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.
Journal Article (Letter)
UNLABELLED: 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] × 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.
Full Text
Duke Authors
Cited Authors
- Bell, LN; Wang, J; Muralidharan, S; Chalasani, S; Fullenkamp, AM; Wilson, LA; Sanyal, AJ; Kowdley, KV; Neuschwander-Tetri, BA; Brunt, EM; McCullough, AJ; Bass, NM; Diehl, AM; Unalp-Arida, A; Chalasani, N; Nonalcoholic Steatohepatitis Clinical Research Network,
Published Date
- October 2012
Published In
Volume / Issue
- 56 / 4
Start / End Page
- 1311 - 1318
PubMed ID
- 22532269
Pubmed Central ID
- 22532269
Electronic International Standard Serial Number (EISSN)
- 1527-3350
Digital Object Identifier (DOI)
- 10.1002/hep.25805
Language
- eng
Conference Location
- United States