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

for the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)

Research output: Contribution to journalArticle

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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 ?- 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.

Original languageEnglish (US)
JournalJournal of Clinical Gastroenterology
DOIs
StateAccepted/In press - Jan 1 2018

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Haptoglobins
Vitamin E
Alleles
Genotype
Placebos
Liver
Fatty Liver
Enzymes
Regression Analysis
Non-alcoholic Fatty Liver Disease
gamma-Glutamyltransferase
Aspartate Aminotransferases
Alanine Transaminase
Alkaline Phosphatase
Histology
Diabetes Mellitus
Oxidative Stress
Fibrosis
Therapeutics
Biomarkers

Keywords

  • haptoglobin genotype
  • nonalcoholic fatty liver disease
  • nonalcoholic steatohepatitis
  • oxidative stress
  • vitamin E

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Haptoglobin 2 Allele is Associated With Histologic Response to Vitamin E in Subjects With Nonalcoholic Steatohepatitis. / for the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN).

In: Journal of Clinical Gastroenterology, 01.01.2018.

Research output: Contribution to journalArticle

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title = "Haptoglobin 2 Allele is Associated With Histologic Response to Vitamin E in Subjects With Nonalcoholic Steatohepatitis",
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 ?- 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.",
keywords = "haptoglobin genotype, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, oxidative stress, vitamin E",
author = "{for the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)} and Banini, {Bubu A.} and Cazanave, {Sophie C.} and Yates, {Katherine P.} and Amon Asgharpour and Robert Vincent and Faridoddin Mirshahi and Peter Le and Contos, {Melissa J.} and James Tonascia and Naga Chalasani and Kowdley, {Kris V.} and Mccullough, {Arthur J.} and Behling, {Cynthia A.} and Schwimmer, {Jeffrey B.} and Lavine, {Joel E.} and Sanyal, {Arun J.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1097/MCG.0000000000001142",
language = "English (US)",
journal = "Journal of Clinical Gastroenterology",
issn = "0192-0790",
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T1 - Haptoglobin 2 Allele is Associated With Histologic Response to Vitamin E in Subjects With Nonalcoholic Steatohepatitis

AU - for the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)

AU - Banini, Bubu A.

AU - Cazanave, Sophie C.

AU - Yates, Katherine P.

AU - Asgharpour, Amon

AU - Vincent, Robert

AU - Mirshahi, Faridoddin

AU - Le, Peter

AU - Contos, Melissa J.

AU - Tonascia, James

AU - Chalasani, Naga

AU - Kowdley, Kris V.

AU - Mccullough, Arthur J.

AU - Behling, Cynthia A.

AU - Schwimmer, Jeffrey B.

AU - Lavine, Joel E.

AU - Sanyal, Arun J.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 ?- 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.

AB - 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 ?- 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.

KW - haptoglobin genotype

KW - nonalcoholic fatty liver disease

KW - nonalcoholic steatohepatitis

KW - oxidative stress

KW - vitamin E

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