Silybin combined with phosphatidylcholine and vitamin e in patients with nonalcoholic fatty liver disease: A randomized controlled trial

Free Radical Biology and Medicine

Volumn 52, Issue 9, 2012, Pages 1658-1665

  Loguercio, Carmela ^a   Andreone, Pietro ^b   Brisc, Ciprian ^c   Brisc, Michaela Cristina ^c   Bugianesi, Elisabetta ^d   Chiaramonte, Maria ^e   Cursaro, Carmela ^b   Danila, Mirela ^f   De Sio, Ilario ^a   Floreani, Annarosa ^g   Freni, Maria Antonietta ^h   Grieco, Antonio ⁱ   Groppo, Marzia ^j   Lazzari, Roberta ^g   Lobello, Salvatore ^g   Lorefice, Elisabetta ^k   Margotti, Marzia ^b   Miele, Luca ⁱ   Milani, Stefano ^k   Okolicsanyi, Lajos ^j   Palasciano, Giuseppe ^l   Portincasa, Piero ^l   Saltarelli, Patrizia ^m   Smedile, Antonina ^d   Somalvico, Francesco ⁿ   Spadaro, Aldo ^h   Sporea, Ioan ^f   Sorrentino, Paolo ^o   Vecchione, Raffaela ^o   Tuccillo, Concetta ^a   Blanco, Camillo Del Vecchio ^a   Federico, Alessandro ^a   more..

^a SECOND UNIVERSITY OF NAPLES   (Italy)

^b UNIVERSITY OF BOLOGNA   (Italy)

^c UNIVERSITY OF ORADEA   (Romania)

^d MOLINETTE HOSPITAL   (Italy)

^e SACRO CUORE DON CALABRIA HOSPITAL   (Italy)

^f Gastroenterology and Hepatology   (Romania)

^g Hospital Sant'Antonio   (Italy)

^h Medical Clinic Policlinico Martino   (Italy)

ⁱ CATHOLIC UNIVERSITY   (Italy)

^j Treviso Hospital   (Italy)

^k CAREGGI UNIVERSITY HOSPITAL   (Italy)

^l UNIVERSITY OF BARI   (Italy)

^m UNIVERSITY OF L'AQUILA   (Italy)

ⁿ Society of Statistics   (Italy)

^o UNIVERSITY OF NAPLES FEDERICO II   (Italy)

more..

Author keywords

Antioxidant; Free radicals; Hepatoprotectant; Nonalcoholic fatty liver; Silybin

Indexed keywords

ALANINE AMINOTRANSFERASE; ALPHA TOCOPHEROL PLUS PHOSPHATIDYLCHOLINE PLUS SILYBIN; ANTIOXIDANT; ASPARTATE AMINOTRANSFERASE; FERRITIN; GELATINASE A; INTERLEUKIN 10; PLACEBO; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ARTICLE; BLOOD SAMPLING; BODY MASS; CONTROLLED STUDY; DIARRHEA; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DYSGEUSIA; ECHOGRAPHY; FATTY LIVER; FEMALE; FIBROGENESIS; HEPATITIS C; HEPATITIS C VIRUS; HISTOPATHOLOGY; HUMAN; INSULIN RESISTANCE; LIFESTYLE MODIFICATION; LIVER FIBROSIS; LOW FAT DIET; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NONALCOHOLIC FATTY LIVER; OUTCOME ASSESSMENT; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PRURITUS; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; SCORING SYSTEM; WAIST HIP RATIO;

BODY MASS INDEX; FATTY LIVER; HUMANS; PHOSPHATIDYLCHOLINES; ROMANIA; SILYMARIN; VITAMIN E;

HEPATITIS C VIRUS;

EID: 84858959526     PISSN: 08915849     EISSN: 18734596     Source Type: Journal    
DOI: 10.1016/j.freeradbiomed.2012.02.008     Document Type: Article

References (59)

1. G. Targher, C.P. Day, and E. Bonora Risk of cardiovascular disease in patients with non alcoholic fatty liver disease N. Engl. J. Med. 363 2010 1341 1350
2. A.S. Lok, J.E. Everhart, R.T. Chung, L. Padmanabhan, J.K. Greenson, M.L. Shiffman, G.T. Everson, K.L. Lindsay, H.L. Bonkovsky, A.M. Di Bisceglie, W.M. Lee, T.R. Morgan, M.G. Ghany, C. Morishima HALT-C Trial Group Hepatic steatosis in hepatitis C: comparison of diabetic and non-diabetic patients in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial Clin. Gastroenterol. Hepatol. 5 2007 245 254
3. P. Loria, L.E. Adinolfi, S. Bellentani, E. Bugianesi, A. Grieco, S. Fargion, A. Gasbarrini, C. Loguercio, A. Lonardo, G. Marchesini, F. Marra, M. Persico, D. Prati, and G.S. Baroni NAFLD Expert Committee of the Associazione Italiana per lo Studio del Fegato. Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease: a decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee Dig. Liver Dis. 42 2010 272 282
4. A.J. Sanyal, N. Chalasani, K.V. Kowdley, A. McCullough, A.M. Diehl, N.M. Bass, B.A. Neuschwander-Tetri, J.E. Lavine, J. Tonascia, A. Unalp, M. Van Natta, J. Clark, E.M. Brunt, D.E. Kleiner, J.H. Hoofnagle, P.R. Robuck, and NASH CRN Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis N. Engl. J. Med. 362 2010 1675 1685
5. G. Musso, R. Gambino, M. Cassader, and G. Pagano A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease Hepatology 52 2010 79 104
6. R. Gazak, D. Walterova, and V. Kren Silybin and silymarin - new and emerging applications in medicine Curr. Med. Chem. 14 2007 315 338
7. C. Tamayo, and S. Diamond Review of clinical trials evaluating safety and efficacy of milk thistle (Sylibum marianum [L.] Gaertn.) Integr. Cancer Ther. 6 2007 146 157
8. R. Amini, R. Yazdanparast, S. Aghazadeh, and S.H. Ghaffari Anti-apoptotic and anti-inflammatory effects of Silybum marianum in treatment of experimental steatohepatitis Exp. Toxicol. Pathol. 63 2011 569 574
9. G. Serviddio, F. Bellanti, A.M. Giudetti, G.V. Gnoni, A. Petrella, R. Tamborra, A.D. Romano, T. Rollo, G. Vendemiale, and E. Altomare A silybin-phospholipids complex prevents mitochondrial dysfunction in a rodent model of non-alcoholic steatohepatitis J. Pharmacol. Exp. Ther. 332 2010 922 932
10. A. Di Sario, E. Bendia, S. Taffetani, A. Omenetti, C. Candelaresi, M. Marzioni, S. De Minicis, and A. Benedetti Hepatoprotective and antifibrotic effect of a new silybin-phosphatidylcholine-vitamin E complex in rats Dig. Liver Dis. 37 2005 869 876
11. M. Maghrani, N.A. Zeggwagh, A. Lemhadri, M. El Amraoui, J.B. Michel, and M. Eddouks Study of the hypoglycaemic activity of Fraxinus excelsior and Silybum marianum in an animal model of type 1 diabetes mellitus J. Ethnopharmacol. 91 2004 309 316
12. F. Lirussi, A. Beccarello, G. Zanette, A. De Monte, V. Donadon, M. Velussi, and G. Crepaldi Silybin-β-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease: efficacy study of a new preparation of an anti-oxidant agent Diabetes Nutr. Metab. 15 2002 222 231
13. H.F. Huseini, B. Larijani, R. Heshmat, H. Fakhrzadeh, B. Radjabipour, T. Toliat, and M. Raza The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial Phytother. Res. 20 2006 1036 1039
14. Z. Wen, T.E. Dumas, S.J. Schrieber, R.L. Hawke, M.W. Fried, and P.C. Smith Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract Drug Metab. Dispos. 36 2008 65 72
15. X. Yanyu, S. Yunmei, C. Zhipeng, and P. Qineng The preparation of silybin-phospholipid complex and the study on its pharmacokinetics in rats Int. J. Pharm. 307 2006 77 82
16. L.J. Jia, D.R. Zhang, Z.Y. Li, F.F. Feng, Y.C. Wang, W.T. Dai, C.X. Duan, and Q. Zhang Preparation and characterization of silybin-loaded nanostructured lipid carriers Drug Deliv. 2009 Nov 26 [Epub ahead of print]
17. T.W. Flaig, D.L. Gustafson, L.J. Su, J.A. Zirrolli, F. Crighton, G.S. Harrison, A.S. Pierson, R. Agarwal, and L.M. Glodé A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients Invest. New Drugs 25 2007 139 146
18. P.M. Kidd Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extracts Altern. Med. Rev. 14 2009 226 246
19. C. Loguercio, M. Di Pierro, M.P. Di Marino, A. Federico, D. Disalvo, E. Crafa, C. Tuccillo, F. Baldi, and C. Del Vecchio Blanco Drinking habits of subjects with HCV-related chronic liver disease: the prevalence and effect on clinical, virological and pathological aspects Alcohol Alcohol. 35 2000 296 301
20. K.M. Conigrave, W.D. Hall, and J.B. Saunders The AUDIT questionnaire: choosing a cutoff score. Alcohol Use Disorder Identification Test Addiction 90 1995 1349 1356
21. D.E. Kleiner, E.M. Brunt, M. Van Natta, C. Behling, M.J. Contos, O.W. Cummings, L.D. Ferrell, Y.C. Liu, M.S. Torbenson, A. Unalp-Arida, M. Yeh, A.J. McCullough, and A.J. Sanyal Design and validation of a histological scoring system for nonalcoholic fatty liver disease Hepatology 41 2005 1313 1321
22. S.S. Lee, S.H. Park, H.J. Kim, S.Y. Kim, M.Y. Kim, D.Y. Kim, D.J. Suh, K.M. Kim, M.H. Bae, J.Y. Lee, S.G. Lee, and E.S. Yu Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations J. Hepatol. 52 2010 570 585
23. K. David, K.V. Kowdley, A. Unalp, F. Kanwal, E.M. Brunt, J.B. Schwimmer NASH CRN Research Group Quality of life in adults with nonalcoholic fatty liver disease: baseline data from the nonalcoholic steatohepatitis clinical research network Hepatology 49 2009 1904 1912
24. B.D. Schaan, V.L. Portal, M.T. de Ugarte, A.A. Dias, and D.M. Hatem Emerging risk factors and early atherosclerosis indices in subjects with impaired glucose tolerance Diabetes Metab. 31 2005 581 587
25. H. Tilg, and A.M. Diehl Cytokines in alcoholic and nonalcoholic steatohepatitis N. Engl. J. Med. 343 2000 1467 1476
26. D.S. Manning, and N.H. Afdhal Diagnosis and quantification of fibrosis Gastroenterology 134 2008 1670 1681
27. E.M. Brunt Nonalcoholic steatohepatitis Semin. Liver Dis. 24 2004 3 20
28. K. Ishak, A. Baptista, L. Bianchi, F. Callea, J. De Groote, F. Gudat, H. Denk, V. Desmet, G. Korb, and R.N. MacSween Histological grading and staging of chronic hepatitis J. Hepatol. 22 1995 696 699
29. A. Federico, M. Trappoliere, C. Tuccillo, I. de Sio, A. Di Leva, C. Del Vecchio Blanco, and C. Loguercio A new silybin-vitamin E-phospholipid complex improves insulin resistance and liver damage in patients with non-alcoholic fatty liver disease: preliminary observations Gut 55 2006 901 902
30. C. Loguercio, A. Federico, M. Trappoliere, C. Tuccillo, I. de Sio, A. Di Leva, M. Niosi, M.V. D'Auria, R. Capasso, C. Del Vecchio Blanco Real Sud Group The effect of a silybin-vitamin E-phospholipid complex on nonalcoholic fatty liver disease: a pilot study Dig. Dis. Sci. 52 2007 2387 2395
31. R. Vuppalanchi, and N. Chalasani Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: selected practical issues in their evaluation and management Hepatology 49 2009 306 317
32. E.R. Miller III, R. Pastor-Barriuso, D. Dalal, R.A. Riemersma, L.J. Appel, and E. Guallar Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality Ann. Intern. Med. 142 2005 37 46
33. L.B. Seeff Are herbals as safe as their advocates believe? J. Hepatol. 50 2009 13 16
34. M. Trappoliere, A. Caligiuri, M. Schmid, C. Bertolani, P. Failli, F. Vizzutti, E. Novo, C. di Manzano, F. Marra, C. Loguercio, and M. Pinzani Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells J. Hepatol. 50 2009 1102 1111
35. J.W. Wu, L.C. Lin, and T.H. Tsai Drug-drug interactions of silymarin on the perspective of pharmacokinetics J. Ethnopharmacol. 12 2009 185 193
36. C. Loguercio, T. De Simone, M.V. D'Auria, I. de Sio, A. Federico, C. Tuccillo, A.M. Abbatecola, C. Del Vecchio Blanco Italian AISF Clinical Group Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver Dig. Liver Dis. 36 2004 398 405
37. M.C. Devers, S. Campbell, J. Shaw, P. Zimmet, and D. Simmons Should liver function tests be included in definitions of metabolic syndrome? Evidence from the association between liver function tests, components of metabolic syndrome and prevalent cardiovascular disease Diabet. Med. 25 2008 523 529
38. L. Castera, and M. Pinzani Biopsy and non-invasive methods for the diagnosis of liver fibrosis: does it take two to tango? Gut 59 2010 861 866
39. Y. Popov, and D. Schuppan Targeting liver fibrosis: strategies for development and validation of antifibrotic therapies Hepatology 50 2009 1294 1306
40. D.G. Tiniakos, M.B. Vos, and E.M. Brunt Nonalcoholic fatty liver disease: pathology and pathogenesis Annu. Rev. Pathol. 5 2010 145 171
41. C.H. Hung, J.H. Wang, T.H. Hu, C.H. Chen, K.C. Chang, Y.H. Yen, Y.H. Kuo, M.C. Tsai, S.N. Lu, and C.M. Lee Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection World J. Gastroenterol. 16 2010 2265 2271
42. L.B. Seeff, T.M. Curto, G. Szabo, G.T. Everson, H.L. Bonkovsky, J.L. Dienstag, M.L. Shiffman, K.L. Lindsay, A.S. Lok, A.M. Di Bisceglie, W.M. Lee, M.G. Ghany HALT-C Trial Group Herbal product use by persons enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial Hepatology 47 2008 605 612
43. S.J. Polyak, C. Morishima, M.C. Shuhart, C.C. Wang, Y. Liu, and D.Y. Lee Inhibition of T-cell inflammatory cytokines, hepatocyte NF-κB signaling, and HCV infection by standardized silymarin Gastroenterology 132 2007 1925 1936
44. P. Ferenci, T.M. Scherzer, H. Kerschner, K. Rutter, S. Beinhardt, H. Hofer, M. Schöniger-Hekele, H. Holzmann, and P. Steindl-Munda Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy Gastroenterology 135 2008 1561 1567
45. M. Biermer, and T. Berg Rapid suppression of hepatitis C viremia induced by intravenous silibinin plus ribavirin Gastroenterology 137 2009 390 391
46. A. Ahmed-Belkacem, N. Ahnou, L. Barbotte, C. Wychowski, C. Pallier, R. Brillet, R.T. Pohl, and J.M. Pawlotsky Silibinin and related compounds are direct inhibitors of hepatitis C virus RNA-dependent RNA polymerase Gastroenterology 138 2010 1112 1122
47. F. Stickel, and D. Shuppan Herbal medicine in the treatment of liver diseases Dig. Liver Dis. 39 2007 293 304
48. B.P. Jacobs, C. Dennehy, G. Ramirez, J. Sapp, and V.A. Lawrence Milk thistle for the treatment of liver disease: a systematic review and meta-analysis Am. J. Med. 113 2002 506 515
49. A. Rambaldi, B.P. Jacobs, G. Iaquinto, and C. Gluud Milk thistle for alcoholic and/or hepatitis B or C liver diseases - a systematic Cochrane Hepato-Biliary Group review with meta-analyses of randomized clinical trials Am. J. Gastroenterol. 100 2005 2583 2591
50. V. Simánek, V. Kren, J. Ulrichová, J. Vicar, and L. Cvak Silymarin: what is in the name...? An appeal for a change of editorial policy Hepatology 32 2000 442 444
51. C. Loguercio, and D. Festi Silybin and the liver: from basic research to clinical practice World J. Gastroenterol. 17 2011 2288 2301
52. S. Aghazadeh, and R. Yazdanparast Inhibition of JNK along with activation of ERK1/2 MAPK pathways improve steatohepatitis among the rats Clin. Nutr. 29 2010 381 385
53. Y. Ikura, M. Ohsawa, T. Suekane, H. Fukushima, H. Itabe, H. Jomura, S. Nishiguchi, T. Inoue, T. Naruko, S. Ehara, N. Kawada, T. Arakawa, and M. Ueda Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: impact on disease progression Hepatology 43 2006 506 514
54. K.K. Kharbanda, M.E. Mailliard, C.R. Baldwin, H.C. Beckenhauer, M.F. Sorrell, and D.J. Tuma Betaine attenuates alcoholic steatosis by restoring phosphatidylcholine generation via the phosphatidylethanolamine methyltransferase pathway J. Hepatol. 46 2007 314 321
55. C.P. Colturato, R.P. Constantin, A.S. Maeda Jr., R.P. Constantin, N.S. Yamamoto, A. Bracht, E.L. Ishii-Iwamoto, and J. Constantin Metabolic effects of silibinin in the rat liver Chem. Biol. Interact. 195 2012 119 132
56. J. Yao, M. Zhi, and C. Minhu Effect of silybin on high-fat-induced fatty liver in rats Braz. J. Med. Biol. Res. 44 2011 652 659
57. F. Salamone, F. Galvano, A. Marino, C. Paternostro, D. Tibullo, F. Bucchieri, A. Mangiameli, M. Parola, E. Bugianesi, and G. Li Volti Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis Dig. Liver Dis. 2011 Dec 23 [Epub ahead of print]
58. G. Li Volti, S. Salomone, V. Sorrenti, A. Mangiameli, V. Urso, I. Siarkos, F. Galvano, and F. Salamone Effect of silibinin on endothelial dysfunction and ADMA levels in obese diabetic mice Cardiovasc. Diabetol. 10 2011 62
59. M. Mehrab-Mohseni, H. Sendi, N. Steuerwald, S. Ghosh, L.W. Schrum, and H.L. Bonkovsky Legalon-SIL downregulates HCV core and NS5A in human hepatocytes expressing full-length HCV World J. Gastroenterol. 17 2011 1694 1700