medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-374medsovet-7853Research ArticleЗАБОЛЕВАНИЯ БИЛИАРНОЙ СИСТЕМЫ И ПЕЧЕНИDISEASES OF THE BILIARY SYSTEM AND LIVERСаркопения и мальнутриция у пациентов с заболеваниями печениSarcopenia and malnutrition in patients with liver diseaseshttps://orcid.org/0000-0002-9152-1279ОстровскаяА. С.OstrovskayaA. S.

Островская Анна Сергеевна - врач отделения гепатологии Клиники пропедевтики  внутренних болезней, гастроэнтерологии, гепатологии имени В.Х. Василенко.

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Anna S. Ostrovskaya - Doctor of the Hepatology Department of the V.H. Vasilenko, Clinic of Propaedeutics of Internal Diseases, Gastroenterology, Hepatology, Sechenov First Moscow State Medical University (Sechenov University).

8, Bldg. 2, Trubetskaya St., Moscow, 119991

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

Маевская Марина Викторовна - доктор медицинских наук, профессор,  консультант лечебно-диагностического  отделения  №3 Университетской  клинической больницы №2.

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Marina V. Maevskaya - Dr. Sci. (Med.), Professor, Consultant  of Diagnostic and Treatment Department No. 3, Sechenov First Moscow State Medical University (Sechenov University).

8, Bldg. 2, Trubetskaya St., Moscow, 119991

liver.orc@mail.ruПервый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияSechenov First Moscow State Medical University (Sechenov University)Russian Federation2023031120230183542Copyright © Островская А.С., Маевская М.В., 20232023Островская А.С., Маевская М.В.Ostrovskaya A.S., Maevskaya M.V.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/7853

Обзор  посвящен  наиболее  актуальной  информации  по патогенезу, диагностике  и лечению  саркопении  и мальнутриции у пациентов  с заболеваниями печени. Саркопения и мальнутриция – распространенные осложнения  заболеваний печени. Цирроз печени как стадия патологического процесса служит основным предрасполагающим  фактором для развития мальнутриции и саркопении. Частота саркопении при циррозе печени составляет 30–50% и доходит до 100% у декомпенсированных пациентов. Основными патогенетическими звеньями являются: нарушение протеостаза  скелетных мышц, системное воспаление и изменение микробиоты кишечника. За последние годы накоплено достаточно данных для того, чтобы рассматривать эти состояния как прогностически неблагоприятный  фактор у пациентов  с циррозом  печени  различной  этиологии, влияющий на их качество жизни и выживаемость, а также ухудшающий исходы трансплантации. Это диктует необходимость определения унифицированных подходов к диагностике и коррекции данных состояний. В настоящее время для диагностики используются тесты, позволяющие  оценить мышечную силу и функцию. Оценка мышечной массы проводится с применением  инструментальных методов путем измерения отдельных мышц и расчета скелетно-мышечных индексов. У пациентов с циррозом печени и сопутствующей саркопенией  и мальнутрицией с целью коррекции, помимо терапии, направленной  на элиминацию этиологического фактора, применимы стратегии модификации  питания и образа  жизни. Цель обзора  – на основе  литературных данных оценить проблемы диагностики и эффективного лечения недостаточности питания и саркопении у пациентов с заболеваниями печени. В статье представлен обзор основных стратегий к подходу, диагностике и коррекции данных состояний.

This review focuses on the most current  information  on the pathogenesis, diagnosis  and treatment of sarcopenia and malnutrition in patients with liver disease. Sarcopenia  and malnutrition are common complications of liver diseases. Liver cirrhosis, as a stage  of the pathological process, serves as the main predisposing factor for the development of malnutrition and sarcopenia. The frequency  of sarcopenia in liver cirrhosis  is 30–50%  and  reaches  100% in decompensated patients. The main pathogenetic links are: impaired  proteostasis of skeletal  muscles, systemic  inflammation and changes  in gut microbiota. In recent   years, enough   data  have  been  accumulated  to  consider  these   conditions   as  a  prognostically unfavorable   factor in patients with liver cirrhosis of various etiologies,  affecting  their quality of life and survival, as well as worsening  the out-comes  of transplantation. This dictates  the  necessity  to  define  unified  approaches to  diagnostics and  correction  of these conditions. Currently, tests are used for diagnosis, which allow to assess muscle strength and function. Muscle mass is assessed using instrumental methods by measuring  individual  muscles  and calculating skeletal  muscle  indices. In patients with liver cirrhosis and concomitant sarcopenia and malnutrition, nutritional and lifestyle modification  strategies are applicable for correction  in addition  to therapy  aimed at elimination of the etiologic  factor. The aim of the review is to evaluate the problems of diagnosis and effective treatment of malnutrition and sarcopenia in patients with liver disease  based on literature data. The article presents an overview of the main strategies for the approach, diagnosis  and correction  of these  conditions.

недостаточность питанияцирроз печенимышечная массагипераммониемиянутритивный статусmalnutritionliver cirrhosismuscle masshyperammonemianutritional statusReferencesPurnak T, Yilmaz Y. Liver disease and malnutrition. Best Pract Res Clin Gastroenterol. 2013;27(4):619–629. https://doi.org/10.1016/j.bpg.2013.06.018.Purnak T, Yilmaz Y. Liver disease and malnutrition. Best Pract Res Clin Gastroenterol. 2013;27(4):619–629. https://doi.org/10.1016/j.bpg.2013.06.018.ATS, Parkash O, Hashmi SA. Malnutrition and liver disease in a developing country. World J Gastroenterol. 2021;27(30):4985–4998. https://doi.org/10.3748/wjg.v27.i30.4985.ATS, Parkash O, Hashmi SA. Malnutrition and liver disease in a developing country. World J Gastroenterol. 2021;27(30):4985–4998. https://doi.org/10.3748/wjg.v27.i30.4985.Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16–31. https://doi.org/10.1093/ageing/afy169.Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16–31. https://doi.org/10.1093/ageing/afy169.Nishiguchi Sh, Hino K, Moriya K, Shiraki M, Hiramatsu A, Nishikawa H. Assessment criteria for sarcopenia in liver disease (first edition): Report from the working group for creation of sarcopenia assessment criteria in the Japan Society of Hepatology. Kanzo. 2016;57(12):623–633. https://doi.org/10.2957/kanzo.57.623.Nishiguchi Sh, Hino K, Moriya K, Shiraki M, Hiramatsu A, Nishikawa H. Assessment criteria for sarcopenia in liver disease (first edition): Report from the working group for creation of sarcopenia assessment criteria in the Japan Society of Hepatology. Kanzo. 2016;57(12):623–633. https://doi.org/10.2957/kanzo.57.623.Shin S, Jun DW, Saeed WK, Koh DH. A narrative review of malnutrition in chronic liver disease. Ann Transl Med. 2021;9(2):172. https://doi.org/10.21037/atm-20-4868.Shin S, Jun DW, Saeed WK, Koh DH. A narrative review of malnutrition in chronic liver disease. Ann Transl Med. 2021;9(2):172. https://doi.org/10.21037/atm-20-4868.Mazeaud S, Zupo R, Couret A, Panza F, Sardone R, Castellana F. Prevalence of Sarcopenia in Liver Cirrhosis: A Systematic Review and Meta-Analysis. Clin Transl Gastroenterol. 2023;14(7):e00584. https://doi.org/10.14309/ctg.0000000000000584.Mazeaud S, Zupo R, Couret A, Panza F, Sardone R, Castellana F. Prevalence of Sarcopenia in Liver Cirrhosis: A Systematic Review and Meta-Analysis. Clin Transl Gastroenterol. 2023;14(7):e00584. https://doi.org/10.14309/ctg.0000000000000584.Evuri P, Selvi C, Manimekala E, Aravind A, Karunakaran P, Muthukumaran K et al. Study of Prevalence of Sarcopenia in Chronic Liver Disease and its Impact on Outcomes. Int J Innov Res Med Sci. 2022;7(07):335–339. https://doi.org/10.23958/ijirms/vol07-i07/1439.Evuri P, Selvi C, Manimekala E, Aravind A, Karunakaran P, Muthukumaran K et al. Study of Prevalence of Sarcopenia in Chronic Liver Disease and its Impact on Outcomes. Int J Innov Res Med Sci. 2022;7(07):335–339. https://doi.org/10.23958/ijirms/vol07-i07/1439.Nakamura A, Yoshimura T, Sato T, Ichikawa T. Diagnosis and Pathogenesis of Sarcopenia in Chronic Liver Disease Using Liver Magnetic Resonance Imaging. Cureus. 2022;14(5):e24676. https://doi.org/10.7759/cureus.24676.Nakamura A, Yoshimura T, Sato T, Ichikawa T. Diagnosis and Pathogenesis of Sarcopenia in Chronic Liver Disease Using Liver Magnetic Resonance Imaging. Cureus. 2022;14(5):e24676. https://doi.org/10.7759/cureus.24676.Fox R, Stenning K, Slee A, Macnaughtan J, Davies N. Sarcopenia in liver cirrhosis: Prevalence, pathophysiology and therapeutic strategies. Anal Biochem. 2022;647:114581. https://doi.org/10.1016/j.ab.2022.114581.Fox R, Stenning K, Slee A, Macnaughtan J, Davies N. Sarcopenia in liver cirrhosis: Prevalence, pathophysiology and therapeutic strategies. Anal Biochem. 2022;647:114581. https://doi.org/10.1016/j.ab.2022.114581.Topan MM, Sporea I, Dănilă M, Popescu A, Ghiuchici AM, Lupuşoru R, Şirli R. Impact of Sarcopenia on Survival and Clinical Outcomes in Patients With Liver Cirrhosis. Front Nutr. 2021;8:766451. https://doi.org/10.3389/fnut.2021.766451.Topan MM, Sporea I, Dănilă M, Popescu A, Ghiuchici AM, Lupuşoru R, Şirli R. Impact of Sarcopenia on Survival and Clinical Outcomes in Patients With Liver Cirrhosis. Front Nutr. 2021;8:766451. https://doi.org/10.3389/fnut.2021.766451.Nishikawa H, Fukunishi S, Asai A, Nishiguchi S, Higuchi K. Sarcopenia and Frailty in Liver Cirrhosis. Life (Basel). 2021;11(5):399. https://doi.org/10.3390/life11050399.Nishikawa H, Fukunishi S, Asai A, Nishiguchi S, Higuchi K. Sarcopenia and Frailty in Liver Cirrhosis. Life (Basel). 2021;11(5):399. https://doi.org/10.3390/life11050399.Kalafateli M, Mantzoukis K, Choi Yau Y, Mohammad AO, Arora S, Rodrigues S et al. Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the Model for End-stage Liver Disease score. J Cachexia Sarcopenia Muscle. 2017;8(1):113–121. https://doi.org/10.1002/jcsm.12095.Kalafateli M, Mantzoukis K, Choi Yau Y, Mohammad AO, Arora S, Rodrigues S et al. Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the Model for End-stage Liver Disease score. J Cachexia Sarcopenia Muscle. 2017;8(1):113–121. https://doi.org/10.1002/jcsm.12095.Wijarnpreecha K, Werlang M, Panjawatanan P, Kroner PT, Cheungpasitporn W, Lukens FJ et al. Association between sarcopenia and hepatic encephalopathy: A systematic review and meta-analysis. Ann Hepatol. 2020;19(3):245–250. https://doi.org/10.1016/j.aohep.2019.06.007.Wijarnpreecha K, Werlang M, Panjawatanan P, Kroner PT, Cheungpasitporn W, Lukens FJ et al. Association between sarcopenia and hepatic encephalopathy: A systematic review and meta-analysis. Ann Hepatol. 2020;19(3):245–250. https://doi.org/10.1016/j.aohep.2019.06.007.Sam J, Nguyen GC. Protein-calorie malnutrition as a prognostic indicator of mortality among patients hospitalized with cirrhosis and portal hypertension. Liver Int. 2009;29(9):1396–1402. https://doi.org/10.1111/j.1478-3231.2009.02077.x.Sam J, Nguyen GC. Protein-calorie malnutrition as a prognostic indicator of mortality among patients hospitalized with cirrhosis and portal hypertension. Liver Int. 2009;29(9):1396–1402. https://doi.org/10.1111/j.1478-3231.2009.02077.x.Bernal W, Martin-Mateos R, Lipcsey M, Tallis C, Woodsford K, McPhail MJ et al. Aerobic capacity during cardiopulmonary exercise testing and survival with and without liver transplantation for patients with chronic liver disease. Liver Transpl. 2014;20(1):54–62. https://doi.org/10.1002/lt.23766.Bernal W, Martin-Mateos R, Lipcsey M, Tallis C, Woodsford K, McPhail MJ et al. Aerobic capacity during cardiopulmonary exercise testing and survival with and without liver transplantation for patients with chronic liver disease. Liver Transpl. 2014;20(1):54–62. https://doi.org/10.1002/lt.23766.Zeng X, Shi ZW, Yu JJ, Wang LF, Sun CY, Luo YY et al. Skeletal muscle alterations indicate poor prognosis in cirrhotic patients: a multicenter cohort study in China. Hepatol Int. 2023;10.1007/s12072-023-10497-x. https://doi.org/10.1007/s12072-023-10497-x.Zeng X, Shi ZW, Yu JJ, Wang LF, Sun CY, Luo YY et al. Skeletal muscle alterations indicate poor prognosis in cirrhotic patients: a multicenter cohort study in China. Hepatol Int. 2023;10.1007/s12072-023-10497-x. https://doi.org/10.1007/s12072-023-10497-x.Frost RA, Lang CH. Multifaceted role of insulin-like growth factors and mammalian target of rapamycin in skeletal muscle. Endocrinol Metab Clin North Am. 2012;41(2):297–322. https://doi.org/10.1016/j.ecl.2012.04.012.Frost RA, Lang CH. Multifaceted role of insulin-like growth factors and mammalian target of rapamycin in skeletal muscle. Endocrinol Metab Clin North Am. 2012;41(2):297–322. https://doi.org/10.1016/j.ecl.2012.04.012.Castilla-Cortazar I, Prieto J, Urdaneta E, Pascual M, Nuñez M, Zudaire E et al. Impaired intestinal sugar transport in cirrhotic rats: correction by low doses of insulin-like growth factor I. Gastroenterology. 1997;113(4):1180–1187. https://doi.org/10.1053/gast.1997.v113.pm9322513.Castilla-Cortazar I, Prieto J, Urdaneta E, Pascual M, Nuñez M, Zudaire E et al. Impaired intestinal sugar transport in cirrhotic rats: correction by low doses of insulin-like growth factor I. Gastroenterology. 1997;113(4):1180–1187. https://doi.org/10.1053/gast.1997.v113.pm9322513.Gluud C. Serum testosterone concentrations in men with alcoholic cirrhosis: background for variation. Metabolism. 1987;36(4):373–378. https://doi.org/10.1016/0026-0495(87)90210-1.Gluud C. Serum testosterone concentrations in men with alcoholic cirrhosis: background for variation. Metabolism. 1987;36(4):373–378. https://doi.org/10.1016/0026-0495(87)90210-1.Bauer TM, Schwacha H, Steinbrückner B, Brinkmann FE, Ditzen AK, Aponte JJ et al. Small intestinal bacterial overgrowth in human cirrhosis is associated with systemic endotoxemia. Am J Gastroenterol. 2002;97(9):2364–2370. https://doi.org/10.1111/j.1572-0241.2002.05791.x.Bauer TM, Schwacha H, Steinbrückner B, Brinkmann FE, Ditzen AK, Aponte JJ et al. Small intestinal bacterial overgrowth in human cirrhosis is associated with systemic endotoxemia. Am J Gastroenterol. 2002;97(9):2364–2370. https://doi.org/10.1111/j.1572-0241.2002.05791.x.Londhe P, Guttridge DC. Inflammation induced loss of skeletal muscle. Bone. 2015;80:131–142. https://doi.org/10.1016/j.bone.2015.03.015.Londhe P, Guttridge DC. Inflammation induced loss of skeletal muscle. Bone. 2015;80:131–142. https://doi.org/10.1016/j.bone.2015.03.015.Tandon P, Raman M, Mourtzakis M, Merli M. A practical approach to nutritional screening and assessment in cirrhosis. Hepatology. 2017;65(3):1044–1057. https://doi.org/10.1002/hep.29003.Tandon P, Raman M, Mourtzakis M, Merli M. A practical approach to nutritional screening and assessment in cirrhosis. Hepatology. 2017;65(3):1044–1057. https://doi.org/10.1002/hep.29003.Mousa N, Mokhtar A, Neven A, Mahmoud А, Adel I. Nutritional status in cirrhosis; pathogenesis and management. Med J Vir Hepat. 2019;3.2(2):41–47. Available at: https://www.researchgate.net/publication/337351614_Nutritional_status_in_cirrhosis_pathogenesis_and_management.Mousa N, Mokhtar A, Neven A, Mahmoud А, Adel I. Nutritional status in cirrhosis; pathogenesis and management. Med J Vir Hepat. 2019;3.2(2):41–47. Available at: https://www.researchgate.net/publication/337351614_Nutritional_status_in_cirrhosis_pathogenesis_and_management.Nicoletti A, Ponziani FR, Biolato M, Valenza V, Marrone G, Sganga G et al. Intestinal permeability in the pathogenesis of liver damage: From non-alcoholic fatty liver disease to liver transplantation. World J Gastroenterol. 2019;25(33):4814–4834. https://doi.org/10.3748/wjg.v25.i33.4814.Nicoletti A, Ponziani FR, Biolato M, Valenza V, Marrone G, Sganga G et al. Intestinal permeability in the pathogenesis of liver damage: From non-alcoholic fatty liver disease to liver transplantation. World J Gastroenterol. 2019;25(33):4814–4834. https://doi.org/10.3748/wjg.v25.i33.4814.Carson JA, Manolagas SC. Effects of sex steroids on bones and muscles: Similarities, parallels, and putative interactions in health and disease. Bone. 2015;80:67–78. https://doi.org/10.1016/j.bone.2015.04.015.Carson JA, Manolagas SC. Effects of sex steroids on bones and muscles: Similarities, parallels, and putative interactions in health and disease. Bone. 2015;80:67–78. https://doi.org/10.1016/j.bone.2015.04.015.Iizuka K, Machida T, Hirafuji M. Skeletal muscle is an endocrine organ. J Pharmacol Sci. 2014;125(2):125–131. https://doi.org/10.1254/jphs.14r02cp.Iizuka K, Machida T, Hirafuji M. Skeletal muscle is an endocrine organ. J Pharmacol Sci. 2014;125(2):125–131. https://doi.org/10.1254/jphs.14r02cp.Bodine SC. Edward F. Adolph Distinguished Lecture. Skeletal muscle atrophy: Multiple pathways leading to a common outcome. J Appl Physiol (1985). 2020;129(2):272–282. https://doi.org/10.1152/japplphysiol.00381.2020.Bodine SC. Edward F. Adolph Distinguished Lecture. Skeletal muscle atrophy: Multiple pathways leading to a common outcome. J Appl Physiol (1985). 2020;129(2):272–282. https://doi.org/10.1152/japplphysiol.00381.2020.Meyer F, Bannert K, Wiese M, Esau S, Sautter LF, Ehlers L et al. Molecular Mechanism Contributing to Malnutrition and Sarcopenia in Patients with Liver Cirrhosis. Int J Mol Sci. 2020;21(15):5357. https://doi.org/10.3390/ijms21155357.Meyer F, Bannert K, Wiese M, Esau S, Sautter LF, Ehlers L et al. Molecular Mechanism Contributing to Malnutrition and Sarcopenia in Patients with Liver Cirrhosis. Int J Mol Sci. 2020;21(15):5357. https://doi.org/10.3390/ijms21155357.Allen SL, Quinlan JI, Dhaliwal A, Armstrong MJ, Elsharkawy AM, Greig CA et al. Sarcopenia in chronic liver disease: mechanisms and countermeasures. Am J Physiol Gastrointest Liver Physiol. 2021;320(3):G241–G257. https://doi.org/10.1152/ajpgi.00373.2020.Allen SL, Quinlan JI, Dhaliwal A, Armstrong MJ, Elsharkawy AM, Greig CA et al. Sarcopenia in chronic liver disease: mechanisms and countermeasures. Am J Physiol Gastrointest Liver Physiol. 2021;320(3):G241–G257. https://doi.org/10.1152/ajpgi.00373.2020.Henin G, Lanthier N, Dahlqvist G. Pathophysiological changes of the liver-muscle axis in end-stage liver disease: what is the right target? Acta Gastroenterol Belg. 2022;85(4):611–624. https://doi.org/10.51821/85.4.10899.Henin G, Lanthier N, Dahlqvist G. Pathophysiological changes of the liver-muscle axis in end-stage liver disease: what is the right target? Acta Gastroenterol Belg. 2022;85(4):611–624. https://doi.org/10.51821/85.4.10899.Kamimura H, Sato T, Natsui K, Kobayashi T, Yoshida T, Kamimura K et al. Molecular Mechanisms and Treatment of Sarcopenia in Liver Disease: A Review of Current Knowledge. Int J Mol Sci. 2021;22(3):1425. https://doi.org/10.3390/ijms22031425.Kamimura H, Sato T, Natsui K, Kobayashi T, Yoshida T, Kamimura K et al. Molecular Mechanisms and Treatment of Sarcopenia in Liver Disease: A Review of Current Knowledge. Int J Mol Sci. 2021;22(3):1425. https://doi.org/10.3390/ijms22031425.Lai JC, Tandon P, Bernal W, Tapper EB, Ekong U, Dasarathy S, Carey EJ. Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(3):1611–1644. https://doi.org/10.1002/hep.32049.Lai JC, Tandon P, Bernal W, Tapper EB, Ekong U, Dasarathy S, Carey EJ. Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(3):1611–1644. https://doi.org/10.1002/hep.32049.Dasarathy S, Hatzoglou M. Hyperammonemia and proteostasis in cirrhosis. Curr Opin Clin Nutr Metab Care. 2018;21(1):30–36. https://doi.org/10.1097/MCO.0000000000000426.Dasarathy S, Hatzoglou M. Hyperammonemia and proteostasis in cirrhosis. Curr Opin Clin Nutr Metab Care. 2018;21(1):30–36. https://doi.org/10.1097/MCO.0000000000000426.Bunchorntavakul C. Sarcopenia and Frailty in Cirrhosis: Assessment and Management. Med Clin North Am. 2023;107(3):589–604. https://doi.org/10.1016/j.mcna.2022.12.007.Bunchorntavakul C. Sarcopenia and Frailty in Cirrhosis: Assessment and Management. Med Clin North Am. 2023;107(3):589–604. https://doi.org/10.1016/j.mcna.2022.12.007.Keller CW, Fokken C, Turville SG, Lünemann A, Schmidt J, Münz C, Lünemann JD. TNF-alpha induces macroautophagy and regulates MHC class II expression in human skeletal muscle cells. J Biol Chem. 2011;286(5):3970–3980. https://doi.org/10.1074/jbc.M110.159392.Keller CW, Fokken C, Turville SG, Lünemann A, Schmidt J, Münz C, Lünemann JD. TNF-alpha induces macroautophagy and regulates MHC class II expression in human skeletal muscle cells. J Biol Chem. 2011;286(5):3970–3980. https://doi.org/10.1074/jbc.M110.159392.Xia Z, Cholewa J, Zhao Y, Shang HY, Yang YQ, Araújo Pessôa K et al. Targeting Inflammation and Downstream Protein Metabolism in Sarcopenia: A Brief Up-Dated Description of Concurrent Exercise and Leucine-Based Multimodal Intervention. Front Physiol. 2017;8:434. https://doi.org/10.3389/fphys.2017.00434.Xia Z, Cholewa J, Zhao Y, Shang HY, Yang YQ, Araújo Pessôa K et al. Targeting Inflammation and Downstream Protein Metabolism in Sarcopenia: A Brief Up-Dated Description of Concurrent Exercise and Leucine-Based Multimodal Intervention. Front Physiol. 2017;8:434. https://doi.org/10.3389/fphys.2017.00434.Sinclair M, Grossmann M, Gow PJ, Angus PW. Testosterone in men with advanced liver disease: abnormalities and implications. J Gastroenterol Hepatol. 2015;30(2):244–251. https://doi.org/10.1111/jgh.12695.Sinclair M, Grossmann M, Gow PJ, Angus PW. Testosterone in men with advanced liver disease: abnormalities and implications. J Gastroenterol Hepatol. 2015;30(2):244–251. https://doi.org/10.1111/jgh.12695.Shen M, Shi H. Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis. Int J Endocrinol. 2015;2015:294278. https://doi.org/10.1155/2015/294278.Shen M, Shi H. Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis. Int J Endocrinol. 2015;2015:294278. https://doi.org/10.1155/2015/294278.Mowat NA, Edwards CR, Fisher R, McNeilly AS, Green JR, Dawson AM. Hypothalamic-pituitary-gonadal function in men with cirrhosis of the liver. Gut. 1976;17(5):345–350. https://doi.org/10.1136/gut.17.5.345.Mowat NA, Edwards CR, Fisher R, McNeilly AS, Green JR, Dawson AM. Hypothalamic-pituitary-gonadal function in men with cirrhosis of the liver. Gut. 1976;17(5):345–350. https://doi.org/10.1136/gut.17.5.345.Campillo B, Richardet JP, Scherman E, Bories PN. Evaluation of nutritional practice in hospitalized cirrhotic patients: results of a prospective study. Nutrition. 2003;19(6):515–521. https://doi.org/10.1016/s0899-9007(02)01071-7.Campillo B, Richardet JP, Scherman E, Bories PN. Evaluation of nutritional practice in hospitalized cirrhotic patients: results of a prospective study. Nutrition. 2003;19(6):515–521. https://doi.org/10.1016/s0899-9007(02)01071-7.Riggio O, Angeloni S, Ciuffa L, Nicolini G, Attili AF, Albanese C, Merli M. Malnutrition is not related to alterations in energy balance in patients with stable liver cirrhosis. Clin Nutr. 2003;22(6):553–559. https://doi.org/10.1016/s0261-5614(03)00058-x.Riggio O, Angeloni S, Ciuffa L, Nicolini G, Attili AF, Albanese C, Merli M. Malnutrition is not related to alterations in energy balance in patients with stable liver cirrhosis. Clin Nutr. 2003;22(6):553–559. https://doi.org/10.1016/s0261-5614(03)00058-x.Nielsen K, Kondrup J, Martinsen L, Døssing H, Larsson B, Stilling B, Jensen MG. Long-term oral refeeding of patients with cirrhosis of the liver. Br J Nutr. 1995;74(4):557–567. https://doi.org/10.1079/bjn19950158.Nielsen K, Kondrup J, Martinsen L, Døssing H, Larsson B, Stilling B, Jensen MG. Long-term oral refeeding of patients with cirrhosis of the liver. Br J Nutr. 1995;74(4):557–567. https://doi.org/10.1079/bjn19950158.Ивашкин ВТ, Маевская МВ, Жаркова МС, Жигалова СБ, Киценко ЕА, Манукьян ГВ и др. Клинические рекомендации Российского общества по изучению печени и Российской гастроэнтерологической ассоциации по диагностике и лечению фиброза и цирроза печени и их осложнений. Российский журнал гастроэнтерологии, гепатологии, колопрок­ тологии. 2021;31(6):56–102. Режим доступа: https://www.gastro-j.ru/jour/article/view/621/0.Ivashkin VT, Maevskaya MV, Zharkova MS, Zhigalova SB, Kitsenko EA, Manukyan GV et al. Clinical Recommendations of the Russian Scientific Liver Society and Russian Gastroenterological Association on Diagnosis and Treatment of Liver Fibrosis, Cirrhosis and Their Complications. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(6):56–102. (In Russ.) Available at: https://www.gastro-j.ru/jour/article/view/621/0.European Association for the Study of the Liver. Electronic address: easl-office@easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol. 2019;70(1):172–193. https://doi.org/10.1016/j.jhep.2018.06.024.European Association for the Study of the Liver. Electronic address: easl-office@easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol. 2019;70(1):172–193. https://doi.org/10.1016/j.jhep.2018.06.024.Plauth M, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, Bischoff SC. ESPEN guideline on clinical nutrition in liver disease. Clin Nutr. 2019;38(2):485–521. https://doi.org/10.1016/j.clnu.2018.12.022.Plauth M, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, Bischoff SC. ESPEN guideline on clinical nutrition in liver disease. Clin Nutr. 2019;38(2):485–521. https://doi.org/10.1016/j.clnu.2018.12.022.Amodio P, Bemeur C, Butterworth R, Cordoba J, Kato A, Montagnese S et al. The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus. Hepatology. 2013;58(1):325–336. https://doi.org/10.1002/hep.26370.Amodio P, Bemeur C, Butterworth R, Cordoba J, Kato A, Montagnese S et al. The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus. Hepatology. 2013;58(1):325–336. https://doi.org/10.1002/hep.26370.Swart GR, van den Berg JW, van Vuure JK, Rietveld T, Wattimena DL, Frenkel M. Minimum protein requirements in liver cirrhosis determined by nitrogen balance measurements at three levels of protein intake. Clin Nutr. 1989;8(6):329–336. https://doi.org/10.1016/0261-5614(89)90008-3.Swart GR, van den Berg JW, van Vuure JK, Rietveld T, Wattimena DL, Frenkel M. Minimum protein requirements in liver cirrhosis determined by nitrogen balance measurements at three levels of protein intake. Clin Nutr. 1989;8(6):329–336. https://doi.org/10.1016/0261-5614(89)90008-3.Traub J, Reiss L, Aliwa B, Stadlbauer V. Malnutrition in Patients with Liver Cirrhosis. Nutrients. 2021;13(2):540. https://doi.org/10.3390/nu13020540.Traub J, Reiss L, Aliwa B, Stadlbauer V. Malnutrition in Patients with Liver Cirrhosis. Nutrients. 2021;13(2):540. https://doi.org/10.3390/nu13020540.Ney M, Abraldes JG, Ma M, Belland D, Harvey A, Robbins S et al. Insufficient Protein Intake Is Associated With Increased Mortality in 630 Patients With Cirrhosis Awaiting Liver Transplantation. Nutr Clin Pract. 2015;30(4):530–536. https://doi.org/10.1177/0884533614567716.Ney M, Abraldes JG, Ma M, Belland D, Harvey A, Robbins S et al. Insufficient Protein Intake Is Associated With Increased Mortality in 630 Patients With Cirrhosis Awaiting Liver Transplantation. Nutr Clin Pract. 2015;30(4):530–536. https://doi.org/10.1177/0884533614567716.Tsien CD, McCullough AJ, Dasarathy S. Late evening snack: exploiting a period of anabolic opportunity in cirrhosis. J Gastroenterol Hepatol. 2012;27(3):430–441. https://doi.org/10.1111/j.1440-1746.2011.06951.x.Tsien CD, McCullough AJ, Dasarathy S. Late evening snack: exploiting a period of anabolic opportunity in cirrhosis. J Gastroenterol Hepatol. 2012;27(3):430–441. https://doi.org/10.1111/j.1440-1746.2011.06951.x.Vaisman N, Katzman H, Carmiel-Haggai M, Lusthaus M, Niv E. Breakfast improves cognitive function in cirrhotic patients with cognitive impairment. Am J Clin Nutr. 2010;92(1):137–140. https://doi.org/10.3945/ajcn.2010.29211.Vaisman N, Katzman H, Carmiel-Haggai M, Lusthaus M, Niv E. Breakfast improves cognitive function in cirrhotic patients with cognitive impairment. Am J Clin Nutr. 2010;92(1):137–140. https://doi.org/10.3945/ajcn.2010.29211.Kumar A, Davuluri G, Silva RNE, Engelen MPKJ, Ten Have GAM, Prayson R et al. Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis. Hepatology. 2017;65(6):2045–2058. https://doi.org/10.1002/hep.29107.Kumar A, Davuluri G, Silva RNE, Engelen MPKJ, Ten Have GAM, Prayson R et al. Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis. Hepatology. 2017;65(6):2045–2058. https://doi.org/10.1002/hep.29107.Augustyn M, Grys I, Kukla M. Small intestinal bacterial overgrowth and nonalcoholic fatty liver disease. Clin Exp Hepatol. 2019;5(1):1–10. https://doi.org/10.5114/ceh.2019.83151.Augustyn M, Grys I, Kukla M. Small intestinal bacterial overgrowth and nonalcoholic fatty liver disease. Clin Exp Hepatol. 2019;5(1):1–10. https://doi.org/10.5114/ceh.2019.83151.Farrugia MA, Le Garf S, Chierici A, Piche T, Gual P, Iannelli A, Anty R. Therapeutic Physical Exercise Programs in the Context of NASH Cirrhosis and Liver Transplantation: A Systematic Review. Metabolites. 2023;13(3):330. https://doi.org/10.3390/metabo13030330.Farrugia MA, Le Garf S, Chierici A, Piche T, Gual P, Iannelli A, Anty R. Therapeutic Physical Exercise Programs in the Context of NASH Cirrhosis and Liver Transplantation: A Systematic Review. Metabolites. 2023;13(3):330. https://doi.org/10.3390/metabo13030330.Rossi D, D’Avila AF, Galant LH, Marroni CA. Exercise in the physical rehabilitation of cirrotics: a randomized pilot study. Arq Gastroenterol. 2022;59(3):408–413. https://doi.org/10.1590/S0004-2803.202203000-73.Rossi D, D’Avila AF, Galant LH, Marroni CA. Exercise in the physical rehabilitation of cirrotics: a randomized pilot study. Arq Gastroenterol. 2022;59(3):408–413. https://doi.org/10.1590/S0004-2803.202203000-73.Duarte-Rojo A, Ruiz-Margáin A, Montaño-Loza AJ, Macías-Rodríguez RU, Ferrando A, Kim WR. Exercise and physical activity for patients with end-stage liver disease: Improving functional status and sarcopenia while on the transplant waiting list. Liver Transpl. 2018;24(1):122–139. https://doi.org/10.1002/lt.24958.Duarte-Rojo A, Ruiz-Margáin A, Montaño-Loza AJ, Macías-Rodríguez RU, Ferrando A, Kim WR. Exercise and physical activity for patients with end-stage liver disease: Improving functional status and sarcopenia while on the transplant waiting list. Liver Transpl. 2018;24(1):122–139. https://doi.org/10.1002/lt.24958.

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