Division of Gastroenterology/Hepatology, Indiana University, Indianapolis, IN 46202, USA.
Hepatology. 2012 Oct;56(4):1311-8. doi: 10.1002/hep.25805. Epub 2012 Aug 21.
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).
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.
PIVENS（吡格列酮与维生素 E 治疗非酒精性脂肪性肝炎[NASH]的非糖尿病患者的安慰剂对照）试验表明，吡格列酮和维生素 E 在不同程度上改善了肝脏组织学，但机制尚不清楚。我们进行了一项研究，以检查 PIVENS 试验期间脂肪组织胰岛素抵抗（Adipo-IR）的变化及其与组织学终点的关系。在基线和治疗 16 周和 96 周时计算 Adipo-IR（空腹非酯化脂肪酸[NEFAs]×空腹胰岛素）。与安慰剂相比，维生素 E 组（P = 0.34）或吡格列酮组（P = 0.29）的基线 Adipo-IR 没有差异。基线 Adipo-IR 与纤维化评分显著相关（P = 0.02），但与其他组织学特征或非酒精性脂肪性肝病（NAFLD）活动评分（NAS）无关。治疗 16 周后，与安慰剂相比，吡格列酮组的 Adipo-IR 显著降低（-15.7 对-1.91；P = 0.02），但这种作用在 96 周时并未持续（-3.25 对-4.28；P = 0.31）。与安慰剂相比，维生素 E 组的 Adipo-IR 在 16 周时（P = 0.70）和 96 周时（P = 0.85）也没有明显变化。第 16 周时 Adipo-IR 的变化与第 96 周时任何组织学参数的变化无关，但第 96 周时 Adipo-IR 的改善与气球样变（P = 0.03）、纤维化（P = 0.004）和 NAS（P = 0.01）的改善显著相关。
维生素 E 改善肝脏组织学独立于 Adipo-IR 的变化，吡格列酮治疗急性改善 Adipo-IR，但这种作用不能持续。Adipo-IR 的变化与肝脏组织学变化相关，包括纤维化。
