Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis
Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis
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DOI：
10.1177/1756283x16656735
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发表时间：
2016-09-01
影响因子：
4.2
通讯作者：
Loomba, Rohit
中科院分区：
文献类型：
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作者：
Patel, Janki;Bettencourt, Ricki;Loomba, Rohit
背景：在非酒精性脂肪性肝炎(NASH)临床试验中，磁共振成像-估计质子密度-脂肪分数(MRI-PDFF)已被证明是一种基于成像的无创、准确和可重复性的生物标志物，用于评估脂肪变性和治疗反应。然而，在NASH临床试验的背景下，没有与组织学反应相对应的MRI-PDFF减少的幅度的数据。这项研究的目的是定量比较NASH患者中组织学有效者和组织学无应答者的MRI-PDFF减少的幅度。方法：这项研究是对Mozart试验的二次分析，该试验包括50名经活检证实的NASH患者，随机给予依折麦布10 mg/天口服或安慰剂治疗24周。主要目的是对组织学有效者[定义为非酒精性脂肪性肝病(NAFLD)活动评分(NAS)在不加重纤维化的情况下降低2分]和无应答者进行面对面的比较分析，并通过MRI-PDFF测量相应的肝脏脂肪含量的定量变化。结果：在35名在治疗开始和结束时接受配对肝活检和MRI-PDFF评估的患者中，有10人表现出组织学反应。与组织学无反应者相比，组织学有反应者的MRI-PDF值分别为-4.1%4.9和-0.6+/-4.1(p<；0.04)，平均相对百分比变化分别为-29.3%+/-33.0和+2.0%+/-24.0(p<；0.004)。结论：利用配对的MRI-PDFF值和肝脏组织学数据，我们证明在MRI-PDFF值上肝脏脂肪相对减少29%与NASH的组织学反应有关。经过独立研究小组的外部验证后，这些结果可以被纳入未来NASH临床试验的设计中，特别是那些利用MRI-PDFF量化的肝脏脂肪变化作为治疗终点的试验。
Background: Magnetic resonance imaging-estimated proton-density-fat-fraction (MRI-PDFF) has been shown to be a noninvasive, accurate and reproducible imaging-based biomarker for assessing steatosis and treatment response in nonalcoholic steatohepatitis (NASH) clinical trials. However, there are no data on the magnitude of MRI-PDFF reduction corresponding to histologic response in the setting of a NASH clinical trial. The aim of this study was to quantitatively compare the magnitude of MRI-PDFF reduction between histologic responders versus histologic nonresponders in NASH patients.Methods: This study is a secondary analysis of the MOZART trial, which included 50 patients with biopsy-proven NASH randomized to ezetimibe 10 mg/day orally or placebo for 24 weeks. The primary aim was to perform a head-to-head comparative analysis of histologic responders [defined as a 2-point reduction in the nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) without worsening fibrosis] versus nonresponders, and the corresponding quantitative change in liver fat content measured via MRI-PDFF.Results: Of the 35 patients who underwent paired liver biopsy and MRI-PDFF assessment at the beginning and end of treatment, 10 demonstrated a histologic response. Compared with histologic nonresponders, histologic responders had a statistically significant reduction in MRI-PDFF of -4.1% 4.9 versus -0.6 +/- 4.1 (p < 0.04) with a mean relative percent change of -29.3% +/- 33.0 versus +2.0% +/- 24.0 (p < 0.004), respectively.Conclusions: Utilizing paired MRI-PDFF and liver histology data, we demonstrate that a relative reduction of 29% in liver fat on MRI-PDFF is associated with a histologic response in NASH. After external validation by independent research groups, these results can be incorporated into designing future NASH clinical trials, especially those utilizing change in hepatic fat quantified by MRI-PDFF, as a treatment endpoint.