摘要 PIVENS（即吡格列酮vs维生素E vs安慰剂治疗无糖尿病的非酒精性脂肪性肝炎[NASH]患者）试验表明，吡格列酮与维生素E能不同程度的改善肝脏组织学，但其作用机制不明。在PIVENS试验期间，我们实施了一项研究以检测脂肪组织胰岛素抵抗（脂肪IR）的变化，以及其与组织学终点之间的关系。在基线时，以及治疗16和96周之后，计算脂肪IR（空腹游离脂肪酸[NEFAs]×空腹胰岛素）。与安慰剂比较，基线时维生素E组（P=0.34）或吡格列酮组（P=0.29）脂肪IR无差异。基线时脂肪IR与纤维化评分显著相关（P=0.02），但与其他组织学特征及非酒精性脂肪性肝病（NAFLD）活动评分（NAS）无关。16周后，与安慰剂相比，吡格列酮组脂肪IR显著降低（-15.7比-1.91，P=0.02），但在96周这一作用并未持续（-3.25比-4.28，P=0.31）。与安慰剂相比，维生素E组无论是在16周（P=0.70）还是96周（P=0.85）脂肪IR均无显著改变。在16周时的脂肪IR变化与96周时的任何组织学参数变化均无关，但在96周时的脂肪IR改善与气球样变（P=0.03）、纤维化（P=0.004）和NAS（P=0.01）改善显著相关。结论：维生素E改善肝脏组织学，这独立于脂肪IR之外，吡格列酮治疗能够迅速改善脂肪IR，但这一作用并不持久，脂肪IR变化与肝脏组织学包括纤维化变化相关。
Abstract
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.
江西省景德镇市第三人民医院消化内科 朱晓佳 杨力 摘译
Hepatology. 2012 ,56(4):1311-1318.
Hepatology. 2012 ,56(4):1311-1318.
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
Abstract
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.
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