Abstract Chronic liver disease (CLD), manifested as hepatic injury, is a major cause of global morbidity and mortality. CLD progresses to fibrosis, cirrhosis, and—ultimately—hepatocellular carcinoma (HCC) if left untreated. The different phenotypes of CLD based on their respective clinical features and causative agents include alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD), and drug-induced liver injury (DILI). The preferred treatment modality for CLD includes lifestyle modification and diet, along with limited pharmacological agents for symptomatic treatment. Moreover, oxidative stress (OS) is an important pathological mechanism underlying all CLD phenotypes; hence, the use of antioxidants to manage the disease is justified. Based on available clinical evidence, silymarin can be utilized as a hepatoprotective agent, given its potent antioxidant, antifibrotic, and anti-inflammatory properties. The role of silymarin in suppressing OS has been well established, and therefore silymarin is recommended for use in ALD and NAFLD in the guidelines approved by the Russian Medical Scientific Society of Therapists and the Gastroenterology Scientific Society of Russia. However, to discuss the positioning of the original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies, an expert panel of international and Russian medical professionals was convened on 11 November 2020. The panel reviewed approaches for the prevention and treatment of OS, existing guidelines for patient management for CLD, and available evidence on the effectiveness of silymarin in reducing OS, fibrosis, and hepatic inflammation and presented in the form of a narrative review. Key messages An expert panel of international and Russian medical professionals reviewed existing guidelines for ALD, NAFLD, MAFLD, and DILI to establish consensus recommendations that oxidative stress is the common pathophysiological mechanism underlying these conditions. The panel also discussed the positioning of original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies. The panel reviewed the effectiveness of 140 mg original silymarin three times a day in reducing oxidative stress in chronic liver diseases such as ALD, NAFLD, MAFLD, and DILI.

https://www.tandfonline.com/doi/pdf/10.1080/07853890.2022.2069854?needAccess=true

Role of silymarin as antioxidant in clinical management of chronic liver diseases: a narrative review

Study Objective: to identify the risk factors of drug-induced liver involvement in first trimester of pregnancy. Study Design: prospective randomized comparative clinical research.

/pdf/risk-factors-of-drug-induced-liver-involvement-in-first-1rfwwwtp7g.pdf

Risk Factors of Drug-Induced Liver Involvement in First Trimester of Pregnancy

1Research Center of Medical Genetics, Mocow; 2V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Mocow; 3I.M. Sechenov First Moscow State Medical University, Moscow; 4Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk, Russia Муковисцидоз (МВ) в 10% случаев осложняется циррозом печени (ЦП). ЦП при МВ относится к билиарным циррозам, прогрессирует за счет нарастания симптомов портальной гипертензии и гиперспленизма и стоит на 3-м месте среди причин смерти при МВ. Целью исследования было изучить распространенность и особенности ЦП с портальной гипертензией при МВ у детей и подростков в России и на примерах историй болезни больных, перенесших трансплантацию печени, оценить риски при трансплантации и после нее, а также особенности течения послеоперационного периода. Материалы и методы исследования: исследование проведено на основе данных регистра больных МВ Российской Федерации (РФ) за 2014 год и анализа историй болезни 4 пациентов, находившихся под наблюдением специалистов научно-клинического отдела муковисцидоза ФГБНУ «Медико-генетический научный центра» и ФГБУ «ФНЦ трансплантологии и искусственных органов им. В.И. Шумакова». Результаты: установлена частота ЦП с портальной гипертензией в РФ – 3,66% от общего числа больных и 47,85% всех больных с ЦП. В 1,5 раза чаще ЦП встречался у лиц мужского пола – 49 (62,82%). Медиана возраста постановки диагноза в группе пациентов с ЦП, как и количество умерших, были достоверно выше, чем в группе без поражения печени. Показана связь ЦП с низким нутритивным статусом, развитием грамотрицательной инфекции, сахарным диабетом, остеопорозом, кровохарканьем. Заключение: при обследовании больных с ЦП неясной этиологии в диагностический поиск должны быть включены проведение потовой пробы и ДНК-диагностика наиболее частых мутаций гена CFTR. Дети и взрослые больные МВ с ЦП с признаками портальной гипертензии должны наблюдаться совместно с транплантологами. Ключевые слова: муковисцидоз, цирроз печени, портальная гипертензия, гиперспленизм, трансплантация печени. Цит.: Е.И. Кондратьева, О.М. Цирульникова, А.Ю. Воронкова, О.И. Маломуж, Н.А. Ильенкова, Н.Ю. Каширская, В.Д. Шерман. Цирроз и опыт трансплантации печени у детей и подростков при муковисцидозе. Педиатрия. 2017; 96 (6): 36–47.

Cirrhosis and liver transplantation experience in children and adolescents with cystic fibrosis

Among drug-induced liver injuries (DILI), the cholestatic type is second in frequency (from 20 to 40%), the most common is the hepatocellular variant (up to 78%). For this reason, practitioners of various specialties, including neurologists and psychiatrists, do not monitor cholestasis parameters, and drug-induced liver injury with cholestasis (DILIС) remains unrecognized. The urgency of this problem is great, because the frequency of deaths in DILIС is only slightly lower than t in the hepatocellular type; in addition, it DILIС is much more likely to become persistent increasing the risk of chronic liver injury.Among the drugs used in neurology and psychiatry, the “leaders” in terms of the number of DILIС are antidepressants, both tricyclic (amitriptyline, imipramine) and selective serotonin reuptake inhibitors (SSRIs: paroxetine, sertraline, fluoxetine, citalopram, escitalopram), antidepressants), antipsychotics (chlorpromazine, fluphenazine), anticonvulsants (mainly carbamazepine).If the patient has a history of DILI caused by any of the forementioned medications, the agent should be switched to another drug from the same group with a minimal risk of DILI. If there is a history of DILI associated with antidepressants, it is recommended to choose SSRIs. It is necessary to monitor not only the activity of transaminases and bilirubin, but also the cholestasis parameters (alkaline phosphatase, γ-glutamyl transpeptidase) during treatment. 

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Drug-induced liver injury with cholestasis in the neurologist and psychiatric practice

Modern therapy of any oncohematological disease involves the development of hepatotoxicity

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O the question of the terms of prescribing hepatoprotector drugs in children with hemoblastosis

Research of the etiological structure of acute hepatitis of unknown origin has allowed verifying the hepatitis E at 5,6% cases, DNA EBV was found out at 2,8% cases and 2,8% of patients had RNA HGV in blood. The data of the anamnesis and a clinical and laboratory picture does not allow excluding at 31% of patients a drug-induced liver injury.

https://cyberleninka.ru/article/n/lekarstvennye-porazheniya-pecheni-v-strukture-ostrogo-gepatita-neutochnennoy-etiologii.pdf

Н. Д. Ющук

Papers

Лекарственные поражения печени в структуре острого гепатита неуточненной этиологии