Relationship between resolution of non-alcoholic steatohepatitis and changes in lipoprotein sub-fractions: a post-hoc analysis of the PIVENS trial

the NASH Clinical Research Network

Research output: Contribution to journalArticle

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Abstract

Background: Dyslipidaemia is frequent in non-alcoholic steatohepatitis (NASH); however, it is unclear if improvement in liver histology is associated with favourable changes in cardiovascular disease (CVD) risk. Aims: To evaluate the relationship of NASH resolution and lipoprotein subfraction levels, markers of endothelial dysfunction, and macrophage activation. Methods: One hundred and seventeen individuals with NASH who participated in the Pioglitazone vs Vitamin E vs Placebo for the Treatment of Nondiabetic Patients with NASH (PIVENS) trial with paired liver biopsies and serum samples available at baseline and after 96 weeks of treatment were included. Participants in the PIVENS trials received vitamin E, pioglitazone, or placebo for 96 weeks. Lipoprotein subfraction levels, intracellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), E-selectin, and sCD163 levels were assessed at baseline and week 96 and their relationship with NASH resolution was examined. Results: Fifty-seven individuals had NASH resolution and 60 individuals did not have resolution of NASH. NASH resolution was associated with favourable changes in lipoprotein subfraction levels compared to those without NASH resolution. Individuals with resolution of NASH had a significantly increased mean peak LDL diameter (ratio of geometric means [96 weeks vs baseline] 1.007 vs 0.996, P = 0.004), and higher frequency of LDL phenotype A (58% vs 33%, P = 0.003) at week 96, after adjustment for relevant co-variates including treatment group. No differences in VCAM, ICAM, E-selectin, or sCD163 levels by NASH resolution were found. Conclusions: NASH resolution is associated with favourable changes in a subset of serum lipoprotein levels. More studies are warranted to understand if these favourable changes are associated with decreased risk of CVD.

Original languageEnglish (US)
Pages (from-to)1205-1213
Number of pages9
JournalAlimentary Pharmacology and Therapeutics
Volume49
Issue number9
DOIs
StatePublished - May 1 2019

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Fatty Liver
Lipoproteins
pioglitazone
E-Selectin
Vitamin E
Cardiovascular Diseases
Placebos
Macrophage Activation
Liver
Dyslipidemias
Serum
Blood Vessels
Histology
Therapeutics
Phenotype
Biopsy

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

Cite this

Relationship between resolution of non-alcoholic steatohepatitis and changes in lipoprotein sub-fractions : a post-hoc analysis of the PIVENS trial. / the NASH Clinical Research Network.

In: Alimentary Pharmacology and Therapeutics, Vol. 49, No. 9, 01.05.2019, p. 1205-1213.

Research output: Contribution to journalArticle

@article{af49ab36410f4d8090f62b72780517ad,
title = "Relationship between resolution of non-alcoholic steatohepatitis and changes in lipoprotein sub-fractions: a post-hoc analysis of the PIVENS trial",
abstract = "Background: Dyslipidaemia is frequent in non-alcoholic steatohepatitis (NASH); however, it is unclear if improvement in liver histology is associated with favourable changes in cardiovascular disease (CVD) risk. Aims: To evaluate the relationship of NASH resolution and lipoprotein subfraction levels, markers of endothelial dysfunction, and macrophage activation. Methods: One hundred and seventeen individuals with NASH who participated in the Pioglitazone vs Vitamin E vs Placebo for the Treatment of Nondiabetic Patients with NASH (PIVENS) trial with paired liver biopsies and serum samples available at baseline and after 96 weeks of treatment were included. Participants in the PIVENS trials received vitamin E, pioglitazone, or placebo for 96 weeks. Lipoprotein subfraction levels, intracellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), E-selectin, and sCD163 levels were assessed at baseline and week 96 and their relationship with NASH resolution was examined. Results: Fifty-seven individuals had NASH resolution and 60 individuals did not have resolution of NASH. NASH resolution was associated with favourable changes in lipoprotein subfraction levels compared to those without NASH resolution. Individuals with resolution of NASH had a significantly increased mean peak LDL diameter (ratio of geometric means [96 weeks vs baseline] 1.007 vs 0.996, P = 0.004), and higher frequency of LDL phenotype A (58{\%} vs 33{\%}, P = 0.003) at week 96, after adjustment for relevant co-variates including treatment group. No differences in VCAM, ICAM, E-selectin, or sCD163 levels by NASH resolution were found. Conclusions: NASH resolution is associated with favourable changes in a subset of serum lipoprotein levels. More studies are warranted to understand if these favourable changes are associated with decreased risk of CVD.",
author = "{the NASH Clinical Research Network} and Corey, {Kathleen E.} and Wilson, {Laura A.} and Akif Altinbas and Yates, {Katherine P.} and Kleiner, {David E.} and Chung, {Raymond T.} and Krauss, {Ronald M.} and Naga Chalasani and Diane Bringman and Srinivasan Dasarathy and Ariel Feldstein and Carol Hawkins and Liu, {Yao Chang} and Arthur McCullough and Ruth Sargent and Margaret Stager and Manal Abdelmalek and Diehl, {Anna Mae} and Marcia Gottfried and Cynthia Guy and Paul Killenberg and Samantha Kwan and Pan, {Yi Ping} and Dawn Piercy and Melissa Smith and Kimberly Pfeifer and Scheimann, {Ann O.} and Michael Torbenson and Prajakta Bhimalli and Elizabeth Byam and Oscar Cummings and Ann Klipsch and Lydia Lee and Jean Molleston and Linda Ragozzino and Girish Subbarao and Raj Vuppalanchi and Sarah Barlow and Brunt, {Elizabeth M.} and Jose Derdoy and Joyce Hoffmann and Debra King and Joan Siegner and Susan Stewart and Neuschwander-Tetri, {Brent A.} and Judy Thompson and Abrams, {Stephanie H.} and Diana Arceo and Denise Espinosa and Fairly, {Leanel Angeli}",
year = "2019",
month = "5",
day = "1",
doi = "10.1111/apt.15216",
language = "English (US)",
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pages = "1205--1213",
journal = "Alimentary Pharmacology and Therapeutics",
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T1 - Relationship between resolution of non-alcoholic steatohepatitis and changes in lipoprotein sub-fractions

T2 - a post-hoc analysis of the PIVENS trial

AU - the NASH Clinical Research Network

AU - Corey, Kathleen E.

AU - Wilson, Laura A.

AU - Altinbas, Akif

AU - Yates, Katherine P.

AU - Kleiner, David E.

AU - Chung, Raymond T.

AU - Krauss, Ronald M.

AU - Chalasani, Naga

AU - Bringman, Diane

AU - Dasarathy, Srinivasan

AU - Feldstein, Ariel

AU - Hawkins, Carol

AU - Liu, Yao Chang

AU - McCullough, Arthur

AU - Sargent, Ruth

AU - Stager, Margaret

AU - Abdelmalek, Manal

AU - Diehl, Anna Mae

AU - Gottfried, Marcia

AU - Guy, Cynthia

AU - Killenberg, Paul

AU - Kwan, Samantha

AU - Pan, Yi Ping

AU - Piercy, Dawn

AU - Smith, Melissa

AU - Pfeifer, Kimberly

AU - Scheimann, Ann O.

AU - Torbenson, Michael

AU - Bhimalli, Prajakta

AU - Byam, Elizabeth

AU - Cummings, Oscar

AU - Klipsch, Ann

AU - Lee, Lydia

AU - Molleston, Jean

AU - Ragozzino, Linda

AU - Subbarao, Girish

AU - Vuppalanchi, Raj

AU - Barlow, Sarah

AU - Brunt, Elizabeth M.

AU - Derdoy, Jose

AU - Hoffmann, Joyce

AU - King, Debra

AU - Siegner, Joan

AU - Stewart, Susan

AU - Neuschwander-Tetri, Brent A.

AU - Thompson, Judy

AU - Abrams, Stephanie H.

AU - Arceo, Diana

AU - Espinosa, Denise

AU - Fairly, Leanel Angeli

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Background: Dyslipidaemia is frequent in non-alcoholic steatohepatitis (NASH); however, it is unclear if improvement in liver histology is associated with favourable changes in cardiovascular disease (CVD) risk. Aims: To evaluate the relationship of NASH resolution and lipoprotein subfraction levels, markers of endothelial dysfunction, and macrophage activation. Methods: One hundred and seventeen individuals with NASH who participated in the Pioglitazone vs Vitamin E vs Placebo for the Treatment of Nondiabetic Patients with NASH (PIVENS) trial with paired liver biopsies and serum samples available at baseline and after 96 weeks of treatment were included. Participants in the PIVENS trials received vitamin E, pioglitazone, or placebo for 96 weeks. Lipoprotein subfraction levels, intracellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), E-selectin, and sCD163 levels were assessed at baseline and week 96 and their relationship with NASH resolution was examined. Results: Fifty-seven individuals had NASH resolution and 60 individuals did not have resolution of NASH. NASH resolution was associated with favourable changes in lipoprotein subfraction levels compared to those without NASH resolution. Individuals with resolution of NASH had a significantly increased mean peak LDL diameter (ratio of geometric means [96 weeks vs baseline] 1.007 vs 0.996, P = 0.004), and higher frequency of LDL phenotype A (58% vs 33%, P = 0.003) at week 96, after adjustment for relevant co-variates including treatment group. No differences in VCAM, ICAM, E-selectin, or sCD163 levels by NASH resolution were found. Conclusions: NASH resolution is associated with favourable changes in a subset of serum lipoprotein levels. More studies are warranted to understand if these favourable changes are associated with decreased risk of CVD.

AB - Background: Dyslipidaemia is frequent in non-alcoholic steatohepatitis (NASH); however, it is unclear if improvement in liver histology is associated with favourable changes in cardiovascular disease (CVD) risk. Aims: To evaluate the relationship of NASH resolution and lipoprotein subfraction levels, markers of endothelial dysfunction, and macrophage activation. Methods: One hundred and seventeen individuals with NASH who participated in the Pioglitazone vs Vitamin E vs Placebo for the Treatment of Nondiabetic Patients with NASH (PIVENS) trial with paired liver biopsies and serum samples available at baseline and after 96 weeks of treatment were included. Participants in the PIVENS trials received vitamin E, pioglitazone, or placebo for 96 weeks. Lipoprotein subfraction levels, intracellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), E-selectin, and sCD163 levels were assessed at baseline and week 96 and their relationship with NASH resolution was examined. Results: Fifty-seven individuals had NASH resolution and 60 individuals did not have resolution of NASH. NASH resolution was associated with favourable changes in lipoprotein subfraction levels compared to those without NASH resolution. Individuals with resolution of NASH had a significantly increased mean peak LDL diameter (ratio of geometric means [96 weeks vs baseline] 1.007 vs 0.996, P = 0.004), and higher frequency of LDL phenotype A (58% vs 33%, P = 0.003) at week 96, after adjustment for relevant co-variates including treatment group. No differences in VCAM, ICAM, E-selectin, or sCD163 levels by NASH resolution were found. Conclusions: NASH resolution is associated with favourable changes in a subset of serum lipoprotein levels. More studies are warranted to understand if these favourable changes are associated with decreased risk of CVD.

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U2 - 10.1111/apt.15216

DO - 10.1111/apt.15216

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JO - Alimentary Pharmacology and Therapeutics

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