Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.
Hepatology. 2020 Feb;71(2):510-521. doi: 10.1002/hep.30483. Epub 2019 Mar 15.
The lack of reliable, noninvasive methods to diagnose early nonalcoholic steatohepatitis (NASH) is a major unmet need. We aimed to determine the diagnostic accuracy of three-dimensional magnetic resonance elastography (3D-MRE), with shear stiffness measured at 60 Hz, damping ratio at 40 Hz, and magnetic resonance imaging proton density fat fraction (MRI-PDFF) in the detection of NASH in individuals undergoing bariatric surgery. Obese adults at risk for NASH were enrolled between 2015 and 2017 (prospective cohort, n = 88) and 2010 and 2013 (retrospective cohort, n = 87). The imaging protocol consisted of multifrequency 3D-MRE (mf3D-MRE) with shear waves delivered at different frequencies to explore parameters that best correlated with histologic NASH, and MRI-PDFF to estimate steatosis. The prospective cohort was used to establish the optimal mf3D-MRE technical parameters for NASH detection. The two cohorts were then combined to derive predictive models of NASH and disease activity by nonalcoholic fatty liver disease activity score (NAS) using the three imaging parameters that correlated with NASH. A total of 175 patients (median age 45, 81% women, and 81 [46%] with histologic NASH) were used for model derivation. From the complex shear modulus output generated by mf3D-MRE, the damping ratio at 40 Hz and shear stiffness at 60 Hz best correlated with NASH. The fat fraction obtained from MRI-PDFF correlated with steatosis (P < 0.05 for all). These three parameters were fit into a logistic regression model that predicted NASH with cross-validated area under the receiver operating characteristic curve (AUROC) = 0.73, sensitivity = 0.67, specificity = 0.80, positive predictive value = 0.73 and negative predictive value = 0.74, and disease activity by NAS with cross-validated AUROC = 0.82. Conclusion: The mf3D-MRE allows identification of imaging parameters that predict early NASH and disease activity. This imaging biomarker represents a promising alternative to liver biopsy for NASH diagnosis and monitoring. The results provide motivation for further studies in nonbariatric cohorts.
缺乏可靠的、无创的方法来诊断早期非酒精性脂肪性肝炎(NASH)是一个主要的未满足的需求。我们旨在确定三维磁共振弹性成像(3D-MRE)的诊断准确性,该方法以 60 Hz 测量剪切刚度、40 Hz 测量阻尼比以及磁共振成像质子密度脂肪分数(MRI-PDFF),以检测接受减肥手术的个体中的 NASH。2015 年至 2017 年(前瞻性队列,n=88)和 2010 年至 2013 年(回顾性队列,n=87)期间,招募了患有 NASH 风险的肥胖成年人。成像方案包括多频 3D-MRE(mf3D-MRE),以不同频率传递剪切波,以探索与组织学 NASH相关性最佳的参数,并使用 MRI-PDFF 估计脂肪变性。前瞻性队列用于建立用于检测 NASH 的最佳 mf3D-MRE 技术参数。然后,将这两个队列合并,通过非酒精性脂肪性肝病活动评分(NAS)使用与 NASH 相关的三个成像参数,得出 NASH 和疾病活动的预测模型。总共使用 175 名患者(中位年龄 45 岁,81%为女性,81 名[46%]有组织学 NASH)进行模型推导。从 mf3D-MRE 生成的复杂剪切模量输出中,40 Hz 的阻尼比和 60 Hz 的剪切刚度与 NASH 相关性最佳。从 MRI-PDFF 获得的脂肪分数与脂肪变性相关(所有 P<0.05)。将这三个参数拟合到逻辑回归模型中,该模型预测 NASH 的交叉验证受试者工作特征曲线下面积(AUROC)为 0.73,灵敏度为 0.67,特异性为 0.80,阳性预测值为 0.73,阴性预测值为 0.74,以及通过 NAS 预测疾病活动的交叉验证 AUROC 为 0.82。结论:mf3D-MRE 可识别预测早期 NASH 和疾病活动的成像参数。这种成像生物标志物代表了肝活检诊断 NASH 和监测疾病活动的有前途的替代方法。这些结果为在非减肥队列中进行进一步研究提供了动力。