肝硬度阈值可预测桥接纤维化和肝硬化的疾病进展和临床结

StephenW

肝硬度阈值可预测桥接纤维化和肝硬化的疾病进展和临床结果

    http://orcid.org/0000-0002-4845-9991Rohit Loomba1,2, http://orcid.org/0000-0002-5165-5061Daniel Q. Huang2,3,4, Arun J Sanyal5, Quentin Mark Anstee6, http://orcid.org/0000-0002-1275-6425Michael Trauner7, Eric J Lawitz8, Dora Ding9, Lily Ma9, Catherine Jia9, Andrew Billin9, Ryan S Huss9, Chuhan Chung9, Zachary Goodman10, http://orcid.org /0000-0003-2215-9410Vincent Wai-Sun Wong11, Takeshi Okanoue12, Manuel Romero-Gómez13, Manal F Abdelmalek14, Andrew Muir15, Nezam Afdhal16, Jaime Bosch17, Stephen Harrison18,19, http://orcid.org/0000-0001 -9313-577XZobair M Younossi20, Robert P Myers9

    与美国加利福尼亚州拉霍亚市加州大学圣地亚哥分校 Rohit Loomba 教授的通信； [email protected]

抽象的

目的 在回顾性研究中，振动控制瞬时弹性成像 (VCTE) 的肝脏硬度 (LS) 与非酒精性脂肪性肝炎 (NASH) 患者的肝脏失代偿风险相关，但活检证实的晚期纤维化队列的前瞻性数据是有限的。我们旨在通过 VCTE 建立 LS 阈值，以预测 NASH 所致肝硬化患者中桥接纤维化和肝失代偿患者进展为肝硬化。

设计 我们使用了来自晚期纤维化（F3-F4）参与者的四项 selonertib 和 simtuzumab 随机安慰剂对照试验的数据。试验因缺乏疗效而终止。肝纤维化在基线和第 48 周（selonsertib 研究）或第 96 周（simtuzumab 研究）集中分期。使用 Cox 比例风险回归分析确定 VCTE 的 LS 与疾病进展之间的关联。

结果 16% (103/664) 的桥接纤维化参与者进展为肝硬化，4% (27/734) 的基线肝硬化参与者发生了经裁定的肝脏相关事件。预测肝硬化进展的最佳基线 LS 阈值是 ≥16.6 kPa，预测肝脏相关事件的最佳基线 LS 阈值是 ≥30.7 kPa。基线 LS ≥16.6 kPa（调整后 HR 3.99；95% CI 2.66 至 5.98，p<0.0001）和 ≥5 kPa（和 ≥20%）增加（调整后 HR 1.98；95% CI 1.20 至 3.26，p=0.008）桥接纤维化参与者进展为肝硬化的独立预测因子，而基线 LS ≥ 30.7 kPa（调整后的 HR 10.13，95% CI 4.38 至 23.41，p<0.0001）预测肝硬化参与者的肝脏相关事件。

结论本研究中确定的 LS 阈值可能有助于 NASH 晚期纤维化患者的风险分层。
数据可用性声明

没有可用的数据。

http://dx.doi.org/10.1136/gutjnl-2022-327777

StephenW

Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis

    http://orcid.org/0000-0002-4845-9991Rohit Loomba1,2, http://orcid.org/0000-0002-5165-5061Daniel Q. Huang2,3,4, Arun J Sanyal5, Quentin Mark Anstee6, http://orcid.org/0000-0002-1275-6425Michael Trauner7, Eric J Lawitz8, Dora Ding9, Lily Ma9, Catherine Jia9, Andrew Billin9, Ryan S Huss9, Chuhan Chung9, Zachary Goodman10, http://orcid.org/0000-0003-2215-9410Vincent Wai-Sun Wong11, Takeshi Okanoue12, Manuel Romero-Gómez13, Manal F Abdelmalek14, Andrew Muir15, Nezam Afdhal16, Jaime Bosch17, Stephen Harrison18,19, http://orcid.org/0000-0001-9313-577XZobair M Younossi20, Robert P Myers9

    Correspondence to Professor Rohit Loomba, University of California San Diego, La Jolla, California, USA; [email protected]

Abstract

Objective In retrospective studies, liver stiffness (LS) by vibration-controlled transient elastography (VCTE) is associated with the risk of liver decompensation in patients with non-alcoholic steatohepatitis (NASH), but prospective data in biopsy-confirmed cohorts with advanced fibrosis are limited. We aimed to establish thresholds for LS by VCTE that predict progression to cirrhosis among patients with bridging fibrosis and hepatic decompensation among patients with cirrhosis due to NASH.

Design We used data from four randomised placebo-controlled trials of selonsertib and simtuzumab in participants with advanced fibrosis (F3–F4). The trials were discontinued due to lack of efficacy. Liver fibrosis was staged centrally at baseline and week 48 (selonsertib study) or week 96 (simtuzumab study). Associations between LS by VCTE with disease progression were determined using Cox proportional hazards regression analysis.

Results Progression to cirrhosis occurred in 16% (103/664) of participants with bridging fibrosis and adjudicated liver-related events occurred in 4% (27/734) of participants with baseline cirrhosis. The optimal baseline LS thresholds were ≥16.6 kPa for predicting progression to cirrhosis, and ≥30.7 kPa for predicting liver-related events. Baseline LS ≥16.6 kPa (adjusted HR 3.99; 95% CI 2.66 to 5.98, p<0.0001) and a ≥5 kPa (and ≥20%) increase (adjusted HR 1.98; 95% CI 1.20 to 3.26, p=0.008) were independent predictors of progression to cirrhosis in participants with bridging fibrosis, while baseline LS ≥30.7 kPa (adjusted HR 10.13, 95% CI 4.38 to 23.41, p<0.0001) predicted liver-related events in participants with cirrhosis.

Conclusion The LS thresholds identified in this study may be useful for risk stratification of NASH patients with advanced fibrosis.
Data availability statement

No data are available.

http://dx.doi.org/10.1136/gutjnl-2022-327777