Middleton Michael S, Heba Elhamy R, Hooker Catherine A, Bashir Mustafa R, Fowler Kathryn J, Sandrasegaran Kumar, Brunt Elizabeth M, Kleiner David E, Doo Edward, Van Natta Mark L, Lavine Joel E, Neuschwander-Tetri Brent A, Sanyal Arun, Loomba Rohit, Sirlin Claude B
Department of Radiology, UCSD School of Medicine, San Diego, California.
Department of Radiology, UCSD School of Medicine, San Diego, California.
Gastroenterology. 2017 Sep;153(3):753-761. doi: 10.1053/j.gastro.2017.06.005. Epub 2017 Jun 15.
BACKGROUND & AIMS: We assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference.
We collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo. Hepatic steatosis was assessed at baseline and after 72 weeks of obeticholic acid or placebo by liver biopsy and MRI (scanners from different manufacturers, at 1.5T or 3T). We compared steatosis estimates by PDFF vs histology. Histologic steatosis grade was scored in consensus by a pathology committee. Cross-validated receiver operating characteristic (ROC) analyses were performed.
At baseline, 34% of subjects had steatosis grade 0 or 1, 39% had steatosis grade 2, and 27% had steatosis grade 3; corresponding mean PDFF values were 9.8%±3.7%, 18.1%±4.3%, and 30.1%±8.1%. PDFF classified steatosis grade 0-1 vs 2-3 with an area under the ROC curve (AUROC) of 0.95 (95% CI, 0.91-0.98), and grade 0-2 vs grade 3 steatosis with an AUROC of 0.96 (95% CI, 0.93-0.99). PDFF cut-off values at 90% specificity were 16.3% for grades 2-3 and 21.7% for grade 3, with corresponding sensitivities of 83% and 84%. After 72 weeks' of obeticholic vs placebo, 42% of subjects had a reduced steatosis grade (mean reduction in PDFF from baseline of 7.4%±8.7%), 49% had no change in steatosis grade (mean increase in PDFF from baseline of 0.3%±6.3%), and 9% had an increased steatosis grade (mean increase in PDFF from baseline of 7.7%±6.0%). PDFF change identified subjects with reduced steatosis grade with an AUROC of 0.81 (95% CI, 0.71-0.91) and increased steatosis grade with an AUROC of 0.81 (95% CI, 0.63-0.99). A PDFF reduction of 5.15% identified subjects with reduced steatosis grade with 90% specificity and 58% sensitivity, whereas a PDFF increase of 5.6% identified those with increased steatosis grade with 90% specificity and 57% sensitivity.
Based on data from a phase 2 randomized controlled trial of adults with NASH, PDFF estimated by MRI scanners of different field strength and at different sites, accurately classifies grades and changes in hepatic steatosis when histologic analysis of biopsies is used as a reference.
在一项多中心研究中，我们以中心组织学为参照，评估了磁共振成像（MRI）质子密度脂肪分数（PDFF）在非酒精性脂肪性肝炎（NASH）成人患者肝脂肪变性分级及肝脂肪变性变化方面的诊断性能。
我们收集了113例参与多中心、随机、双盲、安慰剂对照2b期试验的NASH成人患者的数据，以横断面和纵向比较奥贝胆酸与安慰剂的疗效。在基线以及接受奥贝胆酸或安慰剂治疗72周后，通过肝活检和MRI（来自不同制造商的1.5T或3T扫描仪）评估肝脂肪变性情况。我们比较了通过PDFF得出的脂肪变性评估结果与组织学结果。组织学脂肪变性分级由病理委员会进行一致性评分。进行了交叉验证的受试者操作特征（ROC）分析。
在基线时，34%的受试者脂肪变性分级为0或1级，39%为2级，27%为3级；相应的平均PDFF值分别为9.8%±3.7%、18.1%±4.3%和30.1%±8.1%。PDFF对0 - 1级与2 - 3级脂肪变性的分类，其ROC曲线下面积（AUROC）为0.95（95%CI，0.91 - 0.98），对0 - 2级与3级脂肪变性的分类，AUROC为0.96（95%CI，0.93 - 0.99）。2 - 3级脂肪变性在90%特异性时的PDFF临界值为16.3%，3级为21.7%，相应的敏感性分别为83%和84%。与安慰剂相比，接受奥贝胆酸治疗72周后，42%的受试者脂肪变性分级降低（PDFF较基线平均降低7.4%±8.7%），49%的受试者脂肪变性分级无变化（PDFF较基线平均增加0.3%±6.3%），9%的受试者脂肪变性分级增加（PDFF较基线平均增加7.7%±6.0%）。PDFF变化对脂肪变性分级降低的受试者的识别，AUROC为0.81（95%CI，0.71 - 0.91），对脂肪变性分级增加的受试者的识别，AUROC为0.81（95%CI，0.63 - 0.99）。PDFF降低5.15%对脂肪变性分级降低的受试者的识别，特异性为90%，敏感性为58%，而PDFF增加5.6%对脂肪变性分级增加的受试者的识别，特异性为90%，敏感性为57%。
基于一项NASH成人患者的2期随机对照试验数据，当以活检的组织学分析为参照时，由不同场强和不同部位的MRI扫描仪估算的PDFF能准确地对肝脂肪变性分级及变化进行分类。
