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Невирусные заболевания печени: патогенетические подходы к терапии

https://doi.org/10.33667/2078-5631-2019-2-20(395)-30-36

Полный текст:

Аннотация

Алкогольная болезнь печени и неалкогольная жировая болезнь печени — хронические неинфекционные заболевания с крайне высокой распространенностью среди населения Земли. В настоящее время прослеживается тенденция к стремительному росту их количества с нередкой инвалидизацией больных и высокой потребностью в трансплантации печени. Нарушения основных обменных процессов в печени под влиянием экзогенных и эндогенных факторов являются отправной точкой в развитии алкогольной и неалкогольной патологии печени. В данном обзоре рассмотрены основные рекомендации по немедикаментозной и медикаментозной тактике ведения больных с заболеваниями печени невирусной этиологии с детальной характеристикой основных гепатопротекторов с акцентом на универсальные свойства силимарина.

Об авторах

М. А. Осадчук
ФГАОУ ВО «Первый Московский государственный медицинский университет имени И. М. Сеченова (Сеченовский университет)» Минздрава России
Россия

д. м. н., проф., зав. кафедрой поликлинической терапии института клинической медицины, заслуженный деятель науки России

г. Москва



Е. Д. Миронова
ФГАОУ ВО «Первый Московский государственный медицинский университет имени И. М. Сеченова (Сеченовский университет)» Минздрава России
Россия

врач-ординатор, кафедра поликлинической терапии института клинической медицины 

г. Москва



Список литературы

1. Younossi ZM, Blissett D, Blissett R, et al. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. // Hepatology. 2016; 64 (5): 1577–1586.

2. Gao B, Bataller R. Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets. // Gastroenterology. 2011; 141 (5): 1572–1585.

3. Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. // Lancet. 2009; 373 (9682): 2223–2233.

4. Yousaf S, Patel R. Alcoholic Liver Disease. — Treasure Island (FL): StatPearls Publishing.; 2019.

5. Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. // Gastroenterology. 2015; 148 (3): 547–555.

6. Alcohol–Related Disease Impact. Accessed September 22, 2019. Available from: nccd.cdc.gov/DPH_ARDI/default/default.aspx.

7. Milić S, Lulić D, Štimac D. Non–alcoholic fatty liver disease and obesity: Biochemical, metabolic and clinical presentations. // World J Gastroenterol. 2014; 20 (28): 9330–9337.

8. Firneisz G. Non–alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age? // World J Gastroenterol. 2014; 20 (27): 9072–9089.

9. Allen AM, Therneau TM, Larson JJ, Coward A, Somers VK, Kamath PS. Nonalcoholic Fatty Liver Disease Incidence and Impact on Metabolic Burden and Death: a 20 Year-Community Study. // Hepatology. 2018; 67 (5): 1726–1736.

10. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non–alcoholic fatty liver disease and non–alcoholic steatohepatitis in adults. // Aliment Pharmacol Ther. 2011; 34 (3): 274–285.

11. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease — Meta-analytic assessment of prevalence, incidence, and outcomes. // Hepatology. 2016; 64 (1): 73–84.

12. Ashtari S, Pourhoseingholi MA, Zali MR. Non–alcohol fatty liver disease in Asia: Prevention and planning. // World J Hepatol. 2015; 7 (13): 1788–1796.

13. Dajani A, AbuHammour A. Treatment of Non-alcoholic Fatty Liver Disease: Where do we Stand? An Overview. // Saudi J Gastroenterol. 2016; 22 (2): 91–105.

14. Ивашкин В.Т., Драпкина О. М., Маев И. В. и др. Распространенность неалкогольной жировой болезни печени у пациентов амбулаторной практики в Российской Федерации: результаты исследования DIREG 2. // Российский журнал гастроэнтерологии, гепатологии, колопроктологии 2015; 25: 31–8.

15. Sanyal AJ, Brunt EM, Kleiner DE, et al. Endpoints and clinical trial design for nonalcoholic steatohepatitis. // Hepatology. 2011; 54 (1): 344–353.

16. Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. // Hepatology. 2006; 44 (4): 865–873.

17. Milić S, Stimac D. Nonalcoholic fatty liver disease/steatohepatitis: epidemiology, pathogenesis, clinical presentation and treatment. // Dig Dis. 2012; 30 (2): 158–162.

18. Poynard T, Mathurin P, Lai C–L, et al. A comparison of fibrosis progression in chronic liver diseases. // J Hepatol. 2003; 38 (3): 257–265.

19. White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. // Clin Gastroenterol Hepatol. 2012; 10 (12): 1342–1359.e2.

20. Mittal S, El–Serag HB, Sada YH, et al. Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease. // Clin Gastroenterol Hepatol. 2016; 14 (1): 124–131.e1.

21. Charlton MR, Burns JM, Pedersen RA, Watt KD, Heimbach JK, Dierkhising RA. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. // Gastroenterology. 2011; 141 (4): 1249–1253.

22. Nascimbeni F, Pais R, Bellentani S, et al. From NAFLD in clinical practice to answers from guidelines. // J Hepatol. 2013; 59 (4): 859–871.

23. Review Team, LaBrecque DR, Abbas Z, et al. World Gastroenterology Organisation global guidelines: Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. // J Clin Gastroenterol. 2014; 48 (6): 467–473.

24. Mazo DF, Malta FM, Stefano JT, et al. Validation of PNPLA3 polymorphisms as risk factor for NAFLD and liver fibrosis in an admixed population. // Ann Hepatol. 2019; 18 (3): 466–471.

25. Grimaudo S, Pipitone RM, Pennisi G, et al. Association Between PNPLA3 rs738409 C>G Variant and Liver-Related Outcomes in Patients with Non-alcoholic Fatty Liver Disease. // Clin Gastroenterol Hepatol. August 2019.

26. Karoli R, Fatima J, Singh PS, et al. Association of Genetic Non-alcoholic Fatty Liver Disease with Insulin Resistance–Are we Different? // J Assoc Physicians India. 2019; 67 (3): 34–38.

27. Ahmed F, Baloch Q, Memon ZA, Ali I. An observational study on the association of nonalcoholic fatty liver disease and metabolic syndrome with gall stone disease requiring cholecystectomy. // Ann Med Surg (Lond). 2017; 17: 7–13.

28. Kratzer W, Kächele V, Mason RA, et al. Gallstone prevalence in relation to smoking, alcohol, coffee consumption, and nutrition. The Ulm Gallstone Study. // Scand J Gastroenterol. 1997; 32 (9): 953–958.

29. Amigo L, Zanlungo S, Mendoza H, Miquel JF, Nervi F. Risk factors and pathogenesis of cholesterol gallstones: state of the art. // Eur Rev Med Pharmacol Sci. 1999; 3 (6): 241–246.

30. Vakhrushev YM, Lukashevich АР, Penkina IA, Suchkova EV. Comparative analysis of bile acid spectrum in non–alcoholic fatty liver disease and cholelithiasis. // Ter Arkh. 2019; 91 (2): 48–51.

31. Maev IV, Samsonov AA, Palgova LK, Pavlov CS, Shirokova E, Starostin KM. Real-world comorbidities and treatment patterns among patients with non-alcoholic fatty liver disease receiving phosphatidylcholine as adjunctive therapy in Russia. // BMJ Open Gastroenterol. 2019; 6 (1).

32. Zhang H-J, He J, Pan L–L, et al. Effects of Moderate and Vigorous Exercise on Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial. // JAMA Intern Med. 2016; 176 (8): 1074–1082.

33. Cho J-Y, Chung T-H, Lim K-M, Park H-J, Jang J-M. The impact of weight changes on nonalcoholic Fatty liver disease in adult men with normal weight. // Korean J Fam Med. 2014; 35 (5): 243–250.

34. Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. // J Hepatol. 2017; 67 (4): 829–846.

35. Zelber–Sagi S, Kessler A, Brazowsky E, et al. A double–blind randomized placebo–controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. // Clin Gastroenterol Hepatol. 2006; 4 (5): 639–644.

36. European Medicine Agency. Xenical 120 mg Summary of Product Characteristics. Accessed September 22, 2019. Available from: www.ema.europa.eu/docs/en_GB/document_library/EPAR-Product_Information/human/000154/WC500058428.pdf.

37. Corey KE, Vuppalanchi R. Assessment and management of comorbidities (including cardiovascular disease) in patients with nonalcoholic fatty liver disease. // Clin Liver Dis (Hoboken). 2012; 1 (4): 114–116.

38. Loomba R, Lutchman G, Kleiner DE, et al. Clinical trial: pilot study of metformin for the treatment of non–alcoholic steatohepatitis. // Aliment Pharmacol Ther. 2009; 29 (2): 172–182.

39. Ballestri S, Lonardo A, Bonapace S, Byrne CD, Loria P, Targher G. Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease. // World J Gastroenterol. 2014; 20 (7): 1724–1745.

40. Del Ben M, Baratta F, Polimeni L, Angelico F. Non-alcoholic fatty liver disease and cardiovascular disease: epidemiological, clinical and pathophysiological evidences. // Intern Emerg Med. 2012; 7 Suppl 3: S 291–296.

41. Oni ET, Agatston AS, Blaha MJ, et al. A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? // Atherosclerosis. 2013; 230 (2): 258–267.

42. Patti G, Cannon CP, Murphy SA, et al. Clinical benefit of statin pretreatment in patients undergoing percutaneous coronary intervention: a collaborative patient-level meta-analysis of 13 randomized studies. // Circulation. 2011; 123 (15): 1622–1632.

43. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. // Cochrane Database Syst Rev. 2013; (1): CD 004816.

44. Nseir W, Mahamid M. Statins in nonalcoholic fatty liver disease and steatohepatitis: updated review. // Curr Atheroscler Rep. 2013; 15 (3): 305.

45. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non–alcoholic fatty liver disease: Practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. // Am J Gastroenterol. 2012; 107 (6): 811–826.

46. Foster T, Budoff MJ, Saab S, Ahmadi N, Gordon C, Guerci AD. Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease: the St Francis Heart Study randomized clinical trial. // Am J Gastroenterol. 2011; 106 (1): 71–77.

47. Chang CY, Schiano TD. Review article: drug hepatotoxicity. // Aliment Pharmacol Ther. 2007; 25 (10): 1135–1151.

48. Gazzerro P, Proto MC, Gangemi G, et al. Pharmacological actions of statins: a critical appraisal in the management of cancer. // Pharmacol Rev. 2012; 64 (1): 102–146.

49. Kugelmas M, Hill DB, Vivian B, Marsano L, McClain CJ. Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. // Hepatology. 2003; 38 (2): 413–419.

50. Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. // Am J Gastroenterol. 2003; 98 (11): 2485–2490.

51. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. // N Engl J Med. 2010; 362 (18): 1675–1685.

52. Shu X, Zhang L, Ji G. Vitamin E Therapy in Non–Alcoholic Fatty Liver Disease. // IJCM. 2014; 05 (03): 87–92.

53. Ali AH, Carey EJ, Lindor KD. Recent advances in the development of farnesoid X receptor agonists. // Ann Transl Med. 2015; 3 (1): 5.

54. Mudaliar S, Henry RR, Sanyal AJ, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. // Gastroenterology. 2013; 145 (3): 574–582.e1.

55. Lewis JD, Ferrara A, Peng T, et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. // Diabetes Care. 2011; 34 (4): 916–922.

56. Fialla AD, Israelsen M, Hamberg O, Krag A, Gluud LL. Nutritional therapy in cirrhosis or alcoholic hepatitis: a systematic review and meta– analysis. // Liver Int. 2015; 35 (9): 2072–2078.

57. Mathurin P, O’Grady J, Carithers RL, et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta– analysis of individual patient data. // Gut. 2011; 60 (2): 255–260.

58. Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. // N Engl J Med. 2009; 360 (26): 2758–2769.

59. Chen CM, Yoon Y–H, Yi H, Lucas DL. Alcohol and hepatitis C mortality among males and females in the United States: a life table analysis. // Alcohol Clin Exp Res. 2007; 31 (2): 285–292.

60. Befrits R, Hedman M, Blomquist L, et al. Chronic hepatitis C in alcoholic patients: prevalence, genotypes, and correlation to liver disease. // Scand J Gastroenterol. 1995; 30 (11): 1113–1118.

61. Donato F, Tagger A, Chiesa R, et al. Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: a case-control study in Italy. Brescia HCC Study. // Hepatology. 1997; 26 (3): 579–584.

62. Hutchinson SJ, Bird SM, Goldberg DJ. Influence of alcohol on the progression of hepatitis C virus infection: a meta-analysis. // Clin Gastroenterol Hepatol. 2005; 3 (11): 1150–1159.

63. Mendenhall C, Roselle GA, Gartside P, Moritz T. Relationship of protein calorie malnutrition to alcoholic liver disease: a reexamination of data from two Veterans Administration Cooperative Studies. // Alcohol Clin Exp Res. 1995; 19 (3): 635–641.

64. Huisman EJ, Trip EJ, Siersema PD, van Hoek B, van Erpecum KJ. Protein energy malnutrition predicts complications in liver cirrhosis. // Eur J Gastroenterol Hepatol. 2011; 23 (11): 982–989.

65. Plauth M, Cabré E, Riggio O, et al. ESPEN Guidelines on Enteral Nutrition: Liver disease. // Clin Nutr. 2006; 25 (2): 285–294.

66. Dey A, Cederbaum AI. Alcohol and oxidative liver injury. // Hepatology. 2006; 43 (2 Suppl 1): S 63–74.

67. Nguyen T–H, Jacobs P, Hanrahan A, et al. Health care costs of persons with newly diagnosed hepatitis C virus: a population–based, observational study. // J Viral Hepat. 2008; 15 (9): 634–640.

68. Stewart S, Prince M, Bassendine M, et al. A randomized trial of antioxidant therapy alone or with corticosteroids in acute alcoholic hepatitis. // J Hepatol. 2007; 47 (2): 277–283.

69. Seo YS, Shah VH. The role of gut–liver axis in the pathogenesis of liver cirrhosis and portal hypertension. // Clin Mol Hepatol. 2012; 18 (4): 337–346.

70. Kirpich IA, Solovieva NV, Leikhter SN, et al. Probiotics restore bowel flora and improve liver enzymes in human alcohol–induced liver injury: a pilot study. // Alcohol. 2008; 42 (8): 675–682.

71. Zhao HY, Wang HJ, Lu Z, Xu SZ. Intestinal microflora in patients with liver cirrhosis. // Chin J Dig Dis. 2004; 5 (2): 64–67.

72. Vlachogiannakos J, Saveriadis AS, Viazis N, et al. Intestinal decontamination improves liver haemodynamics in patients with alcohol–related decompensated cirrhosis. // Aliment Pharmacol Ther. 2009; 29 (9): 992–999.

73. Aurich H, Sgodda M, Kaltwasser P, et al. Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. // Gut. 2009; 58 (4): 570–581.

74. Jang YO, Kim YJ, Baik SK, et al. Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: a pilot study. // Liver Int. 2014; 34 (1): 33–41.

75. Terai S, Ishikawa T, Omori K, et al. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. // Stem Cells. 2006; 24 (10): 2292–2298.

76. Akiyama K, Chen C, Wang D, et al. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. // Cell Stem Cell. 2012; 10 (5): 544–555.

77. Kuo TK, Hung S-P, Chuang C–H, et al. Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells. // Gastroenterology. 2008; 134 (7): 2111–2121, 2121.e1–3.

78. Ismail A, Fouad O, Abdelnasser A, Chowdhury A, Selim A. Stem cell therapy improves the outcome of liver resection in cirrhotics. // J Gastrointest Cancer. 2010; 41 (1): 17–23.

79. Yao J, Zhi M, Gao X, Hu P, Li C, Yang X. Effect and the probable mechanisms of silibinin in regulating insulin resistance in the liver of rats with non–alcoholic fatty liver. // Braz J Med Biol Res. 2013; 46 (3): 270–277.

80. Ni X, Wang H. Silymarin attenuated hepatic steatosis through regulation of lipid metabolism and oxidative stress in a mouse model of nonalcoholic fatty liver disease (NAFLD). // Am J Transl Res. 2016; 8 (2): 1073–1081.

81. Polyak SJ, Morishima C, Lohmann V, et al. Identification of hepatoprotective flavonolignans from silymarin. // Proc Natl Acad Sci USA. 2010; 107 (13): 5995–5999.

82. Saliou C, Valacchi G, Rimbach G. Assessing bioflavonoids as regulators of NF-kappa B activity and inflammatory gene expression in mammalian cells. // Meth Enzymol. 2001; 335: 380–387.

83. Yoo HG, Jung SN, Hwang YS, et al. Involvement of NF-kappaB and caspases in silibinin-induced apoptosis of endothelial cells. // Int J Mol Med. 2004; 13 (1): 81–86.

84. Saller R, Melzer J, Reichling J, Brignoli R, Meier R. An updated systematic review of the pharmacology of silymarin. // Forsch Komplementmed. 2007; 14 (2): 70–80.

85. Lorenz D, Mennicke WH. [Elimination of drugs in cholecystectomized patients. Studies with silymarin in patients with extrahepatic complications]. Methods Find // Exp Clin Pharmacol. 1981; 3 Suppl 1: 103–106S.

86. Schandalik R, Gatti G, Perucca E. Pharmacokinetics of silybin in bile following administration of silipide and silymarin in cholecystectomy patients. // Arzneimittelforschung. 1992; 42 (7): 964–968.

87. Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. // Am J Gastroenterol. 1998; 93 (2): 139–143.

88. Loguercio C, Federico A, Trappoliere M, et al. The effect of a silybin — vitamin E-phospholipid complex on nonalcoholic fatty liver disease: a pilot study. // Dig Dis Sci. 2007; 52 (9): 2387–2395.

89. Nencini C, Giorgi G, Micheli L. Protective effect of silymarin on oxidative stress in rat brain. // Phytomedicine. 2007; 14 (2–3): 129–135.

90. Clichici S, Olteanu D, Nagy A-L, Oros A, Filip A, Mircea PA. Silymarin inhibits the progression of fibrosis in the early stages of liver injury in CCl-treated rats. // J Med Food. 2015; 18 (3): 290–298.

91. Stanca E, Serviddio G, Bellanti F, Vendemiale G, Siculella L, Giudetti AM. Down-regulation of LPCAT expression increases platelet-activating factor level in cirrhotic rat liver: potential antiinflammatory effect of silybin. // Biochim Biophys Acta. 2013; 1832 (12): 2019–2026.

92. Hermann R, von Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. // Planta Med. 2012; 78 (13): 1458–1477.

93. Federico A, Dallio M, Loguercio C. Silymarin/ Silybin and Chronic Liver Disease: A Marriage of Many Years. // Molecules. 2017; 22 (2).


Для цитирования:


Осадчук М.А., Миронова Е.Д. Невирусные заболевания печени: патогенетические подходы к терапии. Медицинский алфавит. 2019;3(20):30-36. https://doi.org/10.33667/2078-5631-2019-2-20(395)-30-36

For citation:


Osadchuk M.A., Mironova E.D. Non-viral liver diseases: pathogenetic approaches to therapy. Medical alphabet. 2019;3(20):30-36. (In Russ.) https://doi.org/10.33667/2078-5631-2019-2-20(395)-30-36

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