medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2026-097medsovet-10089Research ArticleГАСТРОЭНТЕРОЛОГИЯGASTROENTEROLOGYЭффективность и безопасность терапии фенофибратом при первичном билиарном холангите в реальной клинической практикеEffectiveness and safety of fenofibrate therapy in primary biliary cholangitis in real-life clinical practicehttps://orcid.org/0000-0002-5402-8266ПрашноваМ. К.PrashnovaM. K.

Прашнова Мария Константиновна, к.м.н., доцент Научно-клинического и образовательного центра гастроэнтерологии и гепатологии, Санкт-Петербургский государственный университет; главный врач, врач-гастроэнтеролог, ООО «Поликлиника Эксперт»

199034, Санкт-Петербург, Университетская набережная, д. 7–9,

197110, Санкт-Петербург, ул. Пионерская, д. 63а

Maria К. Prashnova, Cand. Sci. (Med.), Associate Professor of the Scientific, Clinical and Educational Center of Gastroenterology and Hepatology, St Petersburg State University; Chief Physician, Gastroenterologist, LLC “Polyclinic Expert”

7–9, Universitetskaya Emb., St Petersburg, 199034,

63, Pionerskaya St., St Petersburg, 197110

prashnova@mail.ruhttps://orcid.org/0000-0002-8821-6142РайхельсонК. Л.RaikhelsonK. L.

Райхельсон Карина Леонидовна, д.м.н., доцент, профессор Научно-клинического и образовательного центра гастроэнтерологии и гепатологии, Санкт-Петербургский государственный университет; профессор кафедры общей врачебной практики (семейной медицины), Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова

199034, Санкт-Петербург, Университетская набережная, д. 7–9,

197022, Санкт-Петербург, ул. Льва Толстого, д. 6–8

Karina L. Raikhelson, Dr. Sci. (Med.), Associate Professor, Professor of the Scientific, Clinical and Educational Center of Gastroenterology and Hepatology, St Petersburg State University; Professor of the Department of General Medical Practice (Family Medicine), Pavlov First Saint Petersburg State Medical University

7–9, Universitetskaya Emb., St Petersburg, 199034,

6–8, Lev Tolstoy St., St Petersburg, 197022

kraikhelson@mail.ruhttps://orcid.org/0000-0001-8159-9745ГомоноваВ. П.GomonovaV. P.

Гомонова Вероника Павловна, ассистент Научно-клинического и образовательного центра гастроэнтерологии и гепатологии, 

199034, Санкт-Петербург, Университетская набережная, д. 7–9

Veronika Р. Gomonova, Assistant at the Scientific, Clinical and Educational Center of Gastroenterology and Hepatology

7–9, Universitetskaya Emb., St Petersburg, 199034

veronikakovyazina@yandex.ruhttps://orcid.org/0000-0002-7590-8932ПазенкоЕ. В.PazenkoE. V.

Пазенко Екатерина Владимировна, к.м.н., младший научный сотрудник Научно-клинического и образовательного центра гастроэнтерологии и гепатологии, Санкт-Петербургский государственный университет; врач-гастроэнтеролог поликлиники с клинико-диагностическим центром, Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова

199034, Санкт-Петербург, Университетская набережная, д. 7–9,

197022, Санкт-Петербург, ул. Льва Толстого, д. 6–8

Ekaterina V. Pazenko, Cand. Sci. (Med.), Junior Researcher at the Scientific, Clinical and Educational Center of Gastroenterology and Hepatology, St Petersburg State University; Gastroenterologist of a Polyclinic with a Clinical Diagnostic Center, Pavlov First Saint Petersburg State Medical University

7–9, Universitetskaya Emb., St Petersburg, 199034,

6–8, Lev Tolstoy St., St Petersburg, 197022

kaboi@rambler.ruhttps://orcid.org/0000-0002-6738-6417МарченкоН. В.MarchenkoM. V.

Марченко Наталья Валерьевна, к.м.н., доцент Научно-клинического и образовательного центра гастроэнтерологии и гепатологии, СанктПетербургский государственный университет; врач-гастроэнтеролог, ООО «Поликлиника Эксперт»; врач-гастроэнтеролог амбулаторного центра трансплантологии, гепатологии и нефрологии, Российский научный центр радиологии и хирургических технологий имени академика А.М. Гранова

199034, Санкт-Петербург, Университетская набережная, д. 7–9,

197110, Санкт-Петербург, ул. Пионерская, д. 63а,

197758, Санкт-Петербург, поселок Песочный, ул. Ленинградская, д. 70

Nataliya V. Marchenko, Cand. Sci. (Med.), Associate Professor of the Scientific, Clinical and Educational Center of Gastroenterology and Hepatology, St Petersburg State University; Gastroenterologist, LLC “Polyclinic Expert”; Gastroenterologist at the Outpatient Center for Transplantation, Hepatology and Nephrology, Russian Scientific Center for Radiology and Surgical Technologies named after Academician A.M. Granov

7–9, Universitetskaya Emb., St Petersburg, 199034,

63, Pionerskaya St., St Petersburg, 197110,

70, Leningradskaya St., Peschany Settlement, St Petersburg, 197758

dr.marchenko@gmail.comhttps://orcid.org/0009-0000-8806-2393СоколоваК. С.SokolovaK. S.

Соколова Ксения Сергеевна, ассистент Научно-клинического и образовательного центра гастроэнтерологии и гепатологии, Санкт-Петербургский государственный университет; врач-гастроэнтеролог, ООО «Поликлиника Эксперт»; врач-гастроэнтеролог хирургического отделения №6 (трапсплантации органов и гепатопанкреатобилиарной хирургии), Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова

199034, Санкт-Петербург, Университетская набережная, д. 7–9,

197110, Санкт-Петербург, ул. Пионерская, д. 63а,

197022, Санкт-Петербург, ул. Льва Толстого, д. 6–8

Ksenia S. Sokolova, Assistant at the Scientific, Clinical and Educational Center of Gastroenterology and Hepatology, St Petersburg State University; Gastroenterologist, LLC “Polyclinic Expert”; Gastroenterologist of Surgical Department No. 6 (Organ Transplantation and Hepatopancreatobiliary Surgery), Pavlov First Saint Petersburg State Medical University

7–9, Universitetskaya Emb., St Petersburg, 199034,

63, Pionerskaya St., St Petersburg, 197110,

6–8, Lev Tolstoy St., St Petersburg, 197022

sokolova.mdd@gmail.comСанкт-Петербургский государственный университет; ООО «Поликлиника Эксперт»РоссияSt Petersburg State University; LLC “Polyclinic Expert”Russian FederationСанкт-Петербургский государственный университет; Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. ПавловаРоссияSt Petersburg State University; Pavlov First Saint Petersburg State Medical UniversityRussian FederationСанкт-Петербургский государственный университетРоссияSt Petersburg State UniversityRussian FederationСанкт-Петербургский государственный университет; ООО «Поликлиника Эксперт»; Российский научный центр радиологии и хирургических технологий имени академика А.М. ГрановаРоссияSt Petersburg State University; LLC “Polyclinic Expert”; Russian Scientific Center for Radiology and Surgical Technologies named after Academician A.M. GranovRussian FederationСанкт-Петербургский государственный университет; ООО «Поликлиника Эксперт»; Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. ПавловаРоссияSt Petersburg State University; LLC “Polyclinic Expert”; Pavlov First Saint Petersburg State Medical UniversityRussian Federation20263105202620594--101Copyright © Прашнова М.К., Райхельсон К.Л., Гомонова В.П., Пазенко Е.В., Марченко Н.В., Соколова К.С., 20262026Прашнова М.К., Райхельсон К.Л., Гомонова В.П., Пазенко Е.В., Марченко Н.В., Соколова К.С.Prashnova M.K., Raikhelson K.L., Gomonova V.P., Pazenko E.V., Marchenko M.V., Sokolova K.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/10089Введение

Введение. Данные рандомизированных клинических исследований и метаанализов демонстрируют эффективность терапии фибратами у резистентных к урсодезоксихолевой кислоте (УДХК) пациентов с первичным билиарным холангитом (ПБХ), однако все еще мало информации об использовании фенофибрата в реальной клинической практике при ПБХ.

Цель

Цель. Оценить эффективность и безопасность терапии фенофибратом у амбулаторных пациентов с ПБХ, имеющих недостаточный биохимический ответ и/или непереносимость УДХК.

Материалы и методы

Материалы и методы. Произведена ретроспективная оценка частоты ответа на лечение, нежелательных явлений (НЯ) и ухудшения течения болезни печени у 63 пациентов с ПБХ, рефрактерных к монотерапии УДХК, получающих терапию фенофибратом 145–200 мг/сут в сочетании с УДХК 13–15 мг/кг/сут не менее 6 мес. (в среднем 21,0 ± 12,8 мес.). Средняя продолжительность болезни до постановки диагноза – 35,4 ± 38,4 мес., доля пациентов с поздней стадией ПБХ до начала терапии – 68,3%.

Результаты

Результаты. Ответы по Paris-II, GLOBE и полный биохимический ответ достигнуты в 54,0%, 58,7% и 25,4% соответственно и были отрицательно ассоциированы с наличием клинически значимой портальной гипертензии (p = 0,0006, p = 0,006, p = 0,001 соответственно). Добавление фенофибрата к УДХК снизило частоту кожного зуда с 60,6 до 18,2%, р = 0,0005. Зарегистрированы следующие НЯ: миалгии (n = 10); бессимптомный холецистолитиаз (n = 6); повышение АЛТ в 5 и более раз от исходных уровней, регрессировавшее при отмене препарата (n = 2), у 1 пациента серьезное НЯ – кровотечение из варикозно расширенных вен пищевода (ВРВП), вероятно, не связанное с приемом препарата. Отмечено увеличение частоты анемии в 1,7 раза, ассоциированное с коморбидными состояниями. Терапия фенофибратом не сопровождалась статистически значимым нарастанием частоты выявления поздней стадии ПБХ, клинически значимой портальной гипертензии, а также показателя MELD y пациентов с циррозом.

Выводы

Выводы. Добавление фенофибрата к УДХК при ПБХ, рефрактерном к УДХК, увеличивает частоту достижения ответа на лечение и представляется достаточно безопасным.

Introduction

Introduction. Randomized clinical trials and meta-analyses demonstrate the efficacy of fibrate therapy in ursodeoxycholic acid (UDCA)-resistant patients with primary biliary cirrhosis (PBC). However, there is still limited information on the efficacy and safety of fenofibrate use in routine clinical practice in PBC.

Aim

Aim. To evaluate the efficacy and safety of fenofibrate therapy in outpatients with PBC, who have an insufficient response and/ or are intolerant to UDCA.

Materials and methods

Materials and methods. A retrospective assessment of treatment response (complete biochemical response, Paris-II, GLOBE scores), adverse events, and disease progression was performed in 63 patients with PBC refractory to UDCA monotherapy, receiving fenofibrate at 145–200 mg daily in combination with UDCA at 13–15 mg/kg/day for at least 6 months (average 21.0 ± 12.8 months). The mean disease duration before diagnosis was 35.4 ± 38.4 months, and the proportion of patients with advanced-stage PBC before therapy was 68.3%.

Results

Results. Paris-II, GLOBE and complete biochemical response rates were 54.0%, 58.7% and 25.4%, respectively, and were negatively associated with the presence of clinically significant portal hypertension (CSPH) (p = 0.0006, p = 0.006, p = 0.001, respectively). The addition of fenofibrate to UDCA reduced the incidence of skin itching from 60.6% to 18.2% (p = 0.0005). The following adverse events (AE) were reported during fenofibrate therapy: myalgia (n = 10); asymptomatic cholecystolithiasis (n = 6); an increase in ALT by 5 or more times from baseline levels, which regressed upon drug discontinuation (n = 2); one patient had a serious AE – bleeding from esophageal varices, probably not related to the medication. A 1.7-fold increase in the incidence of anemia associated with comorbid conditions was noted. Fenofibrate therapy was not associated with a statistically significant increase in the incidence of advanced-stage PBC, clinically significant portal hypertension, or the MELD score in patients with cirrhosis.

Conclusions

Conclusions. The addition of fenofibrate to UDCA in UDCA-refractory PBC increases the response rate and appears to be quite safe.

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