oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2019-18-3-90-96oncotomsk-1101Research ArticleОБЗОРЫREVIEWSЭРАДИКАЦИЯ HCV-ИНФЕКЦИИ НА СТАДИИ ЦИРРОЗА ПЕЧЕНИ: ФАКТОР КАНЦЕРОПРЕВЕНЦИИ ИЛИ КАНЦЕРОГЕНЕЗА?ERADICATION OF HCV INFECTION IN PATIENTS WITH LIVER CIRRHOSIS: FACTOR OF CANCER PREVENTION OR CARCINOGENESIS?https://orcid.org/0000-0002-0829-474XМалининаН. А.MalininaN. A.

Малинина Наталья Анатольевна, аспирант кафедры госпитальной терапии РУДН, врач Центра изучения печени

г. Москва, 117198, ул. Миклухо-Маклая, 10

Researcher ID (WOS): I-9426-2018

Nataliya A. Malinina, MD, Postgraduate, Liver Research Center, Department of Hospital Therapy

10, Street Miklouho-Maclay, 117198-Moscow

Researcher ID (WOS): I-9426-2018

malininan20042013@yandex.ruМазурчикН. В.MazurchikN. V.

Мазурчик Наталья Владимировна, кандидат медицинских наук, доцент кафедры госпитальной терапии РУДН, заместитель директора Центра изучения печени РУДН

г. Москва, 117198, ул. Миклухо-Маклая, 10

Nataliya V. Mazurchik, MD, PhD, Liver Research Center, Department of Hospital Therapy

10, Street Miklouho-Maclay, 117198-Moscow

mazurchikn@yandex.ruТарасоваО. И.TarasovaO. I.

Тарасова Ольга Ивановна, кандидат медицинских наук, доцент кафедры госпитальной терапии РУДН, врач Центра изучения печени РУДН

г. Москва, 117198, ул. Миклухо-Маклая, 10

Olga I. Tarasova, MD, PhD, Associate Professor at the Department of Hospital Therapy, doctor of the Center for the Study of the Liver

10, Street Miklouho-Maclay, 117198-Moscow

hildegarda@mail.ruhttps://orcid.org/0000-0001-7939-891XОгурцовП. П.OgurtsovP. P.

Огурцов Павел Петрович, доктор медицинских наук, профессор, заведующий кафедрой госпитальной терапии РУДН, директор Центра изучения печени РУДН

г. Москва, 117198, ул. Миклухо-Маклая, 10

Researcher ID (WOS): А-5844-2017.

Author ID (Scopus): 6602445752

Pavel P. Ogurtsov, MD, Professor, Liver Research Center, Head of Department of Hospital Therapy

10, Street Miklouho-Maclay, 117198-Moscow

Researcher ID (WOS): А-5844-2017.

Author ID (Scopus): 6602445752

pogurtsov@yandex.ruРоссийский университет дружбы народовРоссияPeoples' Friendship University of RussiaRussian Federation2019300620191839096Copyright © Малинина Н.А., Мазурчик Н.В., Тарасова О.И., Огурцов П.П., 20192019Малинина Н.А., Мазурчик Н.В., Тарасова О.И., Огурцов П.П.Malinina N.A., Mazurchik N.V., Tarasova O.I., Ogurtsov P.P.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/1101

Гепатоцеллюлярная карцинома – одна из наиболее распространенных причин онкологической смертности и финальная стадия хронических заболеваний печени, как правило, формирующаяся у больных циррозом печени. Вирус гепатита С (HCV) обладает тропностью к печеночной ткани, а хроническое инфицирование этим вирусом приводит к прогрессирующему воспалению печени и развитию цирроза. Ранее применяемая терапия интерферонами (ИФН) имела относительно низкую эффективность и высокие риски развития побочных эффектов. В период применения ИФН было доказано, что элиминация вируса существенно снижает риск развития рака печени. Появление препаратов прямого противовирусного действия (ПППД) произвело революцию в лечении вирусного гепатита С с частотой элиминации вируса более 98 % и отличным профилем безопасности. Однако риск трансформации цирроза печени в гепатоцеллюлярную карциному остается высоким даже после эрадикации вируса ПППД. Опубликованные в настоящее время многочисленные исследования с противоречивыми результатами по вопросам возможной связи применения противовирусных препаратов прямого действия и увеличением частоты выявления или рецидива гепатоцеллюлярной карциномы предопределили проведение данного исследования.

Цель исследования – анализ отечественной и зарубежной литературы о влиянии противовирусной терапии хронического гепатита С интерферон-содержащими схемами и препаратами прямого противовирусного действия на риск развития или рецидива гепатоцеллюлярной карциномы.

Материал и методы

Материал и методы. Проведен поиск доступных русскои англоязычных статей, опубликованных в базах данных PubMed, Scopus, E-library, Web of S cience, по ключевым словам: гепатоцеллюлярная карцинома, хронический гепатит С, препараты прямого противовирусного действия, цирроз печени, интерфероны, устойчивый вирусологический ответ, hepatocellular carcinoma, chronic hepatitis C, direct antiviral drugs, liver cirrhosis, interferons, sustained virologic response. Из 99 найденных исследований 21 было использовано для написания систематического обзора.

Результаты

Результаты. Эрадикация вируса снижает риски ГЦК. Несмотря на сообщения о более высоком риске возникновения или рецидива гепатоцеллюлярной карциномы у пациентов с циррозом печени в исходе хронического гепатита С после лечения ПППД по сравнению с интерферон-содержащими схемами, пока недостаточно данных, подтверждающих прямую связь между использованием ПППД и развитием гепатоцеллюлярной карциномы. При коррекции данных с учетом факторов риска статистически значимой разницы в частоте диагностики ГЦК между пациентами, получавшими лечение интерфероном или ПППД, не обнаружено.

Заключение

Заключение. Эрадикация вируса является наиболее значимым фактором профилактики ГЦК, поэтому лечение ХГС не должно откладываться из-за риска развития ГЦК. Пациенты с циррозом печени требуют длительного периода наблюдения, даже после успешной терапии ХГС препаратами прямого противовирусного действия. Стратификация рисков ГЦК требует дальнейших исследований.

Hepatocellular carcinoma (HCC) is one of the most common causes of death from cancer and is the final stage of chronic liver disease, usually occurring in patients with cirrhosis (CP). Chronic infection with hepatitis C virus (HCV) leads to progressive liver inflammation and cirrhosis because this virus specifically affects liver tissue. Previously used interferon therapy had a relatively low efficiency and very high risks of side effects. During the period of administration of interferon (IFN) schemes it was proved that elimination of the virus significantly reduced risk of liver cancer development. Discovery of direct-acting antiviral (DAA ) drugs have revolutionized HCV therapy with virus elimination rate of more than 95 % and an excellent safety profile. However, the risk of transformation of liver cirrhosis into hepatocellular carcinoma is still high even after complete eradication of the virus. Numerous studies have shown conflicting results on the possible relationship between the use of new antiviral drugs and the increase in the frequency of newly diagnosed or recurrent hepatocellular carcinoma. Thus, the long-term prognosis in terms of risk for HCC development among patients with sustained virological response (SVR) remains unclear.

The purpose of the study was to analyze the literature on the effect of antiviral therapy of chronic hepatitis C with interferon-containing regimens and drugs of direct antiviral action on the risk of developing or recurring hepatocellular carcinoma.

Material and Methods

Material and Methods. We analyzed publications available from PubMed, S copus, E-library, Web of S cience using the key words “hepatocellular carcinoma”, “chronic hepatitis C”, “direct-acting antiviral drugs”, “liver cirrhosis”, “interferons”, and “sustained virological response”. Of the 99 studies found, 21 were used to write a systematic review.

Results

Results. Eradication of the virus reduces the risks of HCC. Despite reports on high risk of occurrence or recurrence of hepatocellular carcinoma in patients with cirrhosis after treatment with DAA s compared with interferon-containing regimens, there is not enough data confirming the direct link between the use of DAA s and the development of hepatocellular carcinoma. No statistically significant difference in the frequency of HCC between patients treated with interferon or DAA s was detected.

Conclusion

Conclusion. Eradication of the virus is the most significant factor in the prevention of HCC; therefore, treatment of CHC should not be delayed due to the risk of HCC. Patients with liver cirrhosis require a long period of follow-up, even after successful treatment of chronic hepatitis C with DAA drugs. Stratification of HCC risk requires further research.

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The authors declare that there are no conflicts of interest present.