Abstract
Objective: to estimate the time course of changes in the levels of tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, and the hepatic fibrosis indicators hyaluronic acid (HA) and liver elasticity index during combined antiviral therapy (AVT) with interferon alpha-2b and ribavirin in patients with chronic hepatitis C (CHC). Subjects and methods. Fifty patients with CHC were examined. Serum TNF-α, IL-6, IL-4, and HA were estimated using an enzyme immunoassay. The stage of hepatic fibrosis was determined by fibroelastography with the liver elastic index being measured; the time course of changes in the indicators was assessed in 20 patients at the end of AVT. A virological response was monitored at therapy completion and 6 months later. Results. The patients with CHC in the reactivation phase were found to have enhanced TNF-α, IL-6, and IL-4 activities in 84, 60, and 100 % of the cases, respectively (р < 0.001, р = 0.01, р < 0.001, respectively). The median serum concentration of HA in CHC was 1.8-fold higher than that in the control group (p = 0.03); the liver elastic index averaged 6.5 kPa. TNF-α and IL-6 levels correlated with viremia, transaminases, and hepatic fibrosis indicators. At combined AVT completion, the virological response rate was as high as 85 %, which was attended by a considerable reduction in cytolysis, HA concentrations, and liver density index to 5.4 kPa (3.6–6.8 kPa) (p < 0.04), and in the activity of the examined cytokines. The sustained virological response rate was 80 %. Only IL-4 levels decreased and TNF-α and IL-6 concentration remained at the baseline level in patients unresponsive to AVT. Conclusion. It is expedient to monitor TNF-α, IL-4, IL-6, and HA to evaluate the severity of liver involvement in CHC and to predict the efficiency of AVT.
Highlights
Ключевые слова: хронический гепатит С, цитокин, фактор некроза опухоли-α, интерлейкин-4, интерлейкин-6, гиалуроновая кислота, фиброз печени, эластография, индекс эластичности печени, виремия, противовирусная терапия, рибавирин, интерферон альфа-2b
The stage of hepatic fibrosis was determined by fibroelastography with the liver elastic index being measured; the time course of changes in the indicators was assessed in 20 patients at the end of antiviral therapy (AVT)
tumor necrosis factor-α (TNF-α) and IL-6 levels correlated with viremia, transaminases, and hepatic fibrosis indicators
Summary
Цель исследования – оценить динамику концентраций ФНО-α, ИЛ-4, ИЛ-6 и показателей фиброза печени – гиалуроновой кислоты (ГК) и индекса эластичности печени – под влиянием комбинированной ПВТ интерфероном альфа-2b и рибавирином у больных ХГС. Результаты и обсуждение При исследовании биохимических показателей у пациентов с ХГС в фазе реактивации были обнаружены нарушения функциональных печеночных проб в виде синдрома цитолиза, который характеризовался увеличением в сыворотке крови активности АЛТ (р < 0,001) и АСТ (р < 0,001) В группе больных ХГС повышение содержания ГК в сыворотке крови выявлено у 43 % (n = 21), что отражает активацию фиброза на фоне хронического воспаления печени, при этом медиана концентрации ГК в сыворотке крови в 1,8 раза превышает этот показатель в группе контроля (р = 0,03). Показателей фиброза печени и цитокинов у больных ХГС на фоне ПВТ, Ме (25–75-й перцентили)
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