Method for predicting lingering clinical course of viral hepatitis in children

FIELD: medicine.

SUBSTANCE: method involves studying properties of deformability DP, erythrocytes aggregation EA, lipids micro-viscosity LMV in their membranes, changes in superficial erythrocyte cytoarchitectonics on diskocytes and degenerative prehemolytic forms number and, additionally, extrahepatic vascular marks. The properties under study are evaluated by means of forecasting coefficients FK, where FK=+5.2, if DP≤0.11 conditional units; FK=-3.5, if DP≥0.12 conditional units; if EA≤1.11 conditional units, FK=+1.0; if EA≥1.12 conditional units, FK=-5.6; if LMV≥4.5 conditional units, FK=+2.3; LMV≤4.4 conditional units, FK=-6.5; the number of diskocytes falling to 70% and lower, FK=+4.1; diskocytes value being ≥71%, FK=-2.6; irreversibly transformed prehemolytic forms number being IRPF≥13%, FK=+2.9; IRPF≤12%, FK=-2.0; increasing reversibly transformed erythrocytes number being RTE≥14%, FK=+2.5; RTE≤13%, FK=-2.3; extrahepatic vascular marks being observed during acute viral hepatitis period, FK=+8.8, no extrahepatic vascular marks being observed, FK=-5.0. The forecasting coefficients are summed up. The sum of FK≥+13, lingering clinical viral hepatitis course is to be predicted.

EFFECT: high accuracy of the method.

1 tbl

 

The invention relates to medicine, namely to infectious diseases.

It is now established that the mechanisms of managanese in viral hepatitis depends on the functional state of the microcirculation in the liver. Disturbance of microcirculation in the liver are one of the main causes of metabolic disorders that reduce the efficiency of the regeneration of liver cells and determining the severity and adverse outcomes of viral hepatitis (Sorenson S.N., Kazulin VE - Sat. the scientific. Tr. "Clinical aspects of disorders of microcirculation and blood rheology" Bitter, 1984; Nikiforov N, Ilyinsky Y.A - Ter. archive, 1989, T, No. 11; Vorob'ev VP - liver Disease and blood circulation. - M.: Knowledge, 1990; Luchshev VI, V. Zharov. - Epidemiology and infectious diseases, 1998, No. 5).

One of the leading mechanisms of microcirculation disorders are rheological disorders of erythrocytes (Cernoch A.M. Microcirculation. - M.: Medicine, 1984; Seleznev S.A. Clinical aspects of geometrically. - M.: Medicine, 1985; Kozinets GI Study of the blood system in clinical practice. - M.: Triada-X, 1997). Works devoted to the study of rheological properties of red blood cells in viral hepatitis a bit, and their results are ambiguous (Silenok IG - Sat. the scientific. Tr. "Clinical aspects of disorders of microcirculation and blood rheology" Bitter, 1984; Voitenko I.I. - La is oratorial case, 1988, No. 8; Saker Century - Dis... Kida. the honey. of Sciences, St. Petersburg, 1994; Maksimova EV - Dis... Kida. the honey. of Sciences, St. Petersburg, 1996). As the closest analogue was used Organically "Hemorheological disorders in viral hepatitis in children and the rationale for their correction" (abstract... KMN, Ivanovo, 2000).

The technical result of the proposed method is forecasting a prolonged course of viral hepatitis a and b by evaluating the rheological parameters of erythrocytes in the dynamics of the acute period of the disease and detection of reduction of the deformability index (PD), index of aggregation (PA), high levels of microviscosity of erythrocyte membrane lipids (MWLE), reducing the number of discocytes, increase in microcirculation degenerative irreversibly transformed forms of erythrocytes (NOTES), as well as identifying extrahepatic vascular characters.

The essence of the proposed technical solution is that the dynamics of acute viral hepatitis in the peak and early convalescence (25-30 day sickness) determine the rheological parameters of erythrocytes and extrahepatic vascular signs.

The deformability of erythrocytes was estimated by the method of determining the initial velocity of filtration through a cellulose acetate filter with a pore diameter of 3 μm (Rai et al. - Laboratory work, 1991, No. 6). Aggregation determines the direct optical method of calculation of the index of aggregation (PA), the average unit size (CPA) and the percentage of non-aggregated RBCs (PNA). Cytoarchitectonic erythrocytes was investigated using fitokontrol microscopy. Cells identifitsirovali in accordance with the classification Geekazine (Problems of Hematology and blood transfusion, 1977, No. 7). The microviscosity of erythrocyte membrane lipids (MWLE) was studied using thin-layer chromatography, determining the ratio of cholesterol to phospholipids.

Was carried out the calculation of information content and predictive factors using serial analysis of Wald.

PC - prognostic factor was calculated by the formula:

PC=10×LgP1/P2, where

P1 is the frequency of occurrence of the trait in the group.

P2 is the frequency of occurrence of the feature in the comparison group.

The measure of informativeness (Ik) was determined using the criterion Kullback:

Ik=PC×0,5×(P1-P2)

Symptoms were considered informative for PC≥2,0 and when Ik≥0.5 in.

The analysis of Wald allowed us to identify the most informative clinical hemorheological indices for assessment of prognosis of viral hepatitis, which are presented in the table.

Prognostic criteria development protracted course of viral hepatitis (table), are the decrease in deformability in the dynamics of the disease -≤ 0,11 USD (PC+5,2; Ik=2,33), metric aggregation ≤ $ 1,11 (PC=+1,0; IC=0,18), high MVLA - ≥4,5 USD (PC=+2,3; Ik=0.5), and a significant decrease in the number of discocytes - ≤70% (PC=+4,1; Ik=0.9) and an increase in microcirculation degenerative pretheoretically (irreversibly transformed erythrocytes NOTES ≥13% (PC=+2,9; Ik=0,76), as well as the emergence and persistent preservation extrahepatic vascular signs (capillarity cheeks, Palmar erythema, telangiectasia) (PC=+8,8; Ik=by 5.87).

To illustrate the severity of clinical hemorheological disorders with prolonged viral hepatitis below is an extract from a case history of the child D., age 4, were treated with a diagnosis of acute viral hepatitis, severe form. The office received on the 10th day of the disease in the state of moderate severity: weakness, reduced appetite, nausea, abdominal pain, intense jaundice of the skin and sclera; liver protrudes from under the edge of the right costal arch 5 cm, painful on palpation; spleen - 1.5 cm, dark urine, ahalia feces. At admission revealed extrahepatic vascular signs (bright Palmar erythema, capillary cheeks, single telangiectasia). The early period of convalescence was fading Palmar erythema, spider veins, but steadfastly remained moderate capillary cheeks. The diagnosis is verified serolo is automatic, detection of markers of the acute phase HB-viral infection. In the biochemical analysis of blood showed hyperbilirubinemia due to the conjugated fraction with maximum intensity on the 7th day of jaundice (bilirubin total/conjugated - 254,9/172,3 µmol/l), hyperferritinemia (Alt - 7.4 mmol/tsp). Investigation of the rheological indicators revealed in the midst of illness phenomenon of the missing aggregation of red blood cells, reducing the number of discocytes (77%), increased echinocytes (- 21%) and stomatocytes (MUSIC - 4%), the decrease in deformability (0,11 USD), an increase of microviscosity of erythrocyte membrane lipids (6,05$). It was noted protracted course of hepatitis with the development of cholestasis. The child was discharged on the 75th day of the disease with residual effects in terms of increased liver, increasing the activity of Alat (2.4 mmol/tsp), remained HBsAg secretion that had the parallelism with persistent preservation missing aggregation (PA=1,0; PC=+1,0), reducing the number of discocytes (70%; PC=+4,1), deformability index (PD-0,11; PC=+5,2), increasing FROM 14%; PC=+2.5), and MWLE (4,5 USD; PC=+2,3); rate NOTES amounted to 7% (PC=-2,0) and the appearance of extrahepatic vascular signs (PC=+8,8). The sum of the prediction coefficients 21.9 (PC=1,0+4,1+5,2+2,5+2,3-2,0+8,8=21,9), that allowed us to predict a protracted course of viral hepatitis, because PC≥13, which was observed in the pain of the CSOs. 2 months after discharge from hospital (138 day of onset) against clinical and biochemical improvement (no complaints, termination selection HBsAg, increased prothrombin index up to 80%, reducing the Alat to 1.2 mmol/tsp) observed positive dynamics of indicators of cytoarchitectonic erythrocytes, MWLE. However, remained a persistent decrease in RBC aggregation, reflecting the incompleteness of the inflammatory process in the liver.

To illustrate the dynamics of hemorheological parameters during prolonged viral hepatitis And provide a statement of medical history of the patient I., aged 11, which has been treated with a diagnosis of acute viral hepatitis A (Anti-HAV IgM+), moderate severity. Doulton the period was characterized by diarrhoea and asteno vegetative options. Admitted to the hospital on the 9th day of illness in a state of moderate severity with marked jaundice of the skin, enlarged (up to 3 cm from the edge of the costal arch) and painful liver. Within 3 days of icteric period continued complaints of dyspeptic character. In the following days, intoxication syndrome was stopped, however, pointed to the increasing jaundice appeared itchy skin, ahalia Kala, was once nosebleeds. The total duration of icteric period was 17 days. In the biochemical analysis of blood with which tuplenie: bilirubin total/conjugated - 96,9/82,6 µmol/l; Alat - 8.0 mmol/tsp In the peak of the disease by increasing the main symptoms and development of cholestasis has been a considerable deterioration of the rheological parameters of red blood cells: increased MWLE (4,5 USD; PC=+2,3), the reduction of PD (0,09 USD; PC=+5,2), discocytes (60%; PC=+4,1), an increase in NOTES (19%; PC=+2,9), (20%; PC=+2,5), PA was 1.1 cu (PC=+1,0). The sum of the prediction coefficients has reached a threshold of + 13 (PC=2,3+5,2+4,1+2,9+2,5+1,0-5,0=13), that allowed us to predict a protracted course of hepatitis, which was observed in the patient.

The child was discharged on day 32 of the disease in satisfactory condition with residual effects in terms of increased liver (1 cm from the edge of the costal arch) and giperfermentemii (Alat 2.2 mmol/tsp). In follow-up moderate cytolysis syndrome persisted for 3 months after discharge from a hospital that had a parallelism-preserving violations in terms of cytoarchitectonic and aggregation of erythrocytes. To 6 months of recovery were observed recovery from hepatitis a and normalization of the rheological parameters of erythrocytes.

To illustrate hemorheological violations of acute viral hepatitis, here is the excerpt from the history balesi child So, 8 years with a diagnosis of acute viral hepatitis A (Anti-HAV IgM +), moderate severity. From the hearth of EVGA. It was noted acute onset of bolezn is. Doulton period of 7 days, proceeded on diarrhoeal type. Admitted to the hospital on the 8th day of the disease in the state of moderate severity due to severe jaundice of the skin, mild symptoms of intoxication, increased liver (3 cm from the edge of the costal arch). Extrahepatic vascular signs were absent (PC=-5,0). In the biochemical analysis of blood showed hyperbilirubinemia (total bilirubin/conjugated = 110,3/75,4 µmol/l), hyperferritinemia (Alat 7,0 mmol/tsp). In the midst of illness was observed a moderate decrease in erythrocyte deformability (to 0.127$; PC=is 3.5), the index of aggregation (1,14$; PC=-5,6), a decrease of discocytes (81%; PC=-2,6), increased reversibly transformed forms (7%; PC=-2,3) and irreversibly transformed forms (12%; PC=-2,0), as well as a slight increase of MWLE (3,54$; PC=-6,5). The sum of the prediction coefficients amounted to 27.5, which allowed to predict acute cyclic hepatitis, which was observed in the patient. In dynamics to the period of discharge from the hospital showed improvement of hemorheological parameters and clinical and biochemical recovery.

Thus, the proposed method allows to predict a protracted course of viral hepatitis a and b in children by identifying hemorheological disorders, contributing to the deterioration of the intrahepatic microcirculation and process plants the structure of the processes of structural and functional recovery of the liver.

Table

Hemorheological criteria predict a protracted course of viral hepatitis
IndicatorsThe range of fluctuationsPrognostic factor (PC)The measure of informativeness (Ik)
DD $ 0.12 and moreis 3.51,55
≤0,11+5,22,33
FROM %≤13-2,30,62
≥14+2,50,68
MUSIC,%≤12-2,00,51
≥13+2,90,76
Discocyte, %≥71-2,60,51
≤70+4,10,91
MWLE, $≥4,5+2,30,5
≤4,4-6,51,76
PA $ ≤1,11+1,00,18
≥1,12-5,61,05
Extrahepatic vascular signs+8,8the 5.7
No-5,0a 3.87
Note: if the algebraic summation of the PCs threshold is reached, +13 and above, then with probability 90-95% (p<0,05) we can predict the possibility of developing a protracted course of viral hepatitis. When the threshold of -13 it is possible to predict the development of acute viral hepatitis.

A method for predicting a protracted course of viral hepatitis in children by examining the dynamics of the acute period of performance deformability, aggregation of erythrocytes, microviscosity lipids in their membranes, changes of surface cytoarchitectonic of red blood cells by the number of discocytes and degenerative pretheoretically forms, characterized in that it further examine extrahepatic vascular signs, estimation of parameters is performed using prediction coefficients (PC), where PC=+5,2 when the value of the indicator strain (AP) ≤ $ 0,11, PC=is 3.5 when PD = 0,12 USD or more and the value of the index of aggregation (PA) ≤ 1,11 $ PC=+1.0, with PA ≥1,12 $ PC=-5,6; at high rates of microviscosity lipid membranes (MWLE) ≥4,5 $ PC=+2,3, MWLE ≤4,4 $ PC=-6,5; by reducing the number of discocytes up to 70% and less PC=+4,1, when the rate of discocytes ≥71% PC=-2,6; with increasing pretheoretically irreversibly-converted the data forms (MUSIC) ≥ 13% PC=+2,9, with MUSIC ≤12% PC=-2,0; with increasing reversible-transformed erythrocytes (FROM) ≥14% PC=+2,5, FROM≤13% PC=-2,3; when in acute viral hepatitis, extrahepatic vascular signs PC=+8,8, in their absence, PC=-5,0, summarize the prognostic factors and, if the sum of the prediction coefficients is +13 and above, predict a protracted course of viral hepatitis.



 

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