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    Ariel Feldstein

    TitleProfessor
    SchoolUniversity of California, San Diego
    DepartmentPediatrics
    Address9500 Gilman Drive #0984
    CA La Jolla 92093
    Phone858-966-8907
    vCardDownload vCard

      Collapse Research 
      Collapse Research Activities and Funding
      Sterile inflammation and pyroptotic cell death in liver fibrosis
      NIH/NIDDK R01DK113592Mar 1, 2017 - Feb 28, 2022
      Role: Principal Investigator
      Encapsulated RNAs in extracellular vesicles contribute ALD progression
      NIH/NIAAA R21AA023574Sep 5, 2015 - Aug 31, 2017
      Role: Principal Investigator
      Oxidized Metabolites of Linoleic Acid in Alcohol-induced Liver Injury
      NIH/NIAAA U01AA022489Sep 1, 2014 - Jun 30, 2019
      Role: Principal Investigator
      Alcoholic liver disease: Biochemical, cellular and systemic responses to ethanol
      NIH P20AA017837Sep 30, 2009 - Aug 31, 2014
      Role: Co-Investigator
      Caspase Dependent Cell Death in Nonalcoholic Fatty Liver Disease
      NIH/NIDDK R01DK082451Aug 24, 2009 - Jun 30, 2013
      Role: Principal Investigator
      The Lysosomal-Mitochondrial Axis in Nonalcoholic Fatty Liver Disease
      NIH/NIDDK R01DK076852Mar 1, 2007 - Jan 31, 2013
      Role: Principal Investigator

      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Wree A, Inzaugarat ME, Feldstein A. Tmbim 1, a novel anti-inflammatory approach for NASH treatment. Hepatology. 2017 Aug 31. PMID: 28859227.
        View in: PubMed
      2. Cabrera D, Wree A, Povero D, Solís N, Hernandez A, Pizarro M, Moshage H, Torres J, Feldstein A, Cabello-Verrugio C, Brandan E, Barrera F, Arab JP, Arrese M. Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis. Sci Rep. 2017 Jun 14; 7(1):3491. PMID: 28615649.
        View in: PubMed
      3. Alegre F, Pelegrin P, Feldstein A. Inflammasomes in Liver Fibrosis. Semin Liver Dis. 2017 May; 37(2):119-127. PMID: 28564720.
        View in: PubMed
      4. Tricò D, Di Sessa A, Caprio S, Chalasani N, Liu W, Liang T, Graf J, Herzog RI, Johnson CD, Umano GR, Feldstein A, Santoro N. Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota? Antioxid Redox Signal. 2017 Apr 07. PMID: 28279074.
        View in: PubMed
      5. Mann JP, Feldstein A, Nobili V. Update on lipid species and paediatric nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care. 2017 Mar; 20(2):110-116. PMID: 27906700.
        View in: PubMed
      6. Cannito S, Morello E, Bocca C, Foglia B, Benetti E, Novo E, Chiazza F, Rogazzo M, Fantozzi R, Povero D, Sutti S, Bugianesi E, Feldstein A, Albano E, Collino M, Parola M. Microvesicles released from fat-laden cells promote activation of hepatocellular NLRP3 inflammasome: A pro-inflammatory link between lipotoxicity and non-alcoholic steatohepatitis. PLoS One. 2017; 12(3):e0172575. PMID: 28249038.
        View in: PubMed
      7. Mridha AR, Wree A, Robertson AA, Yeh MM, Johnson CD, Van Rooyen DM, Haczeyni F, Teoh NC, Savard C, Ioannou GN, Masters SL, Schroder K, Cooper MA, Feldstein A, Farrell GC. "NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice". J Hepatol. 2017 Feb 03. PMID: 28167322.
        View in: PubMed
      8. Alkhouri N, Feldstein A. Treating Nonalcoholic Steatohepatitis (NASH) in Children: Not a Cinch Task. Hepatology. 2017 Jan 10. PMID: 28073147.
        View in: PubMed
      9. Nobili V, Feldstein A. Fatty liver in adolescents: Mechanisms, clinical features and therapy. J Hepatol. 2016 Oct 11. PMID: 27742132.
        View in: PubMed
      10. Eguchi A, Lazaro RG, Wang J, Kim J, Povero D, Willliams B, Ho SB, Stärkel P, Schnabl B, Ohno-Machado L, Tsukamoto H, Feldstein A. Extracellular vesicles released by hepatocytes from gastric infusion model of ALD contain a miRNA barcode that can be detected in blood. Hepatology. 2016 Sep 17. PMID: 27639178.
        View in: PubMed
      11. Eguchi A, Lazic M, Armando AM, Phillips SA, Katebian R, Maraka S, Quehenberger O, Sears DD, Feldstein A. Circulating adipocyte-derived extracellular vesicles are novel markers of metabolic stress. J Mol Med (Berl). 2016 Nov; 94(11):1241-1253. PMID: 27394413.
        View in: PubMed
      12. Inzaugarat ME, Wree A, Feldstein A. Hepatocyte mitochondrial DNA released in microparticles and toll-like receptor 9 activation: A link between lipotoxicity and inflammation during nonalcoholic steatohepatitis. Hepatology. 2016 Aug; 64(2):669-71. PMID: 27239763.
        View in: PubMed
      13. Smathers RL, Chiang DJ, McMullen MR, Feldstein A, Roychowdhury S, Nagy LE. Soluble IgM links apoptosis to complement activation in early alcoholic liver disease in mice. Mol Immunol. 2016 Apr; 72:9-18. PMID: 26922040.
        View in: PubMed
      14. Wree A, Mehal WZ, Feldstein A. Targeting Cell Death and Sterile Inflammation Loop for the Treatment of Nonalcoholic Steatohepatitis. Semin Liver Dis. 2016 Feb; 36(1):27-36. PMID: 26870930.
        View in: PubMed
      15. Arrese M, Cabrera D, Kalergis AM, Feldstein A. Innate Immunity and Inflammation in NAFLD/NASH. Dig Dis Sci. 2016 May; 61(5):1294-303. PMID: 26841783.
        View in: PubMed
      16. Alkhouri N, Feldstein A. Noninvasive diagnosis of nonalcoholic fatty liver disease: Are we there yet? Metabolism. 2016 Aug; 65(8):1087-95. PMID: 26972222.
        View in: PubMed
      17. Povero D, Feldstein A. Novel Molecular Mechanisms in the Development of Non-Alcoholic Steatohepatitis. Diabetes Metab J. 2016 Feb; 40(1):1-11. PMID: 26912150.
        View in: PubMed
      18. Crespo M, Lappe S, Feldstein A, Alkhouri N. Similarities and differences between pediatric and adult nonalcoholic fatty liver disease. Metabolism. 2016 Aug; 65(8):1161-71. PMID: 26961580.
        View in: PubMed
      19. Goffredo M, Caprio S, Feldstein A, D'Adamo E, Shaw MM, Pierpont B, Savoye M, Zhao H, Bale AE, Santoro N. Role of TM6SF2 rs58542926 in the pathogenesis of nonalcoholic pediatric fatty liver disease: A multiethnic study. Hepatology. 2016 Jan; 63(1):117-25. PMID: 26457389.
        View in: PubMed
      20. Eguchi A, De Mollerat Du Jeu X, Johnson CD, Nektaria A, Feldstein A. Liver Bid suppression for treatment of fibrosis associated with non-alcoholic steatohepatitis. J Hepatol. 2016 Mar; 64(3):699-707. PMID: 26555271.
        View in: PubMed
      21. Povero D, Panera N, Eguchi A, Johnson CD, Papouchado BG, de Araujo Horcel L, Pinatel EM, Alisi A, Nobili V, Feldstein A. Lipid-induced hepatocyte-derived extracellular vesicles regulate hepatic stellate cell via microRNAs targeting PPAR-?. Cell Mol Gastroenterol Hepatol. 2015 Nov 1; 1(6):646-663.e4. PMID: 26783552.
        View in: PubMed
      22. Kathemann S, Bechmann LP, Sowa JP, Manka P, Dechêne A, Gerner P, Lainka E, Hoyer PF, Feldstein A, Canbay A. Etiology, outcome and prognostic factors of childhood acute liver failure in a German Single Center. Ann Hepatol. 2015 Sep-Oct; 14(5):722-8. PMID: 26256901.
        View in: PubMed
      23. Pan JJ, Fisher-Hoch SP, Chen C, Feldstein A, McCormick JB, Rahbar MH, Beretta L, Fallon MB. Burden of nonalcoholic fatty liver disease and advanced fibrosis in a Texas Hispanic community cohort. World J Hepatol. 2015 Jun 18; 7(11):1586-94. PMID: 26085918.
        View in: PubMed
      24. Eguchi A, Yoshitomi T, Lazic M, Johnson CD, Vong LB, Wree A, Povero D, Papouchado BG, Nagasaki Y, Feldstein A. Redox nanoparticles as a novel treatment approach for inflammation and fibrosis associated with nonalcoholic steatohepatitis. Nanomedicine (Lond). 2015 May 28; 1-12. PMID: 26020857.
        View in: PubMed
      25. Nagpal SJ, Lopez R, Feldstein A, Alkhouri N. Serum cytokeratin-18 fragment levels predict development of type 2 diabetes mellitus in adult patients with NAFLD. Liver Int. 2015 Dec; 35(12):2621. PMID: 25939859.
        View in: PubMed
      26. Wree A, Johnson CD, Font-Burgada J, Eguchi A, Povero D, Karin M, Feldstein A. Hepatocyte-specific Bid depletion reduces tumor development by suppressing inflammation-related compensatory proliferation. Cell Death Differ. 2015 Dec; 22(12):1985-94. PMID: 25909884.
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      27. Eguchi A, Mulya A, Lazic M, Radhakrishnan D, Berk MP, Povero D, Gornicka A, Feldstein A. Microparticles release by adipocytes act as "find-me" signals to promote macrophage migration. PLoS One. 2015; 10(4):e0123110. PMID: 25849214.
        View in: PubMed
      28. Alkhouri N, Alisi A, Okwu V, Matloob A, Ferrari F, Crudele A, De Vito R, Lopez R, Feldstein A, Nobili V. Circulating Soluble Fas and Fas Ligand Levels Are Elevated in Children with Nonalcoholic Steatohepatitis. Dig Dis Sci. 2015 Aug; 60(8):2353-9. PMID: 25764498.
        View in: PubMed
      29. Pizarro M, Solís N, Quintero P, Barrera F, Cabrera D, Rojas-de Santiago P, Arab JP, Padilla O, Roa JC, Moshage H, Wree A, Inzaugarat E, Feldstein A, Fardella CE, Baudrand R, Riquelme A, Arrese M. Beneficial effects of mineralocorticoid receptor blockade in experimental non-alcoholic steatohepatitis. Liver Int. 2015 Sep; 35(9):2129-38. PMID: 25646700.
        View in: PubMed
      30. Dechêne A, Kodde C, Kathemann S, Treckmann J, Lainka E, Paul A, Gerken G, Feldstein A, Hoyer PF, Canbay A. Endoscopic treatment of pediatric post-transplant biliary complications is safe and effective. Dig Endosc. 2015 May; 27(4):505-11. PMID: 25545826.
        View in: PubMed
      31. Arrese M, Eguchi A, Feldstein A. Circulating microRNAs: Emerging Biomarkers of Liver Disease. Semin Liver Dis. 2015 Feb; 35(1):43-54. PMID: 25632934.
        View in: PubMed
      32. Mansoor S, Yerian L, Kohli R, Xanthakos S, Angulo P, Ling S, Lopez R, Christine CK, Feldstein A, Alkhouri N. The evaluation of hepatic fibrosis scores in children with nonalcoholic Fatty liver disease. Dig Dis Sci. 2015 May; 60(5):1440-7. PMID: 25540086.
        View in: PubMed
      33. Povero D, Eguchi A, Li H, Johnson CD, Papouchado BG, Wree A, Messer K, Feldstein A. Circulating Extracellular Vesicles with Specific Proteome and Liver MicroRNAs Are Potential Biomarkers for Liver Injury in Experimental Fatty Liver Disease. PLoS One. 2014; 9(12):e113651. PMID: 25470250.
        View in: PubMed
      34. Liu H, Beier JI, Arteel GE, Ramsden CE, Feldstein A, McClain CJ, Kirpich IA. Transient receptor potential vanilloid 1 gene deficiency ameliorates hepatic injury in a mouse model of chronic binge alcohol-induced alcoholic liver disease. Am J Pathol. 2015 Jan; 185(1):43-54. PMID: 25447051.
        View in: PubMed
      35. Lazic M, Inzaugarat ME, Povero D, Zhao IC, Chen M, Nalbandian M, Miller YI, Cherñavsky AC, Feldstein A, Sears DD. Reduced Dietary Omega-6 to Omega-3 Fatty Acid Ratio and 12/15-Lipoxygenase Deficiency Are Protective against Chronic High Fat Diet-Induced Steatohepatitis. PLoS One. 2014; 9(9):e107658. PMID: 25251155.
        View in: PubMed
      36. Navarro LA, Wree A, Povero D, Berk MP, Eguchi A, Ghosh S, Papouchado BG, Erzurum SC, Feldstein A. Arginase 2 deficiency results in spontaneous steatohepatitis: A novel link between innate immune activation and hepatic de novo lipogenesis. J Hepatol. 2015 Feb; 62(2):412-20. PMID: 25234945.
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      37. Wree A, Schlattjan M, Bechmann LP, Claudel T, Sowa JP, Stojakovic T, Scharnagl H, Köfeler H, Baba HA, Gerken G, Feldstein A, Trauner M, Canbay A. Adipocyte cell size, free fatty acids and apolipoproteins are associated with non-alcoholic liver injury progression in severely obese patients. Metabolism. 2014 Dec; 63(12):1542-52. PMID: 25267016.
        View in: PubMed
      38. Eguchi A, Feldstein A. Adipocyte cell death, Fatty liver disease and associated metabolic disorders. Dig Dis. 2014; 32(5):579-85. PMID: 25034291.
        View in: PubMed
      39. Wree A, McGeough MD, Peña CA, Schlattjan M, Li H, Inzaugarat ME, Messer K, Canbay A, Hoffman HM, Feldstein A. NLRP3 inflammasome activation is required for fibrosis development in NAFLD. J Mol Med (Berl). 2014 Oct; 92(10):1069-82. PMID: 24861026.
        View in: PubMed
      40. Thapaliya S, Wree A, Povero D, Inzaugarat ME, Berk M, Dixon L, Papouchado BG, Feldstein A. Caspase 3 Inactivation Protects Against Hepatic Cell Death and Ameliorates Fibrogenesis in a Diet-Induced NASH Model. Dig Dis Sci. 2014 Jun; 59(6):1197-206. PMID: 24795036.
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      41. Newton KP, Awai HI, Feldstein A, Schwimmer JB. Letter: gender-associated cell-free microRNA profiles in non-alcoholic fatty liver disease - authors' reply. Aliment Pharmacol Ther. 2014 May; 39(9):999. PMID: 24689350.
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      42. Aytekin M, Tonelli AR, Farver CF, Feldstein A, Dweik RA. Leptin deficiency recapitulates the histological features of pulmonary arterial hypertension in mice. Int J Clin Exp Pathol. 2014; 7(5):1935-46. PMID: 24966903.
        View in: PubMed
      43. Navaneethan U, Gutierrez NG, Venkatesh PG, Jegadeesan R, Zhang R, Jang S, Sanaka MR, Vargo JJ, Parsi MA, Feldstein A, Stevens T. Lipidomic profiling of bile in distinguishing benign from malignant biliary strictures: a single-blinded pilot study. Am J Gastroenterol. 2014 Jun; 109(6):895-902. PMID: 24710507.
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      44. Lazic M, Eguchi A, Berk MP, Povero D, Papouchado B, Mulya A, Johnson CD, Feldstein A. Differential regulation of inflammation and apoptosis in Fas-resistant hepatocyte-specific Bid-deficient mice. J Hepatol. 2014 Jul; 61(1):107-15. PMID: 24681344.
        View in: PubMed
      45. Canbay A, Feldstein A, Kronenberger B, Schulze-Osthoff K, Bantel H. [Cytokeratin 18 as marker for non-invasive diagnosis and prognosis of acute and chronic liver diseases]. Z Gastroenterol. 2014 Mar; 52(3):290-5. PMID: 24622872.
        View in: PubMed
      46. Feldstein A, Patton-Ku D, Boutelle KN. Obesity, nutrition, and liver disease in children. Clin Liver Dis. 2014 Feb; 18(1):219-31. PMID: 24274876.
        View in: PubMed
      47. Wree A, Eguchi A, McGeough MD, Pena CA, Johnson CD, Canbay A, Hoffman HM, Feldstein A. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice. Hepatology. 2014 Mar; 59(3):898-910. PMID: 23813842.
        View in: PubMed
      48. Alkhouri N, Berk M, Yerian L, Lopez R, Chung YM, Zhang R, McIntyre TM, Feldstein A, Hazen SL. OxNASH Score Correlates with Histologic Features and Severity of Nonalcoholic Fatty Liver Disease. Dig Dis Sci. 2014 Jul; 59(7):1617-24. PMID: 24464211.
        View in: PubMed
      49. Eguchi A, Wree A, Feldstein A. Biomarkers of liver cell death. J Hepatol. 2014 May; 60(5):1063-74. PMID: 24412608.
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      50. Masuda T, Fu Y, Eguchi A, Czogalla J, Rose MA, Kuczkowski A, Gerasimova M, Feldstein A, Scadeng M, Vallon V. Dipeptidyl peptidase IV inhibitor lowers PPAR? agonist-induced body weight gain by affecting food intake, fat mass, and beige/brown fat but not fluid retention. Am J Physiol Endocrinol Metab. 2014 Feb; 306(4):E388-98. PMID: 24347054.
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      51. Patel NS, Peterson MR, Lin GY, Feldstein A, Schnabl B, Bettencourt R, Seki E, Sirlin CB, Loomba R. Insulin Resistance Increases MRI-Estimated Pancreatic Fat in Nonalcoholic Fatty Liver Disease and Normal Controls. Gastroenterol Res Pract. 2013; 2013:498296. PMID: 24348536.
        View in: PubMed
      52. Povero D, Eguchi A, Niesman IR, Andronikou N, de Mollerat du Jeu X, Mulya A, Berk M, Lazic M, Thapaliya S, Parola M, Patel HH, Feldstein A. Lipid-induced toxicity stimulates hepatocytes to release angiogenic microparticles that require Vanin-1 for uptake by endothelial cells. Sci Signal. 2013 Oct 8; 6(296):ra88. PMID: 24106341.
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      53. Gulati R, Radhakrishnan KR, Hupertz V, Wyllie R, Alkhouri N, Worley S, Feldstein A. Health-related quality of life in children with autoimmune liver disease. J Pediatr Gastroenterol Nutr. 2013 Oct; 57(4):444-50. PMID: 23783017.
        View in: PubMed
      54. Wree A, Broderick L, Canbay A, Hoffman HM, Feldstein A. From NAFLD to NASH to cirrhosis-new insights into disease mechanisms. Nat Rev Gastroenterol Hepatol. 2013 Nov; 10(11):627-36. PMID: 23958599.
        View in: PubMed
      55. Cusi K, Chang Z, Harrison S, Lomonaco R, Bril F, Orsak B, Ortiz-Lopez C, Hecht J, Feldstein A, Webb A, Louden C, Goros M, Tio F. Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease. J Hepatol. 2014 Jan; 60(1):167-74. PMID: 23973932.
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      56. Santoro N, Caprio S, Giannini C, Kim G, Kursawe R, Pierpont B, Shaw MM, Feldstein A. Oxidized Fatty acids: a potential pathogenic link between Fatty liver and type 2 diabetes in obese adolescents? Antioxid Redox Signal. 2014 Jan 10; 20(2):383-9. PMID: 23815500.
        View in: PubMed
      57. Santoro N, Caprio S, Feldstein A. Oxidized metabolites of linoleic acid as biomarkers of liver injury in nonalcoholic steatohepatitis. Clin Lipidol. 2013 Aug 1; 8(4):411-418. PMID: 26405460.
        View in: PubMed
      58. Bansal S, Berk M, Alkhouri N, Partrick DA, Fung JJ, Feldstein A. Stearoyl-CoA desaturase plays an important role in proliferation and chemoresistance in human hepatocellular carcinoma. J Surg Res. 2014 Jan; 186(1):29-38. PMID: 24135379.
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      59. Ramsden CE, Faurot KR, Zamora D, Suchindran CM, Macintosh BA, Gaylord S, Ringel A, Hibbeln JR, Feldstein A, Mori TA, Barden A, Lynch C, Coble R, Mas E, Palsson O, Barrow DA, Mann JD. Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial. Pain. 2013 Nov; 154(11):2441-51. PMID: 23886520.
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      60. Puri K, Nobili V, Melville K, Corte CD, Sartorelli MR, Lopez R, Feldstein A, Alkhouri N. Serum bilirubin level is inversely associated with nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr. 2013 Jul; 57(1):114-8. PMID: 23518490.
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      61. Hillian AD, McMullen MR, Sebastian BM, Roychowdhury S, Rowchowdhury S, Kashyap SR, Schauer PR, Kirwan JP, Feldstein A, Nagy LE. Mice lacking C1q are protected from high fat diet-induced hepatic insulin resistance and impaired glucose homeostasis. J Biol Chem. 2013 Aug 2; 288(31):22565-75. PMID: 23788643.
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      62. Feldstein A, Alkhouri N, De Vito R, Alisi A, Lopez R, Nobili V. Serum cytokeratin-18 fragment levels are useful biomarkers for nonalcoholic steatohepatitis in children. Am J Gastroenterol. 2013 Sep; 108(9):1526-31. PMID: 23752877.
        View in: PubMed
      63. Giannini C, Feldstein A, Santoro N, Kim G, Kursawe R, Pierpont B, Caprio S. Circulating levels of FGF-21 in obese youth: associations with liver fat content and markers of liver damage. J Clin Endocrinol Metab. 2013 Jul; 98(7):2993-3000. PMID: 23626003.
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      64. Eguchi A, Povero D, Alkhouri N, Feldstein A. Novel therapeutic targets for nonalcoholic fatty liver disease. Expert Opin Ther Targets. 2013 Jul; 17(7):773-9. PMID: 23600493.
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      65. Eguchi A, Feldstein A. Lysosomal Cathepsin D contributes to cell death during adipocyte hypertrophy. Adipocyte. 2013 Jul 1; 2(3):170-5. PMID: 23991364.
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      66. Dixon LJ, Flask CA, Papouchado BG, Feldstein A, Nagy LE. Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis. PLoS One. 2013; 8(2):e56100. PMID: 23409132.
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      67. Santoro N, Feldstein A, Enoksson E, Pierpont B, Kursawe R, Kim G, Caprio S. The association between hepatic fat content and liver injury in obese children and adolescents: effects of ethnicity, insulin resistance, and common gene variants. Diabetes Care. 2013 May; 36(5):1353-60. PMID: 23275357.
        View in: PubMed
      68. Alkhouri N, Sedki E, Alisi A, Lopez R, Pinzani M, Feldstein A, Nobili V. Combined paediatric NAFLD fibrosis index and transient elastography to predict clinically significant fibrosis in children with fatty liver disease. Liver Int. 2013 Jan; 33(1):79-85. PMID: 23146095.
        View in: PubMed
      69. Zein CO, Lopez R, Fu X, Kirwan JP, Yerian LM, McCullough AJ, Hazen SL, Feldstein A. Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: new evidence on the potential therapeutic mechanism. Hepatology. 2012 Oct; 56(4):1291-9. PMID: 22505276.
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      70. Ramsden CE, Ringel A, Feldstein A, Taha AY, MacIntosh BA, Hibbeln JR, Majchrzak-Hong SF, Faurot KR, Rapoport SI, Cheon Y, Chung YM, Berk M, Mann JD. Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans. Prostaglandins Leukot Essent Fatty Acids. 2012 Oct-Nov; 87(4-5):135-41. PMID: 22959954.
        View in: PubMed
      71. Kim G, Giannini C, Pierpont B, Feldstein A, Santoro N, Kursawe R, Shaw M, Duran E, Goldberg R, Dziura J, Caprio S. Longitudinal effects of MRI-measured hepatic steatosis on biomarkers of glucose homeostasis and hepatic apoptosis in obese youth. Diabetes Care. 2013 Jan; 36(1):130-6. PMID: 22933439.
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      72. Alkhouri N, De Vito R, Alisi A, Yerian L, Lopez R, Feldstein A, Nobili V. Development and validation of a new histological score for pediatric non-alcoholic fatty liver disease. J Hepatol. 2012 Dec; 57(6):1312-8. PMID: 22871498.
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      73. Gornicka A, Fettig J, Eguchi A, Berk MP, Thapaliya S, Dixon LJ, Feldstein A. Adipocyte hypertrophy is associated with lysosomal permeability both in vivo and in vitro: role in adipose tissue inflammation. Am J Physiol Endocrinol Metab. 2012 Sep 1; 303(5):E597-606. PMID: 22739104.
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      74. Stevens T, Berk MP, Lopez R, Chung YM, Zhang R, Parsi MA, Bronner MP, Feldstein A. Lipidomic profiling of serum and pancreatic fluid in chronic pancreatitis. Pancreas. 2012 May; 41(4):518-22. PMID: 22504378.
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      75. De Vito R, Alisi A, Masotti A, Ceccarelli S, Panera N, Citti A, Salata M, Valenti L, Feldstein A, Nobili V. Markers of activated inflammatory cells correlate with severity of liver damage in children with nonalcoholic fatty liver disease. Int J Mol Med. 2012 Jul; 30(1):49-56. PMID: 22505182.
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      76. Tonelli AR, Aytekin M, Feldstein A, Dweik RA. Leptin levels predict survival in pulmonary arterial hypertension. Pulm Circ. 2012 Apr-Jun; 2(2):214-9. PMID: 22837862.
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      77. Alkhouri N, Feldstein A. The TONIC trial: a step forward in treating pediatric nonalcoholic fatty liver disease. Hepatology. 2012 Apr; 55(4):1292-5. PMID: 22461076.
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      78. Dixon LJ, Berk M, Thapaliya S, Papouchado BG, Feldstein A. Caspase-1-mediated regulation of fibrogenesis in diet-induced steatohepatitis. Lab Invest. 2012 May; 92(5):713-23. PMID: 22411067.
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      79. Roychowdhury S, Chiang DJ, Mandal P, McMullen MR, Liu X, Cohen JI, Pollard J, Feldstein A, Nagy LE. Inhibition of apoptosis protects mice from ethanol-mediated acceleration of early markers of CCl4 -induced fibrosis but not steatosis or inflammation. Alcohol Clin Exp Res. 2012 Jul; 36(7):1139-47. PMID: 22273278.
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      80. Alisi A, Feldstein A, Villani A, Raponi M, Nobili V. Pediatric nonalcoholic fatty liver disease: a multidisciplinary approach. Nat Rev Gastroenterol Hepatol. 2012 Mar; 9(3):152-61. PMID: 22249728.
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      81. Alkhouri N, Kistangari G, Campbell C, Lopez R, Zein NN, Feldstein A. Mean platelet volume as a marker of increased cardiovascular risk in patients with nonalcoholic steatohepatitis. Hepatology. 2012 Jan; 55(1):331. PMID: 21969091.
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      82. Moses J, Alkhouri N, Shannon A, Feldstein A, Carter-Kent C. Response to hepatitis A vaccine in children with inflammatory bowel disease receiving infliximab. Inflamm Bowel Dis. 2011 Dec; 17(12):E160. PMID: 21953938.
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      83. Alkhouri N, Morris-Stiff G, Campbell C, Lopez R, Tamimi TA, Yerian L, Zein NN, Feldstein A. Neutrophil to lymphocyte ratio: a new marker for predicting steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease. Liver Int. 2012 Feb; 32(2):297-302. PMID: 22097893.
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      84. Moses J, Alkhouri N, Shannon A, Raig K, Lopez R, Danziger-Isakov L, Feldstein A, Zein NN, Wyllie R, Carter-Kent C. Hepatitis B immunity and response to booster vaccination in children with inflammatory bowel disease treated with infliximab. Am J Gastroenterol. 2012 Jan; 107(1):133-8. PMID: 21876562.
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      85. Zein CO, Yerian LM, Gogate P, Lopez R, Kirwan JP, Feldstein A, McCullough AJ. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology. 2011 Nov; 54(5):1610-9. PMID: 21748765.
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      86. Sebastian BM, Roychowdhury S, Tang H, Hillian AD, Feldstein A, Stahl GL, Takahashi K, Nagy LE. Identification of a cytochrome P4502E1/Bid/C1q-dependent axis mediating inflammation in adipose tissue after chronic ethanol feeding to mice. J Biol Chem. 2011 Oct 14; 286(41):35989-97. PMID: 21856753.
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      87. Nobili V, Della Corte C, Monti L, Alisi A, Feldstein A. The use of ultrasound in clinical setting for children affected by NAFLD: is it safe and accurate? Ital J Pediatr. 2011; 37:36. PMID: 21810223.
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      88. Shannon A, Alkhouri N, Carter-Kent C, Monti L, Devito R, Lopez R, Feldstein A, Nobili V. Ultrasonographic quantitative estimation of hepatic steatosis in children With NAFLD. J Pediatr Gastroenterol Nutr. 2011 Aug; 53(2):190-5. PMID: 21788761.
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      89. Nobili V, Carter-Kent C, Feldstein A. The role of lifestyle changes in the management of chronic liver disease. BMC Med. 2011; 9:70. PMID: 21645344.
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      90. Alkhouri N, Carter-Kent C, Elias M, Feldstein A. Atherogenic dyslipidemia and cardiovascular risk in children with nonalcoholic fatty liver disease. Clin Lipidol. 2011 Jun 1; 6(3):305-314. PMID: 22162978.
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      91. Feldstein A, Bailey SM. Emerging role of redox dysregulation in alcoholic and nonalcoholic fatty liver disease. Antioxid Redox Signal. 2011 Jul 15; 15(2):421-4. PMID: 21254858.
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      92. Kohli R, Feldstein A. NASH animal models: are we there yet? J Hepatol. 2011 Oct; 55(4):941-3. PMID: 21708199.
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      93. Gornicka A, Morris-Stiff G, Thapaliya S, Papouchado BG, Berk M, Feldstein A. Transcriptional profile of genes involved in oxidative stress and antioxidant defense in a dietary murine model of steatohepatitis. Antioxid Redox Signal. 2011 Jul 15; 15(2):437-45. PMID: 21194384.
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      94. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein A, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7; 472(7341):57-63. PMID: 21475195.
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      95. Alkhouri N, Carter-Kent C, Feldstein A. Apoptosis in nonalcoholic fatty liver disease: diagnostic and therapeutic implications. Expert Rev Gastroenterol Hepatol. 2011 Apr; 5(2):201-12. PMID: 21476915.
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      96. Tamimi TI, Elgouhari HM, Alkhouri N, Yerian LM, Berk MP, Lopez R, Schauer PR, Zein NN, Feldstein A. An apoptosis panel for nonalcoholic steatohepatitis diagnosis. J Hepatol. 2011 Jun; 54(6):1224-9. PMID: 21145805.
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      97. Adams LA, Feldstein A. Non-invasive diagnosis of nonalcoholic fatty liver and nonalcoholic steatohepatitis. J Dig Dis. 2011 Feb; 12(1):10-6. PMID: 21091933.
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      98. Carter-Kent C, Brunt EM, Yerian LM, Alkhouri N, Angulo P, Kohli R, Ling SC, Xanthakos SA, Whitington PF, Charatcharoenwitthaya P, Yap J, Lopez R, McCullough AJ, Feldstein A. Relations of steatosis type, grade, and zonality to histological features in pediatric nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2011 Feb; 52(2):190-7. PMID: 21240012.
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      99. Hanouneh IA, Macaron C, Lopez R, Feldstein A, Yerian L, Eghtesad B, Zein NN. Recurrence of Disease Following Liver Transplantation: Nonalcoholic Steatohepatitis vs Hepatitis C Virus Infection. Int J Organ Transplant Med. 2011; 2(2):57-65. PMID: 25013596.
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      100. Feldstein A. Novel insights into the pathophysiology of nonalcoholic fatty liver disease. Semin Liver Dis. 2010 Nov; 30(4):391-401. PMID: 20960378.
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      101. Alkhouri N, Carter-Kent C, Lopez R, Rosenberg WM, Pinzani M, Bedogni G, Feldstein A, Nobili V. A combination of the pediatric NAFLD fibrosis index and enhanced liver fibrosis test identifies children with fibrosis. Clin Gastroenterol Hepatol. 2011 Feb; 9(2):150-5. PMID: 20888433.
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      102. Adams LA, Feldstein A. Nonalcoholic steatohepatitis: risk factors and diagnosis. Expert Rev Gastroenterol Hepatol. 2010 Oct; 4(5):623-35. PMID: 20932147.
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      103. Feldstein A, Nobili V. Biomarkers in nonalcoholic fatty liver disease: a new era in diagnosis and staging of disease in children. J Pediatr Gastroenterol Nutr. 2010 Oct; 51(4):378-9. PMID: 20808243.
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      104. Kohli R, Kirby M, Xanthakos SA, Softic S, Feldstein A, Saxena V, Tang PH, Miles L, Miles MV, Balistreri WF, Woods SC, Seeley RJ. High-fructose, medium chain trans fat diet induces liver fibrosis and elevates plasma coenzyme Q9 in a novel murine model of obesity and nonalcoholic steatohepatitis. Hepatology. 2010 Sep; 52(3):934-44. PMID: 20607689.
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      105. Morris-Stiff G, Feldstein A. Fibroblast growth factor 21 as a biomarker for NAFLD: integrating pathobiology into clinical practice. J Hepatol. 2010 Nov; 53(5):795-6. PMID: 20800308.
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      106. Feldstein A, Lopez R, Tamimi TA, Yerian L, Chung YM, Berk M, Zhang R, McIntyre TM, Hazen SL. Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Lipid Res. 2010 Oct; 51(10):3046-54. PMID: 20631297.
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      107. Nobili V, Alkhouri N, Bartuli A, Manco M, Lopez R, Alisi A, Feldstein A. Severity of liver injury and atherogenic lipid profile in children with nonalcoholic fatty liver disease. Pediatr Res. 2010 Jun; 67(6):665-70. PMID: 20496475.
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      108. Yang L, Latchoumycandane C, McMullen MR, Pratt BT, Zhang R, Papouchado BG, Nagy LE, Feldstein A, McIntyre TM. Chronic alcohol exposure increases circulating bioactive oxidized phospholipids. J Biol Chem. 2010 Jul 16; 285(29):22211-20. PMID: 20460374.
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      109. Radhakrishnan KR, Alkhouri N, Worley S, Arrigain S, Hupertz V, Kay M, Yerian L, Wyllie R, Feldstein A. Autoimmune hepatitis in children--impact of cirrhosis at presentation on natural history and long-term outcome. Dig Liver Dis. 2010 Oct; 42(10):724-8. PMID: 20163994.
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      110. Alkhouri N, Tamimi TA, Yerian L, Lopez R, Zein NN, Feldstein A. The inflamed liver and atherosclerosis: a link between histologic severity of nonalcoholic fatty liver disease and increased cardiovascular risk. Dig Dis Sci. 2010 Sep; 55(9):2644-50. PMID: 19960252.
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      111. Elgouhari HM, Zein CO, Hanouneh I, Feldstein A, Zein NN. Diabetes mellitus is associated with impaired response to antiviral therapy in chronic hepatitis C infection. Dig Dis Sci. 2009 Dec; 54(12):2699-705. PMID: 19148751.
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      112. Alkhouri N, Gornicka A, Berk MP, Thapaliya S, Dixon LJ, Kashyap S, Schauer PR, Feldstein A. Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J Biol Chem. 2010 Jan 29; 285(5):3428-38. PMID: 19940134.
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      113. Alkhouri N, Lopez R, Berk M, Feldstein A. Serum retinol-binding protein 4 levels in patients with nonalcoholic fatty liver disease. J Clin Gastroenterol. 2009 Nov-Dec; 43(10):985-9. PMID: 19525859.
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      114. Carter-Kent C, Yerian LM, Brunt EM, Angulo P, Kohli R, Ling SC, Xanthakos SA, Whitington PF, Charatcharoenwitthaya P, Yap J, Lopez R, McCullough AJ, Feldstein A. Nonalcoholic steatohepatitis in children: a multicenter clinicopathological study. Hepatology. 2009 Oct; 50(4):1113-20. PMID: 19637190.
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      115. Feldstein A, Wieckowska A, Lopez AR, Liu YC, Zein NN, McCullough AJ. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology. 2009 Oct; 50(4):1072-8. PMID: 19585618.
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      116. Chen R, Feldstein A, McIntyre TM. Suppression of mitochondrial function by oxidatively truncated phospholipids is reversible, aided by bid, and suppressed by Bcl-XL. J Biol Chem. 2009 Sep 25; 284(39):26297-308. PMID: 19654426.
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      117. Alkhouri N, Dixon LJ, Feldstein A. Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal. Expert Rev Gastroenterol Hepatol. 2009 Aug; 3(4):445-51. PMID: 19673631.
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      118. Carter-Kent C, Feldstein A. Non-alcoholic steatohepatitis over multiple generations. Dig Dis Sci. 2010 May; 55(5):1494-7. PMID: 19629685.
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      119. Feldstein A, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut. 2009 Nov; 58(11):1538-44. PMID: 19625277.
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      120. Kashyap SR, Diab DL, Baker AR, Yerian L, Bajaj H, Gray-McGuire C, Schauer PR, Gupta M, Feldstein A, Hazen SL, Stein CM. Triglyceride levels and not adipokine concentrations are closely related to severity of nonalcoholic fatty liver disease in an obesity surgery cohort. Obesity (Silver Spring). 2009 Sep; 17(9):1696-701. PMID: 19360015.
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      121. Feldstein A, Kleiner D, Kravetz D, Buck M. Severe hepatocellular injury with apoptosis induced by a hepatitis C polymerase inhibitor. J Clin Gastroenterol. 2009 Apr; 43(4):374-81. PMID: 19098685.
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      122. Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein A. Role of interleukin-6 in human nonalcoholic steatohepatitis. Response to Dogru et al. Am J Gastroenterol. 2009 Mar; 104(3):author reply 788. PMID: 19174778.
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      123. Nobili V, Alkhouri N, Alisi A, Ottino S, Lopez R, Manco M, Feldstein A. Retinol-binding protein 4: a promising circulating marker of liver damage in pediatric nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009 May; 7(5):575-9. PMID: 19268270.
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      124. Li ZZ, Berk M, McIntyre TM, Feldstein A. Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase. J Biol Chem. 2009 Feb 27; 284(9):5637-44. PMID: 19119140.
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      125. Wieckowska A, Feldstein A. Diagnosis of nonalcoholic fatty liver disease: invasive versus noninvasive. Semin Liver Dis. 2008 Nov; 28(4):386-95. PMID: 18956295.
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      126. Hanouneh IA, Feldstein A, McCullough AJ, Miller C, Aucejo F, Yerian L, Lopez R, Zein NN. The significance of metabolic syndrome in the setting of recurrent hepatitis C after liver transplantation. Liver Transpl. 2008 Sep; 14(9):1287-93. PMID: 18756451.
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      127. Diab DL, Yerian L, Schauer P, Kashyap SR, Lopez R, Hazen SL, Feldstein A. Cytokeratin 18 fragment levels as a noninvasive biomarker for nonalcoholic steatohepatitis in bariatric surgery patients. Clin Gastroenterol Hepatol. 2008 Nov; 6(11):1249-54. PMID: 18995215.
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      128. Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein A. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol. 2008 Jun; 103(6):1372-9. PMID: 18510618.
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      129. Li Z, Berk M, McIntyre TM, Gores GJ, Feldstein A. The lysosomal-mitochondrial axis in free fatty acid-induced hepatic lipotoxicity. Hepatology. 2008 May; 47(5):1495-503. PMID: 18220271.
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      130. Hanouneh IA, Feldstein A, Lopez R, Yerian L, Pillai A, Zein CO, Zein NN. Clinical significance of metabolic syndrome in the setting of chronic hepatitis C virus infection. Clin Gastroenterol Hepatol. 2008 May; 6(5):584-9. PMID: 18455698.
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      131. Carter-Kent C, Zein NN, Feldstein A. Cytokines in the pathogenesis of fatty liver and disease progression to steatohepatitis: implications for treatment. Am J Gastroenterol. 2008 Apr; 103(4):1036-42. PMID: 18177455.
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      132. Carter-Kent C, Radhakrishnan K, Feldstein A. Increasing calories, decreasing morbidity and mortality: is improved nutrition the answer to better outcomes in patients with biliary atresia? Hepatology. 2007 Nov; 46(5):1329-31. PMID: 17969044.
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      133. Wieckowska A, McCullough AJ, Feldstein A. Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology. 2007 Aug; 46(2):582-9. PMID: 17661414.
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      134. Wieckowska A, Zein NN, Yerian LM, Lopez AR, McCullough AJ, Feldstein A. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology. 2006 Jul; 44(1):27-33. PMID: 16799979.
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      135. Feldstein A, Werneburg NW, Li Z, Bronk SF, Gores GJ. Bax inhibition protects against free fatty acid-induced lysosomal permeabilization. Am J Physiol Gastrointest Liver Physiol. 2006 Jun; 290(6):G1339-46. PMID: 16484678.
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      136. Wieckowska A, Feldstein A. Nonalcoholic fatty liver disease in the pediatric population: a review. Curr Opin Pediatr. 2005 Oct; 17(5):636-41. PMID: 16160540.
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      137. Feldstein A, Gores GJ. Apoptosis in alcoholic and nonalcoholic steatohepatitis. Front Biosci. 2005; 10:3093-9. PMID: 15970563.
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      138. Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005 Jul; 129(1):113-21. PMID: 16012941.
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      139. Feldstein A, Papouchado BG, Angulo P, Sanderson S, Adams L, Gores GJ. Hepatic stellate cells and fibrosis progression in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2005 Apr; 3(4):384-9. PMID: 15822044.
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      140. Feldstein A, Gores GJ. An apoptosis biomarker goes to the HCV clinic. Hepatology. 2004 Nov; 40(5):1044-6. PMID: 15486920.
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      141. Feldstein A, Gores GJ. Steatohepatitis and apoptosis: therapeutic implications. Am J Gastroenterol. 2004 Sep; 99(9):1718-9. PMID: 15330908.
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      142. Feldstein A, Werneburg NW, Canbay A, Guicciardi ME, Bronk SF, Rydzewski R, Burgart LJ, Gores GJ. Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway. Hepatology. 2004 Jul; 40(1):185-94. PMID: 15239102.
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      143. Adams LA, Feldstein A, Lindor KD, Angulo P. Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction. Hepatology. 2004 Apr; 39(4):909-14. PMID: 15057893.
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      144. Feldstein A, Canbay A, Guicciardi ME, Higuchi H, Bronk SF, Gores GJ. Diet associated hepatic steatosis sensitizes to Fas mediated liver injury in mice. J Hepatol. 2003 Dec; 39(6):978-83. PMID: 14642615.
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      145. Canbay A, Feldstein A, Baskin-Bey E, Bronk SF, Gores GJ. The caspase inhibitor IDN-6556 attenuates hepatic injury and fibrosis in the bile duct ligated mouse. J Pharmacol Exp Ther. 2004 Mar; 308(3):1191-6. PMID: 14617689.
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      146. Canbay A, Feldstein A, Higuchi H, Werneburg N, Grambihler A, Bronk SF, Gores GJ. Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression. Hepatology. 2003 Nov; 38(5):1188-98. PMID: 14578857.
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      147. Feldstein A, Canbay A, Angulo P, Taniai M, Burgart LJ, Lindor KD, Gores GJ. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology. 2003 Aug; 125(2):437-43. PMID: 12891546.
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      148. Feldstein A, Perrault J, El-Youssif M, Lindor KD, Freese DK, Angulo P. Primary sclerosing cholangitis in children: a long-term follow-up study. Hepatology. 2003 Jul; 38(1):210-7. PMID: 12830004.
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      149. Canbay A, Guicciardi ME, Higuchi H, Feldstein A, Bronk SF, Rydzewski R, Taniai M, Gores GJ. Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis. J Clin Invest. 2003 Jul; 112(2):152-9. PMID: 12865404.
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      150. Wilson SH, Chade AR, Feldstein A, Sawamura T, Napoli C, Lerman A, Lerman LO. Lipid-lowering-independent effects of simvastatin on the kidney in experimental hypercholesterolaemia. Nephrol Dial Transplant. 2003 Apr; 18(4):703-9. PMID: 12637638.
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      151. Feldstein A, Razonable RR, Boyce TG, Freese DK, El-Youssef M, Perrault J, Paya CV, Ishitani MB. Prevalence and clinical significance of human herpesviruses 6 and 7 active infection in pediatric liver transplant patients. Pediatr Transplant. 2003 Apr; 7(2):125-9. PMID: 12654053.
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      152. Feldstein A, Miller SM, El-Youssef M, Rodeberg D, Lindor NM, Burgart LJ, Szurszewski JH, Farrugia G. Chronic intestinal pseudoobstruction associated with altered interstitial cells of cajal networks. J Pediatr Gastroenterol Nutr. 2003 Apr; 36(4):492-7. PMID: 12658043.
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      153. Feldstein A, Krier JD, Sarafov MH, Lerman A, Best PJ, Wilson SH, Lerman LO. In vivo renal vascular and tubular function in experimental hypercholesterolemia. Hypertension. 1999 Oct; 34(4 Pt 2):859-64. PMID: 10523374.
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      154. Romero JC, Feldstein A, Rodriguez-Porcel MG, Cases-Amenos A. New insights into the pathophysiology of renovascular hypertension. Mayo Clin Proc. 1997 Mar; 72(3):251-60. PMID: 9070202.
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