Роль эндогенных антимикробных пептидов при оценке тяжести течения гепатита С в сочетании с пневмонией

Abstract

Метою даного дослідження було вивчення маркерів ендотоксемії (дефензіни, ендотоксину і ліпополісахарид-зв’язуючого білка) і виявлення їх ролі в патогенезі хронічного вірусного гепатиту С. Представляється можливим використання дефензінів, ендотоксину, ліпополісахарид-зв’язуючого білка як додаткових біомаркерів вірусних і бактеріальних інфекцій, а ендотоксину – як кількісного маркера динаміки і ступеня тяжкості ушкодження печінки при хронічному гепатиті С; Целью данного исследования явилось изучение маркеров эндотоксемии (дефензинов, эндотоксина и липополисахарид-связывающего белка) и выявление их роли в патогенезе хронического вирусного гепатита С. Представляется возможным использование дефензинов, эндотоксина, липополисахарид-связывающего белка как дополнительных биомаркеров вирусных и бактериальных инфекций, а эндотоксина – в качестве количественного маркера динамики и степени тяжести повреждения печени при хроническом гепатите С; The aim of this research was to study the markers of endotoxemia (defensins, endotoxins and lipopolysaccharide binding protein) and determine the relationship with immune indicators in pathogenesis of chronic viral hepatitis C. Blood samples of 90 patients at the age of 17-38 was examined, wit patients divided into 3 groups: I group – 25 patients with chronic hepatitis C, II group – 25 patients with pneumonia, III group – 40 patients with chronic hepatitis C combined with pneumonia. The control group consisted of 13 healthy donors. The diagnosis of chronic viral hepatitis was made according to the classification of the World Congress of Gastroenterology (Los Angeles, 1994). Biochemical evaluation was carried out by examining such markers as total, direct and indirect bilirubin with Endrashika method; ALT, AST – with Reitman-Frankel’s method, activity of enzyme of gamma-glutam yltransferase – using commercial kits produced by «Diasys» firm (Germany). Determination of the concentration of endotoxin and lipopolysaccharide-binding protein (LBP) was conducted by enzyme-linked immunosorbent assay (ELISA) with the «sandwich» principle with the help of ELISA kit from «HyCult Biotechnology» company (Netherlands). Statistical data processing was carried out with the help of Wilcoxon U-test (Mann-Whitney). All biochemical parameters (namely, bilirubin and its fractions, ALT) were significantly higher in all patients compared to the norm, and in I and III groups expression of these changes corresponded to the activity and clinical manifestations of hepatitis C. In II group, these changes were minor. A typical criterion of deterioration and poor prognosis was an increase in the levels of AST and ALT, as well as in levels of enzyme of gamma-glutamyltransferase, indicating heavy necrobiosis of hepatocytes. Bacterial infection is one of the most frequent complications in patients with liver problems. Probably, the most significant changes in III group of patients are associated with this. The amount of endotoxin in HCV in I group was 25,0 ± 4.9 EU/ml, while in II group this figure stood at 38,5 ± 6,7 EU/ml, and III group – 57,3 ± 9,3 EU/ml with the control value at 0,01 ± 0,07 EU/ml. It is known that in chronic viral hepatitis the concentration of endotoxin in bloodstream may repeatedly increase primarily due to violation of the detoxifying function of the liver, an increase in the permeability of the intestinal tube, the development of the syndrome of bacterial overgrowth, thus promoting the development of endotoxin aggression. Endotoxin can cause or accelerate immune inflammation through multiple mechanisms and stimulates the production of defensins, which are quite informative markers of the severity of the inflammatory process. Thus, defensin levels in I group increased by 8,1 times (313,4 ± 50,1 ng/ml) with the control at 38,6 ± 6,9 ng/ml, while in II group it increased by 2,6 times (840,5 ± 69.8 ng/ml) and in III group – by 4 times (1282,5 ± 125,2 ng/ml) compared to I group of patients. It should be noted that LBP levels correlate with severity of infection in liver. The highest level was observed in III group – a 17,2 times increase (407,0 ± 28,8 ng/ml), while in group I there was a 5.2 times increase (124,0 ± 7,9 ng/ml) and in II group – 12,3 times increase (291,4 ± 20,1 ng/ml) compared to the control value. On the one hand, increasing LVP values may reflect the severity of endotoxemia syndrome, while on the other hand – the activation of antiendotoxic immunity. The level of lipopolysaccharide binding protein increases rapidly in the presence of a bacterial infection that does not exclude its use for quantification of endotoxemia and as a marker of emerging inflammation. Overall, it is possible to use defensins, endotoxins and lipopolysaccharide binding protein as additional biomarkers of viral and bacterial infections, while endotoxin – as a quantitative marker of dynamics and severity of liver damage at chronic hepatitis C.