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Adipose tissue insulin resistance may improve liver histology in patients with NASH

Improved liver histology was associated with an increase in adipose tissue insulin resistance among patients with NASH, independent of treatment with vitamin E or pioglitazone, in a recent study.

In a follow-up to the Pioglitazone vs. Vitamin E. vs. Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial, researchers examined the adipose tissue insulin resistance (Adipo-IR) of patients with NASH. Patients were randomly assigned to receive either pioglitazone (n=80), vitamin E (n=84) or placebo (n=82) and were evaluated at baseline and after 16 and 96 weeks of treatment.

Adipo-IR at baseline was not significantly different from placebo in the pioglitazone (P=.29) or vitamin E (P=.34) groups. Patients in the pioglitazone group experienced a significant Adipo-IR reduction at 16 weeks (mean change –15.7 compared with –1.91 in the placebo group, P=.02), but not at 96 weeks (–3.25 compared with –4.28, P=.31). No significant difference from the placebo group was observed in the vitamin E group at 16 weeks (mean change 2.81, P=.71) or 96 weeks (mean change 11.2, P=.8).

Multivariate analysis indicated Adipo-IR increase at 96 weeks was associated with histological improvements including hepatocellular ballooning (P=.03), fibrosis (P=.004) and NAFLD activity score (P=.01), along with an increase in BMI (P=.002). Associations also were observed between Adipo-IR and female sex (P<.001), higher total cholesterol levels (P=.03), high BMI (P=.004) and higher glucose levels (P=.001) at 96 weeks.

Naga Chalasani

“An earlier study … suggested that pioglitazone’s favorable effect on liver histology in NASH is mediated through its effect on adipose tissue insulin resistance,” Naga Chalasani, MD, director of the gastroenterology and hepatology division at Indiana University School of Medicine in Indianapolis, told Healio.com. “The prevailing view has been that modifying insulin resistance, specifically adipose tissue insulin resistance, is essential to improve NASH. However, both pioglitazone and vitamin E improved NASH without necessarily improving adipose tissue insulin resistance.”

The researchers also indicated that Adipo-IR could be a potential biomarker for changes in liver histology among NASH patients, and that the association between fibrosis and Adipo-IR merits further study.