Noninvasive Tests Accurately Identify Advanced Fibrosis due to NASH: Baseline Data From the STELLAR Trials
Noninvasive Tests Accurately Identify Advanced Fibrosis due to NASH: Baseline Data From the STELLAR Trials
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DOI：
10.1002/hep.30842
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发表时间：
2019-08-19
期刊：
影响因子：
13.5
通讯作者：
Younossi, Zobair M.
中科院分区：
文献类型：
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作者：
Anstee, Quentin M.;Lawitz, Eric J.;Younossi, Zobair M.
需要准确的无创检测 (NIT) 来取代肝活检，以识别非酒精性脂肪性肝炎 (NASH) 引起的晚期纤维化。我们分析了 Selonsertib 两项 3 期试验的筛查数据，以评估 NIT 区分晚期纤维化的能力。 STELLAR 研究纳入了桥接性纤维化和代偿性肝硬化患者，集中读取活检样本，并根据 NASH 临床研究网络分类进行分期。我们探讨了纤维化阶段和 NIT 之间的关联，包括非酒精性脂肪性肝病纤维化评分 (NFS)、纤维化 4 (FIB-4) 指数、增强型肝纤维化 (ELF) 测试以及振动控制瞬时弹性成像 (LS by VCTE) 检测的肝脏硬度。使用受试者工作特征曲线 (AUROC) 下的面积和重复 100 次的 5 倍交叉验证来评估这些测试单独或组合区分晚期纤维化的性能。在这些试验筛选的 4,404 名患者中，3,202 名患者具有可评估的活检数据：940 名患者患有 F0-F2 纤维化，2,262 名患者患有 F3-F4 纤维化。 F0-F2 与 F3-F4 纤维化患者的 NIT 中值之间存在显着差异：NFS 为 -0.972 与 0.318，FIB-4 为 1.18 与 2.20，ELF 为 9.22 与 10.39，LS 为 8.8 与 16.5 kPa（均 P < 0.001）。 AUROC 范围为 0.75 至 0.80，以区分晚期纤维化。 FIB-4 随后通过 VCTE 或 ELF 进行 LS 测试，对于具有不确定值（FIB-4 在 1.3 和 2.67 之间）的测试保持了可接受的性能，同时降低了不确定结果的发生率。结论：在考虑参加临床试验的患者中，单独或联合 NIT 可以减少肝活检的需要，以区分 NASH 引起的晚期纤维化。这些测试对一般筛查的预测价值需要在现实世界人群中得到确认。
Accurate noninvasive tests (NITs) are needed to replace liver biopsy for identifying advanced fibrosis caused by nonalcoholic steatohepatitis (NASH). We analyzed screening data from two phase 3 trials of selonsertib to assess the ability of NITs to discriminate advanced fibrosis. Centrally read biopsies from the STELLAR studies, which enrolled patients with bridging fibrosis and compensated cirrhosis, were staged according to the NASH Clinical Research Network classification. We explored associations between fibrosis stage and NITs, including the nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 (FIB-4) index, Enhanced Liver Fibrosis (ELF) test, and liver stiffness by vibration-controlled transient elastography (LS by VCTE). The performance of these tests to discriminate advanced fibrosis, either alone or in combinations, was evaluated using areas under the receiver operating characteristic curve (AUROCs) with 5-fold cross-validation repeated 100 times. Of the 4,404 patients screened for these trials, 3,202 had evaluable biopsy data: 940 with F0-F2 fibrosis and 2,262 with F3-F4 fibrosis. Significant differences between median values of NITs for patients with F0-F2 versus F3-F4 fibrosis were observed: -0.972 versus 0.318 for NFS, 1.18 versus 2.20 for FIB-4, 9.22 versus 10.39 for ELF, and 8.8 versus 16.5 kPa for LS by VCTE (all P < 0.001). AUROCs ranged from 0.75 to 0.80 to discriminate advanced fibrosis. FIB-4 followed by an LS by VCTE or ELF test in those with indeterminate values (FIB-4 between 1.3 and 2.67) maintained an acceptable performance while reducing the rate of indeterminate results. Conclusion: Among patients being considered for enrollment into clinical trials, NITs alone or in combination can reduce the need for liver biopsy to discriminate advanced fibrosis caused by NASH. The predictive value of these tests for general screening will require confirmation in a real-world population.