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Haptoglobin 2 Allele is Associated With Histologic Response to Vitamin E in Subjects With Nonalcoholic Steatohepatitis.

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  • Additional Information
    • Corporate Authors:
    • Source:
      Publisher: Wolters Kluwer Health, Inc Country of Publication: United States NLM ID: 7910017 Publication Model: Print Cited Medium: Internet ISSN: 1539-2031 (Electronic) Linking ISSN: 01920790 NLM ISO Abbreviation: J Clin Gastroenterol Subsets: MEDLINE
    • Publication Information:
      Publication: <2015- > : Philadelphia, PA : Wolters Kluwer Health, Inc.
      Original Publication: New York, Masson.
    • Subject Terms:
    • 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.
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    • Grant Information:
      R03 DK081450 United States DK NIDDK NIH HHS; U01 DK061731 United States DK NIDDK NIH HHS; UL1 TR000006 United States TR NCATS NIH HHS; R01 DK105961 United States DK NIDDK NIH HHS; UL1 TR000058 United States TR NCATS NIH HHS; UL1 TR000436 United States TR NCATS NIH HHS; UL1 TR001422 United States TR NCATS NIH HHS; T32 DK007150 United States DK NIDDK NIH HHS; U01 DK061728 United States DK NIDDK NIH HHS; UL1 TR000439 United States TR NCATS NIH HHS; UL1 TR000454 United States TR NCATS NIH HHS; TL1 TR001107 United States TR NCATS NIH HHS; UL1 TR000004 United States TR NCATS NIH HHS; UL1 TR002345 United States TR NCATS NIH HHS; R01 DK081410 United States DK NIDDK NIH HHS; U01 DK061737 United States DK NIDDK NIH HHS; U01 DK061713 United States DK NIDDK NIH HHS; U01 DK061732 United States DK NIDDK NIH HHS; UL1 TR000150 United States TR NCATS NIH HHS; UL1 TR002548 United States TR NCATS NIH HHS; U01 DK061718 United States DK NIDDK NIH HHS; UL1 TR001442 United States TR NCATS NIH HHS; U01 DK061730 United States DK NIDDK NIH HHS; U24 DK061730 United States DK NIDDK NIH HHS; U01 DK061738 United States DK NIDDK NIH HHS; UL1 TR000424 United States TR NCATS NIH HHS; UL1 TR002378 United States TR NCATS NIH HHS; UL1 TR000448 United States TR NCATS NIH HHS; U01 DK061734 United States DK NIDDK NIH HHS; UL1 TR001425 United States TR NCATS NIH HHS; UL1 TR002319 United States TR NCATS NIH HHS; UL1 TR000040 United States TR NCATS NIH HHS; UL1 TR000077 United States TR NCATS NIH HHS; UL1 TR000423 United States TR NCATS NIH HHS; UL1 TR000100 United States TR NCATS NIH HHS
    • Accession Number:
      0 (Haptoglobins)
      1406-18-4 (Vitamin E)
    • Publication Date:
      Date Created: 20181227 Date Completed: 20200929 Latest Revision: 20201101
    • Publication Date:
      20220902
    • Accession Number:
      PMC6588507
    • Accession Number:
      10.1097/MCG.0000000000001142
    • Accession Number:
      30586008