Kathleen E Corey1, Laura A Wilson2, Akif Altinbas1, Katherine P Yates2, David E Kleiner3, Raymond T Chung1, Ronald M Krauss4, Naga Chalasani5. 1. Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts. 2. Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 3. Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 4. Children's Hospital Oakland Research Institute, Oakland, California. 5. Indiana University School of Medicine, Indianapolis, Indiana.
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 thePioglitazone 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.
RCT Entities:
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 NondiabeticPatients 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.
Authors: S J Hwang; C M Ballantyne; A R Sharrett; L C Smith; C E Davis; A M Gotto; E Boerwinkle Journal: Circulation Date: 1997-12-16 Impact factor: 29.690
Authors: Samia Mora; Michael P Caulfield; Jay Wohlgemuth; Zhihong Chen; H Robert Superko; Charles M Rowland; Robert J Glynn; Paul M Ridker; Ronald M Krauss Journal: Circulation Date: 2015-09-25 Impact factor: 29.690
Authors: Silvia Sookoian; Gustavo O Castaño; Adriana L Burgueño; María Soledad Rosselli; Tomas Fernández Gianotti; Pablo Mallardi; Julio San Martino; Carlos Jose Pirola Journal: Atherosclerosis Date: 2009-10-13 Impact factor: 5.162
Authors: William C Cromwell; James D Otvos; Michelle J Keyes; Michael J Pencina; Lisa Sullivan; Ramachandran S Vasan; Peter W F Wilson; Ralph B D'Agostino Journal: J Clin Lipidol Date: 2007-12 Impact factor: 4.766
Authors: M Adiels; M-R Taskinen; C Packard; M J Caslake; A Soro-Paavonen; J Westerbacka; S Vehkavaara; A Häkkinen; S-O Olofsson; H Yki-Järvinen; J Borén Journal: Diabetologia Date: 2006-02-04 Impact factor: 10.122
Authors: Kiran Musunuru; Marju Orho-Melander; Michael P Caulfield; Shuguang Li; Wael A Salameh; Richard E Reitz; Göran Berglund; Bo Hedblad; Gunnar Engström; Paul T Williams; Sekar Kathiresan; Olle Melander; Ronald M Krauss Journal: Arterioscler Thromb Vasc Biol Date: 2009-09-03 Impact factor: 8.311
Authors: Ville T Männistö; Marko Simonen; Pasi Soininen; Mika Tiainen; Antti J Kangas; Dorota Kaminska; Sari Venesmaa; Pirjo Käkelä; Vesa Kärjä; Helena Gylling; Mika Ala-Korpela; Jussi Pihlajamäki Journal: J Lipid Res Date: 2014-10-24 Impact factor: 5.922
Authors: Michele Mietus-Snyder; Nisha Narayanan; Ronald M Krauss; Kirsten Laine-Graves; Joyce C McCann; Mark K Shigenaga; Tara H McHugh; Bruce N Ames; Jung H Suh Journal: PLoS One Date: 2020-10-20 Impact factor: 3.240
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