Relationship between adipose tissue insulin resistance and liver histology in nonalcoholic steatohepatitis: A pioglitazone versus vitamin E versus placebo for the treatment of nondiabetic patients with nonalcoholic steatohepatitis trial follow-up study

被引：105

作者：

Bell, Lauren N. ^{[1
]}

Wang, Jiangxia ^{[2
]}

Muralidharan, Sriya ^{[1
]}

Chalasani, Sadhana ^{[1
]}

Fullenkamp, Allison M. ^{[1
]}

Wilson, Laura A. ^{[2
]}

Sanyal, Arun J. ^{[3
]}

Kowdley, Kris V. ^{[4
]}

Neuschwander-Tetri, Brent A. ^{[5
]}

Brunt, Elizabeth M. ^{[6
]}

McCullough, Arthur J. ^{[7
]}

Bass, Nathan M. ^{[8
]}

Diehl, Anna Mae ^{[9
]}

Unalp-Arida, Aynur ^{[2
]}

Chalasani, Naga ^{[1
]}

机构：

[1] Indiana Univ, Div Gastroenterol Hepatol, Indianapolis, IN 46204 USA

[2] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA

[3] Virginia Commonwealth Univ, Richmond, VA USA

[4] Virginia Mason Med Ctr, Seattle, WA 98101 USA

[5] St Louis Univ, Sch Med, St Louis, MO USA

[6] Washington Univ, Sch Med, St Louis, MO USA

[7] Cleveland Clin Fdn, Cleveland, OH 44195 USA

[8] Univ Calif San Francisco, San Francisco, CA 94143 USA

[9] Duke Univ, Sch Med, Durham, NC USA

[10] NIDDKD, Bethesda, MD 20892 USA

来源：

HEPATOLOGY | 2012年 / 56卷 / 04期

关键词：

DISEASE; MECHANISMS; CIRRHOSIS; DESIGN; FAT;

D O I：

10.1002/hep.25805

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

The PIVENS (Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis [NASH]) trial demonstrated that pioglitazone and vitamin E improved liver histology to varying degrees, but the mechanisms are unknown. We conducted a study to examine the changes in adipose tissue insulin resistance (Adipo-IR) during the PIVENS trial and its relationship to histological endpoints. Adipo-IR (fasting nonesterified fatty acids [NEFAs] x fasting insulin) was calculated at baseline and after 16 and 96 weeks of therapy. Compared to placebo, the baseline Adipo-IR was not different in either the vitamin E group (P = 0.34) or the pioglitazone group (P = 0.29). Baseline Adipo-IR was significantly associated with fibrosis score (P = 0.02), but not with other histological features or nonalcoholic fatty liver disease (NAFLD) activity score (NAS). After 16 weeks, compared to placebo, the pioglitazone group had a significant reduction in Adipo-IR (-15.7 versus -1.91; P = 0.02), but this effect did not persist at 96 weeks (-3.25 versus -4.28; P = 0.31). Compared to placebo, Adipo-IR in the vitamin E group did not change significantly either after 16 weeks (P = 0.70) or after 96 weeks (P = 0.85). Change in Adipo-IR at week 16 was not associated with changes in any histological parameters at week 96, but improvement in Adipo-IR at week 96 was significantly associated with improvement in ballooning (P = 0.03), fibrosis (P = 0.004), and NAS (P = 0.01). Conclusion: Vitamin E improved liver histology independent of changes in Adipo-IR, and pioglitazone treatment acutely improved Adipo-IR, but this was not sustained. Changes in Adipo-IR were associated with changes in liver histology, including fibrosis. (HEPATOLOGY 2012)

引用

页码：1311 / 1318

页数：8

共 15 条

[1]

A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis [J].