. The disorders of the circulatory system, which occur in 70.0-90.0% of patients with LC among the syntropic comorbid lesions of liver cirrhosis (LC) – the final stage of chronic diffuse liver disease – are ones of the most common [1, 3, 4].

It is known that the syntropic disorders of the circulatory system in patients with LC cover two separate nosologies – cardiomyopathy (CMP) with characteristic changes in the structure and function of the heart and stable arterial hypotension with its peculiarities of daily rhythm and variability of blood pressure, the diagnosis of which requires the special examinations: echocardiogram with doppler exposure, daily blood pressure monitoring, etc. [5].

The purpose of the study. Because the special diagnostic methods are not always available to the primary care physician, to distinguish among the results of the examination of patients with LC under these conditions the clinical markers of syntropic comorbid lesions of the liver – CMP and stable arterial hypotension, which would allow the patient to be referred to the appropriate risk group and referral to follow up.

Materials and methods. After obtaining the written consent for a comprehensive survey in accordance with the principles of the Declaration of Helsinki, Convention on Human Rights and Biomedicine of the Council of Europe and the relevant laws of Ukraine, randomly, with the preliminary stratification on the presence of LC, 603 patients (445 men (73.8%) and 158 women (26.2%) aged 19-80 years (average age 49.2 ± 10.6 years)) who were treated in 2012-2015 in the Lviv Regional Hepatology Center, established on the basis of the Department of Internal Medicine №1 of Danylo Halytsky Lviv National Medical University and Gastroenterological Department of the Lviv Regional Clinical Hospital were included into the study.

Patients were provided with the comprehensive clinical, laboratory and instrumental examination of all organs and systems prior to treatment in accordance with the orders of the Ministry of Health of Ukraine dated 13.06.2005 No. 271 “On Approval of the Protocols of Medical Care Provision on the Specialty “Gastroenterology”, N 436 dated 03.07.2006. “On Approval of the Protocols of Medical Care Provision on the Specialty “Cardiology”.

Among the examined 603 cirrhotic patients, 490 (81.3%) patients with LC were diagnosed with extrahepatic blood circulatory system lesions (experimental group (EG)), were divided into three subgroups: with the presence of only syntropic CMP (103 patients) – EG A, only syntropic arterial hypotension (89 patients) – EG B, others (306 patients)), and 113 patients (18.7%) who had no circulatory system disorders (comparison group (CG)).

The study is devoted to the statistical analysis with the calculation of chances to put the correct diagnosis of the syntropic lesions of organs of the circulatory system, using the separate indicator – a marker that can be detected during the initial examination of the patient. The true probability of the diagnosis was determined using diagnostic value indicators: sensitivity, specificity and accuracy. Sensitivity (true positive proportion) is the indicator of medical statistics that reflects the proportion of positive results that correctly identify the ill subject as a patient, specificity (a truly negative proportion) is an indicator that provides the information about the proportion of negative results that correctly determine a healthy subject as such, and accuracy – the proportion of correctly delivered diagnoses based on information about the positive or negative result [2]. On the basis of these indicators, the odds ratio is defined as the number indicating that the absence or presence of the certain result is associated with the presence or absence of the particular disease in the statistical stratum, and the association (or contingency) coefficient, which characterizes how close the stochastic connection between the qualitative features – alternatives random variables is [2]. The study was carried out in four consecutive steps, which included the assessment of demographic information, patients’ complaints, history information, and results of the objective examination.

The actual material was processed on the personal computer in MS Excel and SPSS based on the conjugation tables with the diagnostic value indices calculation. The relationship between the CMP (or arterial hypotension) and the indicator tested was considered to be confirmed if the modulus of the association coefficient exceeded by 0.5 (or 0.3 for the contingency coefficient).

Results and discussion. The first step was to analyze the information from the patient’s passport, namely his gender and age. As we can see from table 1, in EG A there were 69 men and 34 women, in EG B – 68 and 21, in CG – 86 and 27, respectively. The sensitivity of the indicator (male affiliation) to the diagnosis of CMP, that means that the number of men with CMP is 66.99%, and with arterial hypotension – 76.40%. The specificity of the indicator reflecting the number of women without CMP or arterial hypotension is 23.76 and 28.24% respectively. Accuracy, namely belonging to male or female gender, in 38,36% of cases, allows to predict the presence of CMP, in 42,30% of cases – arterial hypotonia correctly. Among the men, CMP is less common and the arterial hypotension is 1.27 times more likely to be among men than women. However, there is no statistically verified association between the marker and the syntropic lesions of the circulatory system: between the marker and the CMP – unconfirmed inverse relationship (association coefficient – -0.23) and between the marker and arterial hypotension – unconfirmed direct relation (association coefficient – 0.12).

At the time of the review, there were 3 young patients (18-29 years old), 6 mature patients (30-44 years old), 90 patients of middle age (45-59 years old) and 4 elderly patients (60-74 years old) in EG A. There were 7 patients of young age, 49 of mature, 24 of middle and 9 of elderly in EG B. There were 13 patients of young age, 32 – of mature, 59 – of middle and 9 – of elderly in CG. In patients with CMP, the sensitivity of the indicator (patient of middle or elderly age) is 91.26%, the specificity is 50.00%, and the accuracy is 63.93%. Consequently, among the middle-aged or elderly patients, CMP is 10.44 times more widespread than among young or mature patients. According to the performed calculations, the confirmed direct relationship was recorded between the age of patients and the CMP (association factor – 0.83). In patients with arterial hypotension, the sensitivity of the marker (young or mature age) is 62.92%, the specificity – 75.00%, and accuracy – 71.48%. This indicates that among young or mature patients, arterial hypotension is 5.09 times higher than among the middle-aged or elderly patients. We found the direct relationship between age of patients and the presence of the arterial hypotension.

Consequently, the results of the study confirm that the patient’s gender does not provide the information on the presence of a syntropic disorder of the circulatory system, in contrast to age, which can reliably indicate the CMP (middle and advanced age) or arterial hypotension (young and mature age), that can be used as one of the statistically significant markers of the syntopic cardiovascular disease in patients with LC.

The second step of the study was to study the complaints of patients with LC and to identify those that can be used as markers of syntropic disorders of the circulatory system (table 2). All the patients of EG A have complaints of pain and/or feeling heaviness in the right hypochondrium. In EG B, pain and/or such heaviness were recorded in 81 patients, as well as in 99 patients of the CG. The sensitivity of the indicator as the marker of CMP is 100.00%, but as the marker of arterial hypotension – 91.01%, specificity – 8.63 and 4.27%, and the accuracy – 40.00 and 30.00%, respectively. We have noted that pain and/or heaviness in the right hypochondrium were less common among the patients with arterial hypotension than among the patients without it. However, the confirmed relationship between the indicator and the presence of CMP or arterial hypotension was detected. There is statistically unconfirmed direct relation between the indicator and the CMP (the coefficient of contingency was 0.18), and statistically unconfirmed inverse relationship (association coefficient was -0.38) between the presence of pain syndrome and arterial hypotension were found.

Complaints of pain and/or heaviness in the left hypochondrium were documented in 12 patients from EG A, 56 in patients from EG B and 41 from CG. The sensitivity of the indicator for the diagnosis of CMP reaches 11.65%, and for the diagnosis of arterial hypotension – 62.92%, the specificity is 51.98% and 75.46% respectively, the accuracy is 38.36% and 71.80% respectively. These complaints are less common in patients with CMP than in non-CMP patients and in 5.22 times more often can be observed in the patients with arterial hypotension than without it. Consequently, the confirmed inverse relationship between the marker and the CMP (association coefficient – -0.75) and confirmed direct relationship between the marker and arterial hypotension (association factor – 0.68) were found.

Nausea was documented in all the patients of EG A, in about 4/5 of the patients of EG B (71) and CG (94). The sensitivity of the marker is 100.00% for detecting CMP and 79.78% for the detection of arterial hypotension, the specificity is 15.38 and 5.74% and the accuracy is 44.63 and 27.85% respectively. Nausea is less common among the patients with arterial hypotonia than without it. The received information indicates that there is no connection between the presence of nausea and CMP (contiguous coefficient – 0.24) and the confirmed inverse relationship between nausea and arterial hypotension (association coefficient -0.61).

In the patients of EG A, 14 patients complained of abdominal distension, in the EG B – there were 19 such patients, in the CG – 17. The sensitivity of the marker for the diagnosis of CMP is 13.59%, for the detection of arterial hypotension – 21.35%, specificity – 82.18% and 85.65% respectively, accuracy – 59.02% and 66.89% respectively. Although complaints of abdominal distension are less common among the patients with CMP than without it and 1.62 times more often among the patients with arterial hypotension than without it, there is no statistically significant association between the marker and the syntropic lesions of the organs of the circulatory system: with CMP – unconfirmed inverse relationship (association coefficient – -0.16), with arterial hypotension – unconfirmed direct relationship (association coefficient – 0.24).

The periodic vomiting was observed in 19 patients of the EG A, 21 – of the EG B and 26 – of the CG. Sensitivity as the marker of CMP is 18.44%, but as the marker of arterial hypotension – 23.60%, specificity is 84.59% and 79.17%, accuracy is 67.89% and 62.95% respectively. Periodic vomiting occurs 1.24 times more often in patients with CMP than without it, and 1.17 times more often in patients with arterial hypotension than without it. There was no statistically significant association between the marker and the syntropic diseases of the cardiovascular system in the patients with LC: between the marker and the CMP –  unconfirmed direct relationship (association factor – 0.11) and between the marker and arterial hypotension – also the unconfirmed direct relationship (association coefficient – 0.08).

Constipation was observed in 19 patients of the EG A, 32 – of the EG B and 18 – of the CG. The sensitivity of the complaint concerning the diagnosis of CMP is 16.50%, while concerning the diagnosis of arterial hypotension – 35.95%, the specificity is 75.25% and 83.80%, respectively, the accuracy is 55.41% and 69.83% respectively. Constipation is less common in patients with CMP than in patients without it, and is 2.90 times more often in patients with arterial hypotension than without it. But the reliably confirmed relationship between the marker and the CMP (unconfirmed inverse relationship, association coefficient – 0.25), and between the marker and arterial hypotension (unconfirmed direct relationship, association coefficient – 0.49) was not found.

The liquid, unformed excrements were observed in 20 patients from the EG A, in 18 patients from tgheEG B and in the same number of patients from the CG. The sensitivity of the complaint as the marker of CMP is 19.42%, but as the marker of arterial hypotension – 20.22%, specificity – 82.18% and 82.41% respectively, accuracy is 60.98% and 64.26% respectively. Unformed feces were 1.11 times more common in patients with CMP than without CMP, and 1.19 times more often in patients with arterial hypotension than without it. However, between the indicator and the syntropic lesions of the cardiovascular system, there was no relationship detected: with the CMP – unconfirmed direct relationship (association coefficient – 0.05), with arterial hypotension (association coefficient – 0.09).

There were no complaints of joint pain in the patients of the EG A, as opposed to the EG B and the CG, where, 7 and 9 patients expressed such complaints respectively. The sensitivity of the diagnostic index concerning CMP is 0.00%, and the sensitivity for the detecting of the arterial hypotension is 7.00%. The specificity of the indicator is 91.88 and 95.73% respectively, the accuracy is 60.33 and 69.67%, respectively. Hence, complaints of joint pain are 1.92 times more common among the patients with the arterial hypotension than among the patients without it. However, it was found the unconfirmed inverse relationship between arthralgia and CMP (contiguous factor – 0.17) and the unconfirmed direct relationship between arthralgia and arterial hypotension (association coefficient – 0.31).

Complaints of bone pain were detected in four patients of the EG A, in five – of the EG B, and in five – of the CG patients. The sensitivity of the indicator for the diagnosis of CMP is 3.88%, for the diagnosis of arterial hypotension – 5.62%, the specificity is 95.05% and 95.83% respectively, the accuracy is 64.26% and 69.51% respectively. Ossalgias are less common in patients with CMP than without it, and 1.37 times more common among the patients with arterial hypotension than without it.

However, there is no reliable relationship between the indicator and the syntropic lesions of the organs of the circulatory system: between the ossalgia and the CMP there is unconfirmed inverse relationship (the association coefficient is -0.13), and between the ossalgia and the arterial hypotonia – unconfirmed direct relation (association coefficient – 0.16).

Patients with LC often complained about pain in the muscles: 58 patients – from the EG A, 41 – from the EG B, 53 – from the CP. The sensitivity of myalgia as the marker of CMP is 56.31%, but as the marker of arterial hypotension – 46.07%, specificity – 63.47% and 48.61% respectively, accuracy is 54.43% and 47.87% respectively. Migraines were reported 1.48 times more frequently among the patients with CMP than without it, and less frequently among the patients with arterial hypotension than without it. There is the unconfirmed direct relationship between the marker and the CMP (association factor – 0.19), and the unconfirmed inverse relationship (association coefficient -0.11) between the marker and arterial hypotension.

Complaints of constant sensation of tingling, tickling, burning of the skin without apparent defects, were observed in 75 patients of the EG A, in 73 – of the EG B and in 57 – of the CG. The sensitivity of paresthesia concerning the diagnosis of CMP reaches 72.82%, while concerning the diagnosis of arterial hypotension – 82.02%, the specificity is 35.64 and 38.89% respectively, the accuracy is 48.20 and 51.48% respectively. Paresthesia was recorded 1.48 times more frequently among the patients with CMP than without it, 2.90 times more often among the patients with arterial hypotension than without it. The unconfirmed direct relationship between the indicator and the CMP (association coefficient – 0.19) and between the indicator and arterial hypotension (association coefficient – 0.49) were found.

Complaints of general weakness and fatigue were recorded in all the patients from EG A and B and in 107 patients from the CG. The sensitivity of the indicator for detecting the CMP as well as arterial hypotension reaches 100.00%, the specificity is 0.51 and 0.47% respectively, and the accuracy is 34.67% and 30.00% respectively. There is the unconfirmed direct relationship between the index and the CMP (contiguous coefficient – 0.04), as well as between the index and the arterial hypotension (contiguous coefficient – 0.04).

Consequently, due to the large number of complaints of the cirrhotic patients for the diagnosis of syntropic lesions of the circulatory system, it is advisable to take into account only complaints of pain and/or heaviness in the left hypochondrium and nausea. The pain in the left hypochondrium denies the diagnosis of the CMP and indicates the presence of arterial hypotension. Nausea is the reliable evidence of the absence of stable arterial hypotension in the patient.

The third step was to identify the markers from information gathered during the anamnesis collection. The results of the study are presented in table. 3. For the duration of the liver disease (from the appearance of the first complaints to the objective examination moment), we conditionally divided the cirrhotic patients into two groups: those who are ill for three years or less, and those who are ill for more than three years. Among the patients of EG A there were 36 patients with LC for three years or less, 67 – with the history of more than three years, in EG B – there were 12 and 77, in CG – 90 and 23 such patients, respectively. The sensitivity of the marker (the duration of the LC for more than three years) concerning the detection of CMP is 65.05%, and concerning the detection of arterial hypotension – 86.52%, the specificity is 50.50 and 58.33%, respectively, the accuracy is 55.41 and 66.56 % respectively Among the patients with CMP, LC lasting more than three years is 1.90 times more frequent than among non-CMP patients, and among patients with arterial hypotension – 8.98 times more frequent than among the patients without it. There is no reliable relationship between the presence of CMP and the duration of the LC (unconfirmed direct relationship, association coefficient – 0.31), between the arterial hypotension and the marker there is a direct confirmed connection (association coefficient – 0.80).

Bleeding from the varicose veins of the esophagus in the history of patients with CMP were not detected, whereas in patients with stable arterial hypotension 31 such cases have been reported. In the history of 9 patients of the CG, bleeding from the varicose veins of the esophagus were detected in the past. The sensitivity of the indicator for the diagnosis of CMP is 0.00%, for the diagnosis of arterial hypotension – 34.83%, the specificity is 80.20 and 95.83%, respectively, the accuracy is 53.11 and 78.03% respectively. The bleeding in the history of patients with stable arterial hypotonia was in 12.29 times higher than in patients without it. The unconfirmed inverse relationship was detected between the CMP and the marker (contiguous coefficient – 0.28), and the confirmed direct relationship between the arterial hypotension and the marker (association coefficient – 0.85).

Depending on the etiological factor of the LC, we isolated monoethiologic LC (due to the toxic effects of alcohol, medicines, hepatitis B or C virus, autoimmune), polyethyologic connected (the influence of hepatitis B and C viruses) and polyethylobic combined (the effect of alcohol and hepatitis B virus or alcohol and virus hepatitis C). Other variants of the LC etiologies among the patients we surveyed were not noted. Among the patients of the EG A there were 69 cases of LC, caused by the influence of alcohol only, in the EG B there were 53 such cases, and in the CG – 65. The sensitivity of the marker for the correct diagnosis of CMP is 66.99%, arterial hypotension – 59.55%, specificity – 41.58 and 37.96% respectively, the accuracy is 50.16 and 44.26% respectively. Among the patients with CMP, there were found 1.45 times more patients with LC of alcoholic etiology than among non-CMP patients, and among the patients with arterial hypotension – less than in patients without arterial hypotension. However, no reliable relationship between the marker and cardiovascular complications was detected: unconfirmed direct relationship was established between the marker and the CMP (association coefficient – 0.18) and between the marker and arterial hypotension – unconfirmed inverse relationship (associative coefficient – -0.05).

Among the patients of the EG A, there were no patients with LC caused by hepatitis B virus, among the patients of the EG B there were seven such patients and in the CG – also seven. Sensitivity of such etiologic factor as CMP marker is 0.00%, as marker of arterial hypotension – 7.87%, specificity is 95.05 and 98.61% respectively, accuracy is 62.95 and 72.13%, respectively. Patients with stable arterial hypotension are 6.06 times more likely to be detected with the LC, caused by hepatitis B virus alone, than in patients without arterial hypotension. The unconfirmed inverse relationship between the etiologic factor and the presence of CMP (contiguity coefficient – 0.13) and the direct association (association coefficient – 0.72) between it and the presence of arterial hypotension were found.

Among the patients of EG A, there was one patient with LC caused by the influence of the hepatitis C virus. There were 3 such patients in the EG B, and 10 in the CG. Sensitivity of the marker for the CMP detection is 0.97%, for arterial hypotension – 3.37%, the specificity – 93.56 and 95.35% respectively, and the accuracy – 62.30 and 68.42% respectively. The LC caused by the hepatitis C virus is less common in patients with the CMP than in patients without it, the same as among the patients with arterial hypotension compared with the patients without it. The confirmed inverse relationship between the CMP and the LC of the hepatitis C-viral etiology (association coefficient – 0.75) and unconfirmed inverse relationship between the arterial hypotension and LC caused by hepatitis C virus (association factor – -0.17) was found.

In the EG A there were no patients with LC of autoimmune etiology, in the EG B – one such patient, in the CG – four patients. The sensitivity concerning the CMP detection is 0.00%, concerning the arterial hypotension – 1.12%, the specificity is 97.52% and 98.15% respectively, the accuracy is 64.59% and 69.84% respectively. Autoimmune LC is more common among the patients with arterial hypotension than in patients without it. However, no relationship was found between the index and the syntropic lesions of the circulatory system: the unconfirmed inverse relationship between the marker and the CMP (contiguity coefficient – -0.09), as well as between the marker and arterial hypotension (association coefficient – -0.25).

The LC resulting from the hepatotoxic effect of the medicines was diagnosed in one patient of the EG A and three patients of the CG. Among the patients of the EG B the patients with LC of the medication etiology were not found. The sensitivity of the marker for CMP diagnosis is 0.97%, for the arterial hypotension – 0.00%, the marker specificity is 99.01% and 98.61% respectively, the accuracy is 65.90% and 69.84% respectively. Among the patients with CMP, LC of medication etiology is less common than among the patients without it. However, there was no statistically verified association between the marker and the cardiovascular complications of the LC: there was the unconfirmed inverse relationship between the marker and the CMP (association factor – -0,01), as well as between the marker and arterial hypotension (contingency coefficient – -0.06 )

In the EG A there was one case of LC, due to the influence of hepatitis B and C viruses. In the EG B there were 9 such patients, in the CG – 7 patients. Sensitivity of the indicator for detecting the CMP is 0.97%, for the stable arterial hypotension – 10.11%, specificity – 92.08 and 96.30% respectively, the accuracy – 61.31 and 71.15% respectively. Consequently, among the patients with the CMP, LC, caused by the hepatitis B and C viruses, was much less frequent than among the patients without the CMP, and among the patients with arterial hypotension, these etiologic factors of the LC were found to be at 2.93 times more often than among the patients without arterial hypotension. The confirmed inverse relationship between the CMP and the marker (association factor – -0.80) and the unconfirmed direct relationship between the arterial hypotension and the marker (association factor – 0.49) were found.

The LC, caused by the combined effect of alcohol and hepatitis B virus, was detected in 27 patients from the EG A, 10 from the EG B and 12 from the CG.

The LC, caused by the influence of alcohol and the hepatitis C virus, was detected in 4 patients from the EG A, in 6  – from the EG B and 10 – from the CG. Sensitivity of the indicator as the marker of the CMP is 3.88%, arterial hypotension – 6.74%, specificity is 92.08% and 93.52% respectively, accuracy – 62.30% and 68.20% respectively. The LC of this etiology is less common in patients with or without the CMP, and in almost the same number of patients with and without arterial hypotension. The unconfirmed inverse relationship was detected between the marker and the presence of the CMP (association coefficient – -0.36), and the unconfirmed direct relationship between the marker and the arterial hypotonia (association coefficient – 0.02).

Consequently, due to the analysis of information from the history of patients with LC, it has been found that the presence of LC of hepatitis C-viral etiology or combined hepatitis B- and C-viral etiology in patients can reliably deny the diagnosis of the CMP, and the presence of LC lasting for more than three years, bleeding from varicose veins and/or the presence of hepatitis B viral etiology of LC, independently of each other, can reliably indicate that the patient has syntropic stable arterial hypotension.

The fourth step of the study was to analyze the information obtained during the initial objective examination of the patient (table 4). The body mass index (BMI), calculated using A. Kettle’s formula, was found to be lower than 25 in 80 patients of the EG A, 42 patients of the EG B, 64 patients of the CG. The sensitivity of normal or decreased BMI as the marker of the CMP is 77.67%, as the marker of arterial hypotension – 47.19%, specificity is 47.52 and 33.33% respectively, accuracy – 57.70% and 37.38% accordingly. Thus, among the patients with the decreased and normal BMI, arterial hypotension is 3.15 times more prevalent than among the patients with high BMI, and CMP is less common. Thus, the confirmed direct relationship between the presence of normal or decreased BMI and CMP (association coefficient – 0.52), as well as the unconfirmed inverse relationship between the BMI and arterial hypotension (association coefficient – -0.38) was found.

Jaundice of the skin was seen in all the patients of the EG A, in 56 patients of the EG B and in 51 patients of the CG. The sensitivity of the indicator for the diagnosis of the CMP is 100.00%, for the arterial hypotension diagnosis – 62.92%, the specificity is 45.69% and 27.01% respectively, the accuracy – 64.33% and 37.67% respectively. According to the information received, jaundice is less common among the patients with the stable arterial hypotension than among the patients without it. There is the confirmed direct correlation between the CMP and the jaundice of the skin (contingency coefficient – 0.47), and unconfirmed inverse relationship between the stable arterial hypotension and jaundice (association coefficient – -0.23).

The jaundice of the sclera was observed in all the patients of the EG A, in 60 patients from the EG B and in 60 patients from CG. The sensitivity of the marker to confirm the diagnosis of CMP is 100.00%, and to confirm the diagnosis of arterial hypotension – 67.42%, the specificity is 40.59 and 24.54% respectively, the accuracy is 60.66 and 37.05% respectively. Consequently, jaundice is less common among the patients with LC, complicated by the stable arterial hypotension, than among the patients without this complication. The verified direct relationship between the marker and the CMP (contingency coefficient – 0.43) and the unconfirmed inverse relationship between the marker and the stable arterial hypotension (contingency factor – -0.20) were found.

The bluish color of the skin of the nasolabic triangle was found in 25 patients of the EG A, 21 patients of the EG B and 11 – from the CG. Sensitivity of acrocyanosis as the marker of CMP is 24.27%, but as a marker of stable arterial hypotension – 23.60%, specificity – 84.16 and 83.33% respectively, accuracy is 63.93% and 65.90% respectively. Consequently, acrocyanosis occurs 1.70 times more frequently among the patients with CMP than among the patients without it, and 1.54 times more often among patients with stable arterial hypotension than without it. However, we did not find the statistically significant association between the marker and the CMP (unconfirmed direct relationship, association coefficient – 0.26) and between the marker and the stable arterial hypotension (unconfirmed direct relationship, association coefficient – 0.21).

In 27 patients from the EG A, xanthomas and xanthelases were recorded. The same changes were found on the skin of 33 patients from the EG B and 24 patients of the CG. Thus, the sensitivity of the indicator is 26.21% for the diagnosis of CMP, and 37.08% for the diagnosis of arterial hypotension, the specificity is 71.07 and 75.83% respectively, the accuracy is 55.67% and 64.33% respectively. Xanthomas and xanthelasms are less common among the patients with CMP than in patients without CMP, and 1.85 times more common among the patients with stable arterial hypotension than without it. However, there was no statistically significant association between the marker and the syntropic lesions of the circulatory system: between the marker and the CMP – the unconfirmed inverse relationship (association coefficient – -0,07), between the marker and arterial hypotension – the unconfirmed direct relation (association coefficient – 0.30).

Nearly one-third of the patients from EG A (30), 33 patients from the EG B were detected with hemorrhages. In the CG there were slightly fewer patients with the skin hemorrhages (20). The sensitivity of the indicator for the CMP detection is 29.13%, and for the detection of arterial hypotension – 37.08%, the specificity is 73.10 and 76.30%, respectively, the accuracy – 58.00% and 64.66%, respectively. Hence, hemorrhage is 1.12 times more common among the patients with the CMP than without it, and 1.90 times more among the patients with arterial hypotension than without it. But there is the unconfirmed direct relationship between the CMP and the indicator (association coefficient – 0.06), as well as between the arterial hypotension and the indicator (association coefficient – 0.31).

Teleangioectasias were detected in 68 patients from the EG A, in 76 patients from the EG B and 59 patients from CG. The sensitivity of the marker concerning the diagnosis of CMP is 66.19%, while concerning the diagnosis of arterial hypotension – 85.39%, the specificity is 33.17% and 41.20% respectively, the accuracy is 44.26% and 54.10% respectively. Teleangioectasias are less common in patients with CMP than among the non-CMP patients and in 4.10 times more common among the patients with stable arterial hypotension than without it. The unconfirmed inverse relationship between the indicator and the CMP was found (association coefficient – -0.02) and the direct correlation between the indicator and stable arterial hypotension (association coefficient – 0.61) was confirmed.

Symmetrical bright red palms in the area of ​​tenar, hypotenar and/or fingers were recorded in 27 patients from the EG A, in 22 patients from the EG B and in 23 patients from the CG. The sensitivity of palmar erythema, as marker of CMP, is 26.21%, but as the marker of stable arterial hypotension – 24.72%, specificity is 77.72% and 76.85% respectively, the accuracy is 60.33% and 61.64% respectively. Palmar erythema occurs 1.24 times more often among the patients with the CMP than without it, and 1.09 times more often in patients with stable arterial hypotension than without. However, there was no statistically significant association between the marker and the CMP (unconfirmed direct relationship, association coefficient – 0.11), as well as between the marker and the stable arterial hypotension (unconfirmed direct relationship, association coefficient – 0.04).

The body temperature above 37.0°C, was recorded in 25 patients of the EG A, in 21 patients of the EG B and in 10 patients of the CG. The sensitivity of hyperthermia as the indicator of CMP is 24.27%, as the indicator of arterial hypotension – 24.14%, specificity – 84.10 and 83.41%, respectively, accuracy – 63.42 and 66.11%, respectively. The elevated body temperature is 1.70 times more likely to occur in the CMP patients than in patients without it, and 1.60 times more often in the patients with the arterial hypotension than in patients without it. However, there is no statistically verified association between the hyperthermia and the CMP (unconfirmed direct relationship, association coefficient – 0.26) and between the hyperthermia and the arterial hypotension (unconfirmed direct relationship, association coefficient – 0.23).

In 14 patients from the EG A, 10 patients from the EG B and 13 patients from the CG , “raspberry” tongue was detected. The sensitivity of the indicator for detecting CMP is 13.59%, and for the stable arterial hypotensiondiagnosis – 11.24%, the specificity is 88.61% and 87.50% respectively, the accuracy is 63.29% and 65.25% respectively. Consequently, the “raspberry” tongue is 1.22 times more common in patients with CMP than in non-CMP patients, and rarer in patients with stable arterial hypotension than in patients without it. There is no statistically significant association between the marker and the syntropic complications of the circulatory system. There is the unconfirmed direct relationship between the marker and the CMP (association coefficient – 0.10), and the unconfirmed inverse relationship between the marker and the arterial hypotension (association coefficient – -0.06).

Ascites was detected in 35 patients from the EG A, in 82 patients from the EG B and in 38 patients from the CG. The sensitivity of ascites as the marker of the CMP is 33.98%, but as the marker of arterial hypotension – 92.13%, specificity is 39.09 and 65.40% respectively, accuracy is 37.33% and 73.33% respectively. Ascites is less common in patients with the CMP than in patients without it, and is 22.14 times more common among the patients with the arterial hypotension than in the patients without it. The proven inverse relationship was found between the ascites and the CMP (association coefficient – -0.50), and between the ascites and the arterial hypotension (association coefficient – 0.91).

Edema of the lower extremities was detected in 8 patients from the EG A, that is the lowest result among the experimental groups, in 52 patients from the EG B and in 31 patients from the CG. The sensitivity of the indicator for the diagnosis of CMP is 7.77%, for the arterial hypotension diagnosis – 58.42%, the specificity is 57.65% and 81.43% respectively, the accuracy – 40.47% and 74.58% respectively. Edema of the lower extremities is less common in the patients with CMP than without it, and is 6.16 times more common among the patients with the arterial hypotension than without it. The confirmed inverse relationship between the presence of edema and the CMP (association coefficient – -0.79) and the direct correlation between the presence of edema and the arterial hypotension (association factor 0.72) were confirmed.

The widened winding subcutaneous veins on the anterior abdominal wall were detected in 3 patients from the EG A, in 45 patients from the EG B and in 20 patients from the CG. The sensitivity of the presence of the “caput medusae” as the marker of the CMP is 2.91%, but as the marker of arterial hypotension – 50.56%, specificity is 67.34% and 89.20%, respectively, accuracy – 45.36% and 77.81% accordingly. Consequently, the widened winding subcutaneous veins of the anterior abdominal wall occur less frequently among the patients with the CMP than without it, and are 8.45 times more often among the patients with the arterial hypotension than without it. The confirmed inverse relationship between the presence of the “caput medusae” and the CMP (association coefficient – -0.88) and the direct correlation between the presence of the “caput medusae” and arterial hypotension (association coefficient – 0.79) were confirmed.

Increased liver’s sizes were detected in 76 patients from the EG A, in 86 patients EG B and in 54 patients from CG. The sensitivity of hepatomegaly as the marker of CMP is 73.79%, but as the marker of arterial hypotension – 96.62%, specificity – 30.69% and 39.81% respectively, accuracy – 45.25% and 56.39% respectively. Consequently, hepatomegaly is 1.25 times more common among the patients with the CMP than among the patients without the CMP and 18.96 times more common among the patients with arterial hypotension than among the patients without it. Therefore, there is no statistically verified association between the hepatomegaly and the CMP (association coefficient – 0.11) and there is the direct relationship between the presence of the hepatomegaly and the arterial hypotension (association coefficient – 0.90).

Increased spleen sizes were detected in 52 patients from the EG A, in 81 patients from the EG B and in 74 patients from the CG. The sensitivity of the splenomegaly as the marker of CMP is 55.91%, but as a marker of arterial hypotension – 91.01%, specificity is 21.72% and 37.62% respectively, accuracy – 32.65% and 53.95% respectively. Splenomegaly is less common in patients with the CMP than in the patients without it, and is 6.11 times more common in the patients with the arterial hypotension than without it. Thus, the unconfirmed inverse relationship was detected between the marker and the CMP (association coefficient – -0.48), the same as the direct confirmed association between the marker and the arterial hypotension (association coefficient – 0.72).

During the auscultation of the lungs, severe breathing was recorded in 19 patients from the EG A, in 37 patients from the EG B and in 43 patients from the CG. The sensitivity of the marker for the diagnosis of the CMP is 18.45%, for the arterial hypotension diagnosis – 41.57%, the specificity is 60.40 and 71.30% respectively, the accuracy is 46.23% and 62.62% respectively. Consequently, hard breathing is less characteristic for the patients with the CMP than for the patients without the CMP, and is 1.77 times more common in the patients with the stable arterial hypotension than without it. However, the statistically confirmed association was not detected either between the marker and the CMP (unconfirmed inverse relationship, association coefficient – -0.49), and between the marker and the arterial hypotonia (unconfirmed direct association, association coefficient – 0.28).

During the auscultation of the heart, 57 patients from the EG A, 17 patients from the EG B and 21 patients from the CG were recorded with the weakened heart tones. The sensitivity of the marker for detecting the CMP is 55.40%, concerning the diagnosis of arterial hypotension – 19.10%, specificity is 81.19 and 63.89% respectively, accuracy – 72.46% and 50.82% respectively. Consequently, attenuated tones are 5.35 times more likely to occur in the patients with the CMP than in non-CMP patients, and rarely in the patients with the arterial hypotension than without it. The confirmed direct relationship between the marker and the CMP (association coefficient – 0.68) and the unconfirmed inverse relationship between the marker and the arterial hypotension (associative coefficient – -0.41) were found.

The reduction in the daily urine output to 500.0 ml or less was recorded in 24 patients from the EG A, in 36 patients from the EG B and in 37 patientsfrom CG. The sensitivity of the indicator for the diagnosis of the CMP is 23.01%, and for the diagnosis of arterial hypotension – 40.45%, the specificity is 64.22% and 72.02%, respectively, the accuracy – 50.49% and 62.87% respectively. Oliguria is less common among the patients with the CMP than among the patients without CMP, and among the patients with arterial hypotension is 1.75 times more than among the patients without it. We did not find statistically significant correlations between the marker and the syntropic lesions of the cardiovascular system: with the CMP – the unconfirmed inverse relationship (association coefficient – -0.29), and with arterial hypotension – the unconfirmed direct relationship (association coefficient – 0.27).

According to the results, the normal or decreased BMI, icteric skin and sclera and weakened tones of the heart are associated with the CMP, and edema on the lower extremities, “caput medusae” – with its absence. Teleangioectasias, ascites, “caput medusae”, edema of the lower extremities, hepato- and splenomegaly indicate the presence of the stable arterial hypotension.

Conclusions. The analysis of the diagnostic value of the clinical markers of the circulatory system syntropic comorbid disorders in the cirrhotic patients makes it possible to state that in the presence of a patient of middle or elderly age with the complaints of pain and/or heaviness in the left hypochondrium, the absence of liver cirrhosis of hepatitis C- or C- and B-viral etiology, the presence of normal or decreased body mass index, jaundice of the skin and sclera, weakened heart tones in the absence of the “caput medusae” and edema of the lower extremities can be assumed to have cardiomyopathy, and in case of young or mature patients with the complaints of pain and/or heaviness in the left hypochondrium, nausea, liver cirrhosis duration for more than three years, the presence of the information on bleeding from the varicose veins of the esophagus in the patient’s history, cirrhosis of the liver of hepatitis B-viral etiology, telangioectasias, ascites, “caput medusae”, edema of the lower extremities, hepato- and splenomegaly – persistent arterial hypotension. Consideration of these clinical markers during the examination of the patients with liver cirrhosis will make it possible to form the risk groups regarding the presence of the corresponding syntropic comorbid disorders of the circulatory system, correctly examine a patient and determine the correct treatment tactics.

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