非酒精性脂肪性肝炎患者的 MRE、MRI-PDFF 与肝组织学的纵向相关性：selonsertib 二期临床试验数据分析。
Longitudinal correlations between MRE, MRI-PDFF, and liver histology in patients with non-alcoholic steatohepatitis: Analysis of data from a phase II trial of selonsertib.
机构信息
University of California at San Diego, San Diego, CA, United States.
Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX, United States.
出版信息
J Hepatol. 2019 Jan;70(1):133-141. doi: 10.1016/j.jhep.2018.09.024. Epub 2018 Oct 4.
BACKGROUND & AIMS: Non-invasive tools for monitoring treatment response and disease progression in non-alcoholic steatohepatitis (NASH) are needed. Our objective was to evaluate the utility of magnetic resonance (MR)-based hepatic imaging measures for the assessment of liver histology in patients with NASH.
METHODS
We analyzed data from patients with NASH and stage 2 or 3 fibrosis enrolled in a phase II study of selonsertib. Pre- and post-treatment assessments included centrally read MR elastography (MRE)-estimated liver stiffness, MR imaging-estimated proton density fat fraction (MRI-PDFF), and liver biopsies evaluated according to the NASH Clinical Research Network classification and the non-alcoholic fatty liver disease activity score (NAS).
RESULTS
Among 54 patients with MRE and biopsies at baseline and week 24, 18 (33%) had fibrosis improvement (≥1-stage reduction) after undergoing 24 weeks of treatment with the study drug. The area under the receiver operating characteristic curve (AUROC) of MRE-stiffness to predict fibrosis improvement was 0.62 (95% CI 0.46-0.78) and the optimal threshold was a ≥0% relative reduction. At this threshold, MRE had 67% sensitivity, 64% specificity, 48% positive predictive value, 79% negative predictive value. Among 65 patients with MRI-PDFF and biopsies at baseline and week 24, a ≥1-grade reduction in steatosis was observed in 18 (28%). The AUROC of MRI-PDFF to predict steatosis response was 0.70 (95% CI 0.57-0.83) and the optimal threshold was a ≥0% relative reduction. At this threshold, MRI-PDFF had 89% sensitivity and 47% specificity, 39% positive predictive value, and 92% negative predictive value.
CONCLUSIONS
These preliminary data support the further evaluation of MRE-stiffness and MRI-PDFF for the longitudinal assessment of histologic response in patients with NASH.
LAY SUMMARY
Liver biopsy is a potentially painful and risky method to assess damage to the liver due to non-alcoholic steatohepatitis (NASH). We analyzed data from a clinical trial to determine if 2 methods of magnetic resonance imaging - 1 to measure liver fat and 1 to measure liver fibrosis (scarring) - could potentially replace liver biopsy in evaluating NASH-related liver injury. Both imaging methods were correlated with biopsy in showing the effects of NASH on the liver.
背景与目的
需要非侵入性工具来监测非酒精性脂肪性肝炎（NASH）的治疗反应和疾病进展。我们的目的是评估基于磁共振（MR）的肝脏成像测量在评估 NASH 患者肝脏组织学方面的效用。
方法
我们分析了参加塞隆昔布 II 期研究的 NASH 合并 2 或 3 期纤维化患者的数据。在治疗前和治疗 24 周时，分别进行了中心阅读的磁共振弹性成像（MRE）估计的肝硬度、MR 成像估计的质子密度脂肪分数（MRI-PDFF）和根据 NASH 临床研究网络分类和非酒精性脂肪性肝病活动评分（NAS）评估的肝活检。
结果
在 54 例基线和 24 周时具有 MRE 和活检的患者中，18 例（33%）在接受研究药物治疗 24 周后出现纤维化改善（≥1 期下降）。MRE 硬度预测纤维化改善的受试者工作特征曲线（AUROC）为 0.62（95%CI 0.46-0.78），最佳阈值为≥0%相对减少。在此阈值下，MRE 的敏感性为 67%，特异性为 64%，阳性预测值为 48%，阴性预测值为 79%。在基线和 24 周时具有 MRI-PDFF 和活检的 65 例患者中，18 例（28%）观察到脂肪变性改善≥1 级。MRI-PDFF 预测脂肪变性反应的 AUROC 为 0.70（95%CI 0.57-0.83），最佳阈值为≥0%相对减少。在此阈值下，MRI-PDFF 的敏感性为 89%，特异性为 47%，阳性预测值为 39%，阴性预测值为 92%。
结论
这些初步数据支持进一步评估 MRE 硬度和 MRI-PDFF 用于纵向评估 NASH 患者的组织学反应。
要点总结
肝活检是一种潜在的痛苦和危险的方法，用于评估非酒精性脂肪性肝炎（NASH）引起的肝脏损伤。我们分析了一项临床试验的数据，以确定两种磁共振成像方法 - 一种用于测量肝脂肪，另一种用于测量肝纤维化（瘢痕形成） - 是否可以替代肝活检来评估 NASH 相关的肝损伤。这两种成像方法都与活检相关，表明 NASH 对肝脏的影响。
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