Division of Gastroenterology and Hepatology, Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Department of Public Health Sciences, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Liver Center, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Cancer Institute, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
Department of Medicine, University of California, San Diego, La Jolla, California.
Clin Gastroenterol Hepatol. 2021 Nov;19(11):2274-2283.e5. doi: 10.1016/j.cgh.2020.08.061. Epub 2020 Aug 31.
BACKGROUND & AIMS: Magnetic resonance imaging proton density fat fraction (MRI-PDFF) offers promise as a non-invasive biomarker of treatment response in early-phase nonalcoholic steatohepatitis (NASH) trials. We performed a systematic review to quantify the association between a ≥ 30% reduction in MRI-PDFF and histologic response in NASH.
We searched the Cochrane Library, Embase, Medline and trial registries through May 2020 for early-phase clinical trials that incorporated MRI-PDFF and examined histologic response following intervention in adults with NASH. Subjects were classified as MRI-PDFF responders (relative decline in liver fat ≥30%) or non-responders (relative decline in liver fat <30%). MRI-PDFF responders versus non-responders were compared. Primary outcome was histologic response defined as a 2-point improvement in NAFLD Activity Score with at least 1-point improvement in lobular inflammation or ballooning. Secondary outcome was NASH resolution. Proportions and random effects odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated.
Seven studies met inclusion criteria, comprising 346 subjects (median age 51 years; 59% female; 46% with diabetes). MRI-PDFF responders were significantly more likely to have a histologic response (51% vs 14%, P < .001; OR 6.98, 95% CI 2.38-20.43, P < .001) and NASH resolution (41% vs 7%, P < .001; OR 5.45, 95% CI 1.53-19.46, P = .009) compared to non-responders.
This meta-analysis demonstrates that a ≥30% relative decline in MRI-PDFF is associated with higher odds of histologic response and NASH resolution. These results support the use of MRI-PDFF in non-invasive monitoring of treatment response in early-phase NASH clinical trials and provide helpful data for sample-size estimation for histology-based assessment.
磁共振成像质子密度脂肪分数（MRI-PDFF）有望成为非酒精性脂肪性肝炎（NASH）早期临床试验中治疗反应的非侵入性生物标志物。我们进行了一项系统评价，以量化 MRI-PDFF 降低≥30%与 NASH 组织学反应之间的相关性。
我们通过 Cochrane 图书馆、Embase、Medline 和试验注册处搜索了截至 2020 年 5 月的早期临床试验，这些试验纳入了 MRI-PDFF，并检查了 NASH 成人干预后组织学反应。受试者被分为 MRI-PDFF 应答者（肝脏脂肪相对下降≥30%）或非应答者（肝脏脂肪相对下降<30%）。比较 MRI-PDFF 应答者和非应答者。主要结局是组织学反应，定义为 NAFLD 活动评分至少改善 2 分，且至少有 1 分改善肝小叶炎症或气球样变。次要结局是 NASH 缓解。计算了比例和随机效应比值比（OR）及其相应的 95%置信区间（CI）。
7 项研究符合纳入标准，共纳入 346 例患者（中位年龄 51 岁；59%为女性；46%患有糖尿病）。MRI-PDFF 应答者发生组织学反应的可能性显著更高（51% vs 14%，P<0.001；OR 6.98，95% CI 2.38-20.43，P<0.001）和 NASH 缓解（41% vs 7%，P<0.001；OR 5.45，95% CI 1.53-19.46，P=0.009）的可能性显著更高。
这项荟萃分析表明，MRI-PDFF 降低≥30%与组织学反应和 NASH 缓解的可能性更高相关。这些结果支持在 NASH 早期临床试验中使用 MRI-PDFF 进行非侵入性治疗反应监测，并为基于组织学评估的样本量估计提供了有用的数据。
