ОЦЕНКА ВЛИЯНИЯ ПОЛИМОРФИЗМОВ ГЕНОМА ВИРУСА ГЕПАТИТА С НА ФОРМИРОВАНИЕ ГЕПАТОЦЕЛЛЮЛЯРНОЙ КАРЦИНОМЫ (ОБЗОР ЛИТЕРАТУРЫ)

Цель обзора: провести оценку влияния вируса гепатита С (ВГС) и полиморфизмов его генома на формирование гепатоцеллюлярной карциномы (ГЦК).

Основные положения: Развитие ГЦК остается нерешенным и сложным вопросом современной системы здравоохранения. Одним из наиболее значимых факторов риска формирования ГЦК является инфицирование гепатотропными вирусами, в частности ВГС. Установлено, что все белки ВГС (Core, E1, E2, p7, NS2, NS3, NS4A, NS4B, NS5A, NS5B) так или иначе приводят к нарушениям клеточного деления и работы иммунной системы, включая снижение эффективности NK- и T-клеток. Ингибирование активности проапоптотического белка p53, снижение выработки интерферонов и их противовирусной активности, а также дисрегуляция работы белков супрессоров опухолевого роста провоцируют развитие опухолевого процесса в тканях печени. Высокая изменчивость ВГС обусловлена частым возникновением мутаций в его геноме, часть из которых может приводить к возникновению аминокислотных замен в вирусных протеинах и еще больше усиливать проонкогенные процессы в организме больного. Такие мутации изучены для генов E2, NS5A, но в большей степени – для core гена вируса. Заключение: Наиболее часто встречающимися аминокислотными заменами в core-белке ВГС,закрепившимися в популяции вируса и выявляемыми в когорте пациентов с ГЦК, являются R70Q/H, L91M и K10Q/R. Проведенный анализ существующей научной литературы по данной теме подтвердил актуальность изучения и оценки распространенности полиморфизмов ВГС, провоцирующих развитие ГЦК среди пациентов с хроническим вирусным гепатитом С, что может стать базой для создания тест-системы, основанной на методике ПЦР с целью выявления пациентов, инфицированных вариантами ВГС с наличием проонкогенных генетических детерминант в геноме для прогнозирования развития злокачественного процесса.

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