Predicting the rate of liver fibrosis in patients with chronic hepatitis C virus infection based on the combination of genetic and environmental factors

Autor: O. V. Taratina, L. M. Samokhodskaia, T. N. Krasnova, N. A. Mukhin
Jazyk: ruština
Rok vydání: 2017
Předmět:
Zdroj: Alʹmanah Kliničeskoj Mediciny, Vol 45, Iss 5, Pp 392-407 (2017)
Druh dokumentu: article
ISSN: 2072-0505
2587-9294
DOI: 10.18786/2072-0505-2017-45-5-392-407
Popis: 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.
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