Abstract
Rationale: Search for predictors of aggressive course of chronic hepatitis C virus (HCV) infection in individual patients, including genetic studies, is considered to be a major urgent goal. High rates of fibrosis progression in chronic HCV infection is associated with several gene polymorphisms coding for the components of renin-angiotensin system and involved in the formation of endothelial dysfunction and oxidative stress. Aim: To develop a predictive model to assess the probability of rapid fibrosis progression in patients with chronic HCV infection based on the combination of the known genetic markers, clinical and demographic parameters. Materials and methods : One hundred and nine patients with chronic HCV infection (79 women and 30 men) of known duration and liver fibrosis were categorized into the groups with “rapid fibrosis” (n = 54, the rate of fibrosis progression ≥ 0.13 fibrosis units / year) and with “slow fibrosis” (n = 55, the rate of progression < 0.13 fibrosis units / year). Polymorphisms of the studied genes were assessed by molecular genetic assays. Multivariate analysis of the influence of combination of genetic variants, as well as of the interaction of genetic, clinical and demographic factors on the rate of fibrosis progression in the patients with chronic HCV infection was performed by logistic regression method. Results: The rapid rate of fibrosis progression was significantly associated with patient's age at the time of infection (Wald statistics 14.955; p = 0.00011), male gender (Wald statistics 6.787; p = 0.00918), (-6)АА genotype of the AGT gene carriage (Wald statistics 6.512; p = 0.01072), 242ТТ-genotype of the CYBA gene (Wald statistics 4.347; p = 0.03708), and 235МТ genotype of the AGT gene (Wald statistics 4.306; p = 0.03799). The model to predict the probability of rapid fibrosis progression in individuals with chronic HCV infection included the above mentioned factors; its use was demonstrated with two clinical cases. Conclusion : The analysis of the AGT gene (M235T and G-6A loci) and the СYBA gene (C242T locus) polymorphisms are relevant to identify patients at risk of rapid liver fibrosis progression. In this case, 242ТТ genotype of the CYBA gene and (-6)AA and 235MT genotypes of the AGT gene are considered unfavorable. To refine the prognosis, it is necessary to take into account demographic parameters (gender and age at the moment of infection contraction), because male gender and older age of getting the infection would increase the probability of rapidly progressive of hepatitis C.
Highlights
A 7-gene signature of the recipient predicts the progression of fibrosis after liver transplantation for hepatitis C virus infection
Combined effect of an ACE inhibitor, perindopril, and interferon on liver fibrosis markers in patients with chronic hepatitis C
Summary
Диагнозы ХГС и цирроза печени вирусной (С) этиологии были установлены на основании жалоб, анамнеза, объективного обследования и данных стандартных лабораторных и инструментальных методов, включая ультразвуковое исследование (УЗИ) органов брюшной полости, доплерографию сосудов печени и нижней полой вены, эзофагогастродуоденоскопию (по показаниям). Определение стадии фиброза печени проводилось по шкале METAVIR методом чрескожной биопсии печени с последующим гистологическим исследованием (у 89 больных), эластометрии печени (у 8 пациентов) на аппарате FibroScan (Echosens, Франция), в 2 случаях данные эластометрии были подтверждены результатами анализа комплекса серологических маркеров фиброза (Фиброактитест, BioPredictive, Франция). У 12 больных стадия фиброза была расценена как F4 по данным клинико-лабораторных и инструментальных методов без проведения эластометрии и биопсии печени. Для оценки темпа прогрессирования фиброза по единственной биопсии печени [3]: Скорость прогрессирования фиброза [ед. Где F – стадия фиброза печени по шкале METAVIR Длительность заболевания рассчитывалась как период от желтушной формы острого вирусного гепатита С или от наиболее раннего из равнозначных факторов риска (первая внутривенная инъекция наркотика, первая трансфузия цельной крови или ее компонентов, полостная операция) до определения стадии фиброза печени. Анализ полиморфизма исследуемых генов проводился молекулярно-генетическими методами, описанными ранее [16, 17, 27]
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