Фармакотерапия неалкогольной жировой болезни печени: акцент на фиброз

Стаценко М.Е., Туркина С.В., Шилина Н.Н. и др. Фармакотерапия неалкогольной жировой болезни печени: акцент на фиброз. Consilium Medicum. 2018; 20 (8): 37–41. DOI: 10.26442/2075-1753_2018.8.37-41

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Statsenko M.E., Turkina S.V., Shilina N.N. et al. Nonalcoholic fatty liver disease pharmacotherapy: accent on fibrosis. Consilium Medicum. 2018; 20 (8): 37–41. DOI: 10.26442/2075-1753_2018.8.37-41

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Аннотация

Цель исследования – оценка влияния таурина на выраженность фиброза печени, структурные и функциональные параметры печени у пациентов с неалкогольной жировой болезнью печени (НАЖБП).

Материалы и методы исследования. Проведено проспективное сравнительное рандомизированное исследование, в которое были включены 60 пациентов с НАЖБП, диагностированной по данным оценки ультразвукового исследования печени (на аппарате SIEMENS SONOLINE G50, Германия, с допплеровским датчиком с оценкой эхогенности печеночной паренхимы, сосудистого рисунка, степени затухания эхосигнала) и индексом фиброза печени NFS>0, 675 (F3–4 fibrosis). Методом простой рандомизации пациенты были распределены на 2 группы: 1-я (основная) – пациенты с НАЖБП, которые принимали препарат таурин в суточной дозе 1000 мг (двукратный прием по 500 мг/сут) дополнительно к базисной терапии сопутствующих заболеваний (сахарный диабет 2-го типа, ишемическая болезнь сердца, артериальная гипертензия); 2-я (контрольная) – пациенты с НАЖБП принимали только препараты базисной терапии сопутствующих заболеваний. Исходно и через 24 нед проводимой терапии исследовалось содержание коллагена IV типа в крови, рассчитывались индекс стеатоза печени FLI и индекc фиброза NFS. Состояние углеводного обмена контролировали по уровню глюкозы крови натощак, определяли базальный инсулин и рассчитывали индекс инсулинорезистентности HOMA-IR. Для контроля состояния липидного обмена крови определяли уровни общего холестерина, триглицеридов, липопротеидов низкой плотности, липопротеидов высокой плотности. Для оценки маркеров повреждения и функционального состояния печени изучали активность аланиновой и аспарагиновой аминотрансферазы, g-глутамилтранспептидазы.

Результаты. По окончании 24-недельной терапии таурином у пациентов с НАЖБП и фиброзом печени отмечены статистически значимое снижение коллагена IV типа, снижение индекса фиброза NFS на всех стадиях фиброзных изменений, статистически значимое – на ранних стадиях фиброза (NFS≤0,675). Выявлена выраженная метаболическая активность препарата, проявляющаяся гипогликемизирующим, липидснижающим эффектами, а также возможностью достоверного снижения выраженности инсулинорезистентности.

Ключевые слова: неалкогольная жировая болезнь печени, таурин, индекс фиброза печени, коллаген IV типа, структурные и функциональные показатели.

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Study objective – to evaluate taurin effect on liver fibrosis severity, structural and functional liver characteristics in patients with nonalcoholic fatty liver disease (NAFLD).

Materials and methods. The prospective comparative randomized study included 60 patients with NAFLD diagnosed according to liver ultrasound results (using SIEMENS SONOLINE G50, Germany system with doppler sensor for liver parenchymal echogenicity, vascular pattern, and echoed signal decrement evaluation) and liver fibrosis index NFS>0.675 (F3–4 fibrosis). With the use of simple randomization patients were divided into 2 groups: group 1 (study group) included patients with NAFLD who received taurin in total daily dose 1000 mg (500 mg twice a day) in addition to comorbid conditions (diabetes mellitus type 2, ischemic heart disease, hypertension) treatment; group 2 (control group) included patients with NAFLD who received only comorbid conditions treatment. Type IV collagen serum level, fatty liver index (FLI), and NAFLD fibrosis score (NFS) were evaluated at baseline and after 24 weeks of treatment. Сarbohydrate metabolism parameters were monitored by fasting plasma glucose level, basal insulin level and insulin resistance index (HOMA-IR) evaluation. For lipid metabolism monitoring total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein levels were evaluated. For damage and functional liver markers assessment alanine and aspartate aminotransferase, g-glutamyl transpeptidase activity was evaluated.
Results. After 24 weeks of treatment with taurin a statistically significant decrease in type IV collagen level, and NFS decrease on all stages of fibrotic changes that was statistically significant on early fibrosis stages (NFS≤0.675) were observed in patients with NAFLD and liver fibrosis. A significant metabolic activity of the drug was shown that presented with hypoglycemic and lipid-lowering effects as well as significant insulin resistance reduction.

Key words: nonalcoholic fatty liver disease, taurin, liver fibrosis score, type IV collagen, structural and functional characteristics.

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Список литературы

1. Younossi ZM, Koenig AB, Abdelatif D et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64: 73–84.

2. Ивашкин В.Т., Драпкина О.М., Маев И.В. и др. Распространенность неалкогольной жировой болезни печени у пациентов амбулаторно-поликлиническоий практики в Российской̆ Федерации: результаты исследования DIREG 2. РЖГГК. 2015; 6: 31–42. / Ivashkin V.T., Drapkina O.M., Maev I.V. i dr. Rasprostranennost nealkogolnoĭ zhirovoĭ bolezni pecheni u pacientov ambulatorno-poliklinicheskoĭ praktiki v Rossiĭskoĭ Federacii: rezultaty issledovaniya DIREG 2. RZhGGK. 2015; 6: 31–42. [in Russian]
3. Patil R, Sood GK. Non-alcoholic fatty liver disease and cardiovascular risk. World J Gastrointest Pathophysiol 2017; 8 (2): 51–8.
4. Arulanandan A, Ang B, Bettencourt R et al. Association Between Quantity of Liver Fat and Cardiovascular Risk in Patients With Nonalcoholic Fatty Liver Disease Independent of Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol 2015; 13: 1513–20.
5. Sö̈derberg C, Stȧl P, Askling J et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 2010; 51: 595–602.
6. Sinn DH, Kang D, Jang HR et al. Development of chronic kidney disease in patients with non-alcoholic fatty liver disease: A cohort study. J Hepatol 2017; 67 (6): 274–1280.
7. Lonardo A, Ballestri S, Guaraldi G et al. Fatty liver is associated with an increased risk of diabetes and cardiovascular disease – Evidence from three different disease models: NAFLD, HCV and HIV. World J Gastroenterol 2016; 22 (44): 9674–93.
8. Ekstedt M, Hagstrom H, Nasr P et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 2015; 61: 1547–54.
9. Hagström H, Nasr P, Ekstedt M et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol 2017; 67 (6): 1265–73.
10. EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. European Association for the Study of the Liver (EASL) & European Association for the Study of Diabetes (EASD) & European Association for the Study of Obesity (EASO). Diabetologia 2016; 59: 1121–40.
11. Weiskirchen R. Hepatoprotective and Anti-fibrotic Agents: It’s Time to Take the Next Step. Front Pharmacol 2015; 6: 303–43.
12. Schaffer SW, Azuma J, Mozaffari M. Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 2009; 87 (2): 91–9.
13. Barua M, Liu Y, Quinn MR. Taurine chloramine inhibits inducible nitric oxide synthase and TNF-alpha gene expression in activated alveolar macrophages: decreased NF-kappaB activation and IkappaB kinase activity. J Immunol 2001; 167 (4): 2275–81.
14. Li M, Reynolds CM, Sloboda DM et al. Effects of Taurine Supplementation on Hepatic Markers of Inflammation and Lipid Metabolism in Mothers and Offspring in the Setting of Maternal Obesity. PLoS One 2013; 8 (10): e769.
15. Abdel-Moneim AM, Al-Kahtani MA, El-Kersh MA, Al-Omair MA. Free Radical- Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage. PLoS One 2015; 10 (12): e0144509.
16. De la Puerta C, Arrieta FJ, Balsa JA et al. Taurine and glucose metabolism: a review. Nutr Hosp 2010; 25: 910–9.
17. Militante JD, Lombardini JB. Dietary taurine supplementation: hypolipidemic and antiatherogenic effects. Nutr Res 2004; 24: 787–801.
18. Putnam K, Shoemaker R, Yiannikouris F, Cassis LA. The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. Am J Physiol Heart Circ Physiol 2012; 30: H1219–1230.
19. Нano T, Kasano M, Tomari H, Iwane N. Taurine suppresses pressor response through the inhibition of sympathetic nerve activity and the improvement in baro-reflex sensitivity of spontaneously hypertensive rats. Adv Exp Med Biol 2009; 643: 57–63.
20. Ergü̈n Yílmaz. The diagnostic role of ultrasonograhyy in liver streatosis. Turkish J Gastroenterol 1999; 2: 96–100.
21. Angulo P, Hui JM, Marchesini G et al. The NAFLD Fibrosis Score: A Noninvasive System That Identifies Liver Fibrosis in Patients with NAFLD. Hеpatology 2007; 45 (4): 846–54.
22. Bedogni G, Bellentani S, Miglioli L et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterology 2006; 6: 33–8.
23. Стаценко М.Е., Туркина С.В., Шилина Н.Н. Поражение печени у больных с хронической сердечной недостаточностью ишемического генеза и сахарным диабетом типа 2 – коварный тандем: возможности дополнительной органопротективной терапии. Consilium Medicum. 2016; 18 (5): 103–9. / Stacenko M.E., Turkina S.V., Shilina N.N. Porazhenie pecheni u bolnyh s hronicheskoj serdechnoj nedostatochnostyu ishemicheskogo geneza i saharnym diabetom tipa 2 – kovarnyj tandem: vozmozhnosti dopolnitelnoj organoprotektivnoj terapii. Consilium Medicum. 2016; 18 (5): 103–9. [in Russian].
24. Morling JR, Fallowfield JA, Williamson RM et al. y-Glutamyltransferase, but not markers of hepatic fibrosis, is associated with cardiovascular disease in older people with type 2 diabetes mellitus: the Edinburgh Type 2 Diabetes Study. Diabetologia 2015; 58: 1484–93.
25. Gentile CL, Nivala AM, Gonzales JC et al. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease. Am J Regul Integr Comp Physiol. 2011; 301 (6): 1710–22.

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1. Younossi ZM, Koenig AB, Abdelatif D et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64: 73–84.
2. Ivashkin V.T., Drapkina O.M., Maev I.V. i dr. Rasprostranennost nealkogolnoĭ zhirovoĭ bolezni pecheni u pacientov ambulatorno-poliklinicheskoĭ praktiki v Rossiĭskoĭ Federacii: rezultaty issledovaniya DIREG 2. RZhGGK. 2015; 6: 31–42. [in Russian]
3. Patil R, Sood GK. Non-alcoholic fatty liver disease and cardiovascular risk. World J Gastrointest Pathophysiol 2017; 8 (2): 51–8.
4. Arulanandan A, Ang B, Bettencourt R et al. Association Between Quantity of Liver Fat and Cardiovascular Risk in Patients With Nonalcoholic Fatty Liver Disease Independent of Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol 2015; 13: 1513–20.
5. Sö̈derberg C, Stȧl P, Askling J et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 2010; 51: 595–602.
6. Sinn DH, Kang D, Jang HR et al. Development of chronic kidney disease in patients with non-alcoholic fatty liver disease: A cohort study. J Hepatol 2017; 67 (6): 274–1280.
7. Lonardo A, Ballestri S, Guaraldi G et al. Fatty liver is associated with an increased risk of diabetes and cardiovascular disease – Evidence from three different disease models: NAFLD, HCV and HIV. World J Gastroenterol 2016; 22 (44): 9674–93.
8. Ekstedt M, Hagstrom H, Nasr P et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 2015; 61: 1547–54.
9. Hagström H, Nasr P, Ekstedt M et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol 2017; 67 (6): 1265–73.
10. EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. European Association for the Study of the Liver (EASL) & European Association for the Study of Diabetes (EASD) & European Association for the Study of Obesity (EASO). Diabetologia 2016; 59: 1121–40.
11. Weiskirchen R. Hepatoprotective and Anti-fibrotic Agents: It’s Time to Take the Next Step. Front Pharmacol 2015; 6: 303–43.
12. Schaffer SW, Azuma J, Mozaffari M. Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 2009; 87 (2): 91–9.
13. Barua M, Liu Y, Quinn MR. Taurine chloramine inhibits inducible nitric oxide synthase and TNF-alpha gene expression in activated alveolar macrophages: decreased NF-kappaB activation and IkappaB kinase activity. J Immunol 2001; 167 (4): 2275–81.
14. Li M, Reynolds CM, Sloboda DM et al. Effects of Taurine Supplementation on Hepatic Markers of Inflammation and Lipid Metabolism in Mothers and Offspring in the Setting of Maternal Obesity. PLoS One 2013; 8 (10): e769.
15. Abdel-Moneim AM, Al-Kahtani MA, El-Kersh MA, Al-Omair MA. Free Radical- Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage. PLoS One 2015; 10 (12): e0144509.
16. De la Puerta C, Arrieta FJ, Balsa JA et al. Taurine and glucose metabolism: a review. Nutr Hosp 2010; 25: 910–9.
17. Militante JD, Lombardini JB. Dietary taurine supplementation: hypolipidemic and antiatherogenic effects. Nutr Res 2004; 24: 787–801.
18. Putnam K, Shoemaker R, Yiannikouris F, Cassis LA. The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. Am J Physiol Heart Circ Physiol 2012; 30: H1219–1230.
19. Нano T, Kasano M, Tomari H, Iwane N. Taurine suppresses pressor response through the inhibition of sympathetic nerve activity and the improvement in baro-reflex sensitivity of spontaneously hypertensive rats. Adv Exp Med Biol 2009; 643: 57–63.
20. Ergü̈n Yílmaz. The diagnostic role of ultrasonograhyy in liver streatosis. Turkish J Gastroenterol 1999; 2: 96–100.
21. Angulo P, Hui JM, Marchesini G et al. The NAFLD Fibrosis Score: A Noninvasive System That Identifies Liver Fibrosis in Patients with NAFLD. Hеpatology 2007; 45 (4): 846–54.
22. Bedogni G, Bellentani S, Miglioli L et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterology 2006; 6: 33–8.
23. Stacenko M.E., Turkina S.V., Shilina N.N. Porazhenie pecheni u bolnyh s hronicheskoj serdechnoj nedostatochnostyu ishemicheskogo geneza i saharnym diabetom tipa 2 – kovarnyj tandem: vozmozhnosti dopolnitelnoj organoprotektivnoj terapii. Consilium Medicum. 2016; 18 (5): 103–9. [in Russian].
24. Morling JR, Fallowfield JA, Williamson RM et al. y-Glutamyltransferase, but not markers of hepatic fibrosis, is associated with cardiovascular disease in older people with type 2 diabetes mellitus: the Edinburgh Type 2 Diabetes Study. Diabetologia 2015; 58: 1484–93.
25. Gentile CL, Nivala AM, Gonzales JC et al. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease. Am J Regul Integr Comp Physiol. 2011; 301 (6): 1710–22.

Авторы

М.Е.Стаценко*, С.В.Туркина, Н.Н.Шилина, Е.Е.Горбачева, А.А.Ермоленко

ФГБОУ ВО «Волгоградский государственный медицинский университет» Минздрава России. 400131, Россия, Волгоград, пл. Павших Борцов, д. 1
*mestatsenko@rambler.ru

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M.E.Statsenko*, S.V.Turkina, N.N.Shilina, E.E.Gorbachev, A.A.Ermolenko

Volgograd State Medical University of Ministry of Health of the Russian Federation. 400131, Russian Federation, Volgograd, pl. Pavshikh Bortsov, d. 1

*mestatsenko@rambler.ru

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