Rosiglitazone for Nonalcoholic Steatohepatitis: One-Year Results of the Randomized Placebo-Controlled Fatty Liver Improvement With Rosiglitazone Therapy (FLIRT) Trial

Gastroenterology

Volumn 135, Issue 1, 2008, Pages 100-110

  Ratziu, Vlad ^a,e   Giral, Philippe ^c,e   Jacqueminet, Sophie ^a,e   Charlotte, Fréderic ^a,e   Hartemann Heurtier, Agnès ^a,e   Serfaty, Lawrence ^b,e   Podevin, Philippe ^d,e   Lacorte, Jean Marc ^b,e   Bernhardt, Carole ^a,e   Bruckert, Eric ^c,e   Grimaldi, André ^a,e   Poynard, Thierry ^a,e  

^a SORBONNE UNIVERSITÉ   (France)

^b PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^c CENTRE DE RECHERCHE SAINT ANTOINE   (France)

^d HÔPITAL SAINT ANTOINE   (France)

^e CdR Saint Antoine ^*  (France)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPONECTIN; AMINOTRANSFERASE; METFORMIN; PLACEBO; ROSIGLITAZONE; SULFANILAMIDE;

ADULT; AGED; AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; CLINICAL TRIAL; CONGESTIVE HEART FAILURE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISEASE ACTIVITY; DOUBLE BLIND PROCEDURE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; HEADACHE; HEMOGLOBIN BLOOD LEVEL; HUMAN; HUMAN TISSUE; INSULIN RESISTANCE; INSULIN SENSITIVITY; LEG EDEMA; LEG PAIN; LIVER BIOPSY; LIVER FIBROSIS; LIVER NECROSIS; LIVER TOXICITY; MAJOR CLINICAL STUDY; MALAISE; MALE; MUSCLE CRAMP; NAUSEA; NONALCOHOLIC FATTY LIVER; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; TREATMENT OUTCOME; WALKING DIFFICULTY; WEIGHT GAIN;

EID: 46349088361     PISSN: 00165085     EISSN: None     Source Type: Journal    
DOI: 10.1053/j.gastro.2008.03.078     Document Type: Article

References (50)

1. Marchesini G., Bugianesi E., Forlani G., et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 37 (2003) 917-923
2. Ratziu V., and Poynard T. NASH: a hidden and silent fibroser finally revealed?. J Hepatol 42 (2005) 12-14
3. Farrell G.C., and Larter C.Z. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43 (2006) S99-S112
4. Ekstedt M., Franzen L.E., Mathiesen U.L., et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44 (2006) 865-873
5. Adams L.A., Lymp J.F., St Sauver J., et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129 (2005) 113-121
6. Ratziu V., Bonyhay L., Di Martino V., et al. Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis. Hepatology 35 (2002) 1485-1493
7. Sanyal A.J., Banas C., Sargeant C., et al. Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C. Hepatology 43 (2006) 682-689
8. Bugianesi E., Leone N., Vanni E., et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 123 (2002) 134-140
9. Sanyal A.J., Campbell-Sargent C., Mirshahi F., et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 120 (2001) 1183-1192
10. Suzuki A., Lindor K., St Saver J., et al. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol 43 (2005) 1060-1066
11. Foster G.D., Wyatt H.R., Hill J.O., et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med 348 (2003) 2082-2090
12. Skarfors E.T., Wegener T.A., Lithell H., et al. Physical training as treatment for type 2 (non-insulin-dependent) diabetes in elderly men. A feasibility study over 2 years. Diabetologia 30 (1987) 930-933
13. Neuschwander-Tetri B.A., Brunt E.M., Wehmeier K.R., et al. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology 38 (2003) 1008-1017
14. Promrat K., Lutchman G., Uwaifo G.I., et al. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 39 (2004) 188-196
15. Belfort R., Harrison S.A., Brown K., et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 355 (2006) 2297-2307
16. Nair S., Diehl A.M., Wiseman M., et al. Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther 20 (2004) 23-28
17. Ratziu V., Giral P., Charlotte F., et al. Liver fibrosis in overweight patients. Gastroenterology 118 (2000) 1117-1123
18. Kleiner D.E., Brunt E.M., Van Natta M., et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41 (2005) 1313-1321
19. Brunt E.M., Janney C.G., DiBisceglie A.M., et al. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94 (1999) 2467-2474
20. Prati D., Taioli E., Zanella A., et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 137 (2002) 1-10
21. Lutchman G., Modi A., Kleiner D.E., et al. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology 46 (2007) 424-429
22. Friedman S.L., and Bansal M.B. Reversal of hepatic fibrosis-fact or fantasy?. Hepatology 43 (2006) S82-S88
23. Day C.P. Pathogenesis of steatohepatitis. Best Pract Res Clin Gastroenterol 16 (2002) 663-678
24. Miyazaki Y., Mahankali A., Wajcberg E., et al. Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 89 (2004) 4312-4319
25. Iwaki M., Matsuda M., Maeda N., et al. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 52 (2003) 1655-1663
26. Maeda N., Takahashi M., Funahashi T., et al. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50 (2001) 2094-2099
27. Semple R.K., Chatterjee V.K., and O'Rahilly S. PPAR gamma and human metabolic disease. J Clin Invest 116 (2006) 581-589
28. Tiikkainen M., Hakkinen A.M., Korsheninnikova E., et al. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes 53 (2004) 2169-2176
29. Kubota N., Terauchi Y., Kubota T., et al. Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways. J Biol Chem 281 (2006) 8748-8755
30. Dixon J.B., Bhathal P.S., Hughes N.R., et al. Nonalcoholic fatty liver disease: improvement in liver histological analysis with weight loss. Hepatology 39 (2004) 1647-1654
31. Yang S.Q., Lin H.Z., Lane M.D., et al. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci U S A 94 (1997) 2557-2562
32. Lin H.Z., Yang S.Q., Chuckaree C., et al. Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med 6 (2000) 998-1003
33. Ueki K., Kondo T., Tseng Y.H., et al. Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse. Proc Natl Acad Sci U S A 101 (2004) 10422-10427
34. Arkan M.C., Hevener A.L., Greten F.R., et al. IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11 (2005) 191-198
35. Fromenty B., Robin M.A., Igoudjil A., et al. The ins and outs of mitochondrial dysfunction in NASH. Diabetes Metab 30 (2004) 121-138
36. Li Z., Lin H., Yang S., et al. Murine leptin deficiency alters Kupffer cell production of cytokines that regulate the innate immune system. Gastroenterology 123 (2002) 1304-1310
37. Feldstein A.E., Canbay A., Guicciardi M.E., et al. Diet associated hepatic steatosis sensitizes to Fas mediated liver injury in mice. J Hepatol 39 (2003) 978-983
38. Cortez-Pinto H., Chatham J., Chacko V.P., et al. Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study. JAMA 282 (1999) 1659-1664
39. Yki-Jarvinen H. Fat in the liver and insulin resistance. Ann Med 37 (2005) 347-356
40. Samuel V.T., Liu Z.X., Qu X., et al. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 279 (2004) 32345-32353
41. Seppala-Lindroos A., Vehkavaara S., Hakkinen A.M., et al. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 87 (2002) 3023-3028
42. Ryysy L., Hakkinen A.M., Goto T., et al. Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes 49 (2000) 749-758
43. Galli A., Crabb D.W., Ceni E., et al. Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro. Gastroenterology 122 (2002) 1924-1940
44. McCullough A.J. Thiazolidinediones for nonalcoholic steatohepatitis-promising but not ready for prime time. N Engl J Med 355 (2006) 2361-2363
45. Marchesini G., Avagnina S., Barantani E.G., et al. Aminotransferase and gamma-glutamyltranspeptidase levels in obesity are associated with insulin resistance and the metabolic syndrome. J Endocrinol Invest 28 (2005) 333-339
46. Lee D.H., Silventoinen K., Jacobs Jr. D.R., et al. Gamma-glutamyltransferase, obesity, and the risk of type 2 diabetes: observational cohort study among 20,158 middle-aged men and women. J Clin Endocrinol Metab 89 (2004) 5410-5414
47. Nawrocki A.R., Rajala M.W., Tomas E., et al. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 281 (2006) 2654-2660
48. US Food and Drug Administration. FDA briefing document: joint meeting of the Endocrinologic and Metabolic Drug Advisory Committee and the Drug Safety and Risk Management Committee. http://www.fda.gov/ohrms/dockets/ac/07/minutes/2007-4308m1-final.pdf Accessed September 6, 2007
49. Murphy C.E., and Rodgers P.T. Effects of thiazolidinediones on bone loss and fracture. Ann Pharmacother 41 (2007) 2014-2018
50. Lindor K.D., Kowdley K.V., Heathcote E.J., et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 39 (2004) 770-778