Аналіз показників фіброгенезу у хворих на хронічний гепатит С

Abstract

Робота присвячена вивченню сироваткових маркерів фіброзу печінки - трансформуючого фактора росту - βi (TGF-β1) і тканинного інгібітора металопротеінази-1 (ТІМП-1), та фіброеластометрії для встановлення ступеня фіброзу у хворих на хронічний гепатит С. Аналізуючи рівні цитокінів фіброгенезу та показники фіброеластометрії у 177 хворих на ХГС встановлено статистично достовірний зв’язок (р<0,01) між цими показниками при фіброзі печінки F2 івище. Виявлено, що сироваткові рівні TGF-β1 та TIMPs-1 є достовірно вищими у хворих на ХГС з високим вірусним навантаженням, ніж з низьким. Отже, показники TGF- β1 і TIMPs-1 можуть бути використані для диференційної діагностики високих ступенів фіброзу печінки у якості додаткового тесту для підтвердження діагнозу; Работа посвящена изучению сывороточных маркеров фиброза печени - трансформирующего фактора роста - β1 (TGF-β1) и тканевого ингибитора металопротеиназы -1 (ТІМП-1), а также фиброэластометрии для установления степени фиброза у больных хроническим гепатитом С. Анализируя уровни цитокинов фиброгенеза TGF-β1 и ТІМП-1, и показатели фиброэластометрии у 177 больных ХГС, установлено статистически достоверную связь (р<0,01) между этими показателями при фиброзе печени F2 и выше. Выявлено, что сывороточные уровни TGF-βi и TIMPs-1 достоверно выше у больных ХГС с высокой вирусной нагрузкой, чем с низкой. Итак, показатели TGF- βi и TIMPs-1 могут быть использованы для дифференциальной диагностики высоких степеней фиброза печени в качестве дополнительного теста для подтверждения диагноза; The clinical course of chronic hepatitis C (CHC) largely depends on the progression rate and fibrosis degree. The serum markers - tissue inhibitor metalloproteinase-1 (TIMPs-1) and transforming growth factor - β1 (TGF-β1), which are considered the key markers among cytokines of liver fibrogenesis, are relevant in this aspect. The aim of research was to study the levels of cytokines of liver fibrogenesis TIMPs-1and TGF-β1 in patients with CHC depending on the degree of fibrosis and viral load. Object and methods of research. The study included 177 patients with CHC aged from 31 to 70 years (54.1±1.1): 95 (53.7 %) men and 82 (46.3 %) women who were treated in the gastroenterological department of Transcarpathian Regional Clinical Hospital named after A. Novak, Uzhgorod. Depending on the complaints, all patients underwent clinical and laboratory examinations according to protocols of medical care of probable disease. The degree of liver fibrosis was determined using a non-invasive method of diagnostics - FibroMax (BioPredictive, Paris) and indirect transient elastometry of the liver (“FibroScan” 502 F01261, France). Evaluation of TIMPs-1and TGF-β1 in the blood serum was carried out by ELISA method (test-systems DRG, USA). The initial viral load was evaluated in all CHC patients. Patients were distributed into 1a subgroup (n=71) with the high viral load (HVL) HCV RNA > 6x105 lU/ml, respectively. Results and discussion. According to indirect transient elastometry in 14 (7,9%) CHC patients fibrosis was not revealed, in 22 (12.40%) the first stage was identified, in 38 (21.5%) - the second stage, in 82 (46.3 %) - the third stage and in 21 (11.9%) - the fourth stage of fibrosis according to METAVIR scale. While examining the levels of TGF-β1 and TIMPs-1 in patients with CHC it was determined that the level of TGF- β1 was elevated in 141 (79.7 %) of patients, reduced in 15 (8.5 %) and that corresponded to the normal values in 21 (11.9 %) of patients. The level TIMPs-1 was elevated in 130 (73.4 %) of patients, decreased in 12 (6.8 %) and that corresponded to indicators of control group in 35 (19.8 %). When studying the possible correlations between the levels of fibrogenesis cytokines and viral load it was determined that the level TGF- β1 and TIMPs-1 in CHC patients with high viral load was significantly higher (p<0.05) in comparison with the corresponding indicator at low viral load. Comparing the levels of cytokines and degrees of liver fibrosis according to indirect transient elastometry data it was stated the statistically significant correlation (p<0.01) between TGF-β1 and TIMPs-1 levels and the degree of liver fibrosis (r=0.78 and r=0.71) in CHC patients when liver fibrosis was F2 and higher. When examining relations between cytokines levels and concentration of cytolytic enzymes, the correlation between TGF-βi and TIMPs-1 concentration, on the one hand, and AST/ALT ratio, on the other (r=0.61, r=0.58, p<0.01 and r=0.68, r=0.62, p<0.01, correspondingly) was determined. Conclusions 1. In CHC patients the serum levels TGF-β1 and TIMPs-1 are significantly higher in case of the higher viral load than in low one. 2. Statistically significant correlation (p<0.01) between the serum levels TGF-β1 and TIMPs-1 and liver fibrosis F2 and higher was determined.