Bubu A Banini1, Sophie C Cazanave1,2, Katherine P Yates3, Amon Asgharpour1,4, Robert Vincent1,5, Faridoddin Mirshahi1, Peter Le1, Melissa J Contos6, James Tonascia3, Naga P Chalasani7, Kris V Kowdley8, Arthur J McCullough9, Cynthia A Behling10, Jeffrey B Schwimmer11,12, Joel E Lavine13, Arun J Sanyal1. 1. Division of Gastroenterology, Department of Internal Medicine. 2. Glympse Bio, Cambridge, MA. 3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 4. Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sanai. 5. Indiana Gastroenterology and Hepatology. 6. Division of Surgical Pathology, Department of Pathology, VCU School of Medicine, Richmond, VA. 7. Division of Gastroenterology and Hepatology, Indiana Fatty Liver Disease Research Group, Indiana University School of Medicine, Indianapolis, IN. 8. Liver Care Network, Swedish Medical Center, Seattle, WA. 9. Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH. 10. Department of Pathology, Sharp Health System. 11. Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, CA. 12. Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego. 13. Department of Pediatrics, Columbia University, New York, NY.
Abstract
BACKGROUND: Haptoglobin (Hp) genotype has been linked to oxidative stress and cardiovascular outcomes in response to vitamin E (VitE) among patients with diabetes mellitus. Its effect on histologic response to VitE in nonalcoholic steatohepatitis (NASH) is unknown. GOALS: Our objective was to determine if Hp genotype associates with response to VitE in patients with NASH. STUDY: A post hoc analysis of 228 patients receiving VitE or placebo in 2 clinical trials was performed. Regression analysis was used to assess the effect of VitE versus placebo, by Hp genotype (1-1, 2-1, or 2-2), on histologic features and laboratory markers of nonalcoholic fatty liver disease, comparing baseline to end of treatment values. An interaction term was included in the regression models to assess differential treatment effect across Hp genotype. RESULTS: Hp 2-2 patients treated with VitE versus placebo showed significant histologic improvement (51% vs. 20%; OR=4.2; P=0.006), resolution of steatohepatitis (44% vs. 12%; OR=6.2; P=0.009), decrease in nonalcoholic fatty liver disease Activity Score (NAS) (-2.2 vs. -0.6; P=0.001), and decrease in liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase. Hp 2-1 patients on VitE versus placebo showed improved resolution of steatohepatitis, NAS and liver enzymes. Hp 1-1 patients showed no significant improvement in histology or liver enzymes. VitE had no effect on fibrosis stage in any group. Regression analysis showed incremental benefit of having Hp 2-2 or 2-1 versus 1-1 for all liver enzyme. CONCLUSIONS: Hp 2 allele is associated with greater histologic and biological improvement in NASH with VitE treatment compared with the Hp 1 allele.
BACKGROUND:Haptoglobin (Hp) genotype has been linked to oxidative stress and cardiovascular outcomes in response to vitamin E (VitE) among patients with diabetes mellitus. Its effect on histologic response to VitE in nonalcoholic steatohepatitis (NASH) is unknown. GOALS: Our objective was to determine if Hp genotype associates with response to VitE in patients with NASH. STUDY: A post hoc analysis of 228 patients receiving VitE or placebo in 2 clinical trials was performed. Regression analysis was used to assess the effect of VitE versus placebo, by Hp genotype (1-1, 2-1, or 2-2), on histologic features and laboratory markers of nonalcoholic fatty liver disease, comparing baseline to end of treatment values. An interaction term was included in the regression models to assess differential treatment effect across Hp genotype. RESULTS: Hp 2-2 patients treated with VitE versus placebo showed significant histologic improvement (51% vs. 20%; OR=4.2; P=0.006), resolution of steatohepatitis (44% vs. 12%; OR=6.2; P=0.009), decrease in nonalcoholic fatty liver disease Activity Score (NAS) (-2.2 vs. -0.6; P=0.001), and decrease in liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase. Hp 2-1 patients on VitE versus placebo showed improved resolution of steatohepatitis, NAS and liver enzymes. Hp 1-1patients showed no significant improvement in histology or liver enzymes. VitE had no effect on fibrosis stage in any group. Regression analysis showed incremental benefit of having Hp 2-2 or 2-1 versus 1-1 for all liver enzyme. CONCLUSIONS: Hp 2 allele is associated with greater histologic and biological improvement in NASH with VitE treatment compared with the Hp 1 allele.
Authors: David E Kleiner; Elizabeth M Brunt; Mark Van Natta; Cynthia Behling; Melissa J Contos; Oscar W Cummings; Linda D Ferrell; Yao-Chang Liu; Michael S Torbenson; Aynur Unalp-Arida; Matthew Yeh; Arthur J McCullough; Arun J Sanyal Journal: Hepatology Date: 2005-06 Impact factor: 17.425
Authors: Werner Koch; Wolfgang Latz; Marianne Eichinger; Ariel Roguin; Andrew P Levy; Albert Schömig; Adnan Kastrati Journal: Clin Chem Date: 2002-09 Impact factor: 8.327
Authors: Timothy J Key; Paul N Appleby; Ruth C Travis; Demetrius Albanes; Anthony J Alberg; Aurelio Barricarte; Amanda Black; Heiner Boeing; H Bas Bueno-de-Mesquita; June M Chan; Chu Chen; Michael B Cook; Jenny L Donovan; Pilar Galan; Rebecca Gilbert; Graham G Giles; Edward Giovannucci; Gary E Goodman; Phyllis J Goodman; Marc J Gunter; Freddie C Hamdy; Markku Heliövaara; Kathy J Helzlsouer; Brian E Henderson; Serge Hercberg; Judy Hoffman-Bolton; Robert N Hoover; Mattias Johansson; Kay-Tee Khaw; Irena B King; Paul Knekt; Laurence N Kolonel; Loic Le Marchand; Satu Männistö; Richard M Martin; Haakon E Meyer; Alison M Mondul; Kristin A Moy; David E Neal; Marian L Neuhouser; Domenico Palli; Elizabeth A Platz; Camille Pouchieu; Harri Rissanen; Jeannette M Schenk; Gianluca Severi; Meir J Stampfer; Anne Tjønneland; Mathilde Touvier; Antonia Trichopoulou; Stephanie J Weinstein; Regina G Ziegler; Cindy Ke Zhou; Naomi E Allen Journal: Am J Clin Nutr Date: 2015-10-07 Impact factor: 7.045
Authors: Margery A Connelly; Jonathan Velez Rivera; John R Guyton; Mohammad Shadab Siddiqui; Arun J Sanyal Journal: Aliment Pharmacol Ther Date: 2020-07-08 Impact factor: 9.524