medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2026-204medsovet-10126Research ArticleЗАБОЛЕВАНИЯ БИЛИАРНОЙ СИСТЕМЫ И ПЕЧЕНИDISEASES OF THE BILIARY SYSTEM AND LIVERКлиническое значение гипераммониемии при неалкогольной жировой болезни печениClinical significance of hyperammonemia in non-alcoholic fatty liver diseasehttps://orcid.org/0000-0002-1210-2528НадинскаяМ. Ю.NadinskaiaM. Yu.

Надинская Мария Юрьевна - к.м.н., доцент кафедры пропедевтики внутренних болезней, гастроэнтерологии и гепатологии Института клинической медицины имени Н.В. Склифосовского.

119048, Москва, ул. Трубецкая, д. 8, стр. 2

Maria Yu. Nadinskaia - Dr. Sci. (Med.), Associate Professor of the Department of Internal Medicine Propaedeutics, Gastroenterology and Hepatology, Sklifosovskiy Institute of Clinical Medicine.

8, Bldg. 2, Trubetskaya St., Moscow, 119048

nadinskaya_m_yu@staff.sechenov.ruhttps://orcid.org/0000-0003-4294-5531ОковитыйС. В.OkovityiS. V.

Оковитый Сергей Владимирович - д.м.н., профессор, заведующий кафедрой фармакологии и клинической фармакологии, Санкт-Петербургский ГХФУ; профессор Научно-клинического и образовательного центра гастроэнтерологии и гепатологии, Санкт-Петербургский ГУ.

197022, Санкт-Петербург, ул. Профессора Попова, д. 14, лит. А; 199034, Санкт-Петербург, Университетская набережная, д. 7–9

Sergey V. Okovityi - Dr. Sci. (Med.), Professor, Head of the Department of Pharmacology and Clinical Pharmacology, Saint Petersburg SCPU; Professor of the Scientific, Clinical and Educational Center for Gastroenterology and Hepatology, St Petersburg SU.

14A, Professor Popov St., St Petersburg, 197022 7–9, Universitetskaya Emb., St Petersburg, 199034

okovityy@mail.ruhttps://orcid.org/0000-0002-4690-1811ПриходькоВ. А.PrikhodkoV. A.

Приходько Вероника Александровна - к.б.н., доцент кафедры фармакологии и клинической фармакологии.

197022, Санкт-Петербург, ул. Профессора Попова, д. 14, лит. А

Veronika A. Prikhodko - Cand. Sci. (Biol.), Associate Professor of the Department of Pharmacology and Clinical Pharmacology.

14A, Professor Popov St., St Petersburg, 197022

vaprikhodko@mail.ruhttps://orcid.org/0000-0001-7230-0780ШептулинаА. Ф.SheptulinaA. F.

Шептулина Анна Фароковна - к.м.н., ведущий научный сотрудник, руководитель лаборатории экспериментальной и профилактической гастроэнтерологии.

101000, Москва, Петроверигский переулок, д. 10, стр. 3

Anna F. Sheptulina - Cand. Sci. (Med.), Leading Researcher, Head of the Laboratory of Experimental and Preventive Gastroenterology.

10, Bldg. 3, Petroverigsky Lane, Moscow, 101990

asheptulina@gnicpm.ruhttps://orcid.org/0000-0002-3126-141XДееваТ. А.DeevaT. A.

Деева Татьяна Андреевна - к.м.н., доцент кафедры биологической химии Института цифрового биодизайна и искусственного интеллекта в медицине.

119048, Москва, ул. Трубецкая, д. 8, стр. 2

Tatiana A. Deeva - Cand. Sci. (Med.), Associate Professor of the Department of Biological Chemistry, Institute of Digital Biodesign and Artificial Intelligence in Medicine.

8, Bldg. 2, Trubetskaya St., Moscow, 119048

deeva_t_a@staff.sechenov.ruhttps://orcid.org/0000-0001-8913-140XМаевскаяМ. В.MaevskayaM. V.

Маевская Марина Викторовна - д.м.н., профессор, консультант лечебно-диагностического отделения №3 Университетской клинической больницы №2.

119048, Москва, ул. Трубецкая, д. 8, стр. 2

Marina V. Maevskaya - Dr. Sci. (Med.), Professor, Medical Adviser of Diagnostic and Treatment Department No. 3, University Clinical Hospital No. 2.

8, Bldg. 2, Trubetskaya St., Moscow, 119048

mvmaevskaya@me.comhttps://orcid.org/0000-0002-5156-2842ОсипенкоМ. Ф.OsipenkoM. F.

Осипенко Марина Федоровна - д.м.н., профессор, заведующая кафедрой пропедевтики внутренних болезней.

630091, Новосибирск, Красный проспект, д. 52

Marina F. Osipenko - Dr. Sci. (Med.), Professor, Head of the Department of Propedeutics of Internal Medicine.

52, Krasny Ave., Novosibirsk, 630091

ngma@bk.ruПервый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияSechenov First Moscow State Medical University (Sechenov University)Russian FederationСанкт-Петербургский государственный химико-фармацевтический университет; Санкт-Петербургский государственный университетРоссияSaint-Petersburg State Chemical-Pharmaceutical University; St Petersburg State UniversityRussian FederationСанкт-Петербургский государственный химико-фармацевтический университетРоссияSaint-Petersburg State Chemical-Pharmaceutical UniversityRussian FederationНациональный медицинский исследовательский центр терапии и профилактической медициныРоссияNational Medical Research Center for Therapy and Preventive MedicineRussian FederationНовосибирский государственный медицинский университетРоссияNovosibirsk State Medical UniversityRussian Federation20260107202608100112Copyright © Надинская М.Ю., Оковитый С.В., Приходько В.А., Шептулина А.Ф., Деева Т.А., Маевская М.В., Осипенко М.Ф., 20262026Надинская М.Ю., Оковитый С.В., Приходько В.А., Шептулина А.Ф., Деева Т.А., Маевская М.В., Осипенко М.Ф.Nadinskaia M.Y., Okovityi S.V., Prikhodko V.A., Sheptulina A.F., Deeva T.A., Maevskaya M.V., Osipenko M.F.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/10126

В обзоре рассматривается клиническое значение гипераммониемии и гипераммонигистии при неалкогольной (метаболически ассоциированной) жировой болезни печени (НАЖБП). Отмечено, что повышение уровня аммиака может наблюдаться уже на доцирротических стадиях (у 40–78% пациентов) и является не только следствием, но и фактором прогрессирования заболевания, в связи с чем может рассматриваться как самостоятельная патогенетическая мишень. Гипераммониемия усугубляет повреждение гепатоцитов (через нарушение аутофагии и эпигенетическое подавление ферментов орнитинового цикла), способствует развитию саркопении, гепатогенной слабости, когнитивных и иных нейропсихических нарушений, а также ухудшает течение коморбидных состояний. Ключевыми немедикаментозными подходами к коррекции гипераммониемии на фоне НАЖБП являются средиземноморский тип питания с адекватным потреблением белка и регулярная физическая активность с сочетанием аэробных и силовых нагрузок. В качестве патогенетической фармакотерапии обосновано применение L-орнитина L-аспартата (LOLA), который активирует цикл мочевины в печени и глутаминовый шунт в скелетных мышцах, облегчая детоксификацию аммиака. За счет снижения внутриклеточных концентраций аммиака LOLA способствует уменьшению митохондриальной дисфункции, восстановлению процессов аутофагии и замедлению активации звездчатых клеток печени, что может замедлять прогрессирование стеатоза, воспаления и фиброза. Курсовое назначение LOLA в дозах 9–12 г/сут в течение не менее 12 нед. позволяет снизить уровень аммиака, уменьшить стеатоз, улучшить когнитивные функции, повысить переносимость физических нагрузок и качество жизни пациентов. Эксперты подчеркивают, что решение о терапии может приниматься на основании клинических проявлений (гепатогенная слабость, нарушение нейропсихических функций, саркопения) даже без рутинного контроля уровня аммиака в крови. Обзор выполнен в нарративной форме без применения систематического подхода. Проведен целенаправленный поиск источников на русском и английском языках в базах данных PubMed, eLIBRARY.RU, Кокрейновской библиотеке и других электронных ресурсах.

The review discusses the clinical significance of hyperammonemia and hyperammonihistia (tissue ammonia accumulation) in non-alcoholic (metabolic dysfunction-associated) fatty liver disease. Elevated blood and tissue ammonia levels can be observed already at pre-cirrhotic stages (in 40–78% of patients) and are not only a consequence but also a factor of disease progression, making it an independent pathogenetic target. Hyperammonemia exacerbates hepatocellular injury (through impairment of autophagy and epigenetic suppression of enzymes of the ornithine cycle), contributes to the development of sarcopenia, fatigue, cognitive and other neuropsychiatric impairments, and worsens the course of comorbid conditions. Key non-pharmacological approaches include the Mediterranean diet with adequate protein intake and regular physical activity combining aerobic and resistance exercise. From a pathogenetic pharmacotherapy perspective, the use of L-ornithine L-aspartate (LOLA) is justified, as it activates the urea cycle in the liver and the glutamine pathway in skeletal muscle. By reducing intracellular ammonia concentrations, LOLA helps alleviate mitochondrial dysfunction, restore autophagic processes, and slow the activation of hepatic stellate cells, which may in turn slow down the progression of steatosis, inflammation, and fibrosis. Course administration of LOLA at doses of 9–12 g per day for at least 12 weeks has been shown to reduce ammonia levels, decrease steatosis, improve cognitive function, enhance exercise tolerance, and improve patients’ quality of life. The experts emphasize that the decision to initiate therapy may be based on clinical manifestations (hepatogenic weakness, cognitive impairment, sarcopenia), even in the absence of routine monitoring of blood ammonia levels. The review was conducted in a narrative fashion without the use of systematic methodology. A targeted search of Russianand English-language publications was carried out using PubMed, eLIBRARY.RU, the Cochrane Library, and other databases.

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