Haptoglobin 2 allele is associated with histological response to vitamin E in subjects with nonalcoholic steatohepatitis
| Autor: | Bubu A. Banini, Robert Vincent, Amon Asgharpour, Katherine P. Yates, Kris V. Kowdley, James Tonascia, Melissa J. Contos, Cynthia Behling, Peter Le, Arthur J. McCullough, Faridoddin Mirshahi, Sophie C. Cazanave, Arun J. Sanyal, Joel E. Lavine, Jeffrey B. Schwimmer, Naga Chalasani |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Genotype medicine.medical_treatment Placebo Gastroenterology Article 03 medical and health sciences 0302 clinical medicine Non-alcoholic Fatty Liver Disease Diabetes mellitus Internal medicine Nonalcoholic fatty liver disease medicine Humans Vitamin E Alleles Randomized Controlled Trials as Topic biology Haptoglobins business.industry Haptoglobin medicine.disease Treatment Outcome 030220 oncology & carcinogenesis biology.protein Alkaline phosphatase 030211 gastroenterology & hepatology Female Steatohepatitis business |
| Zdroj: | J Clin Gastroenterol |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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