Dipartimento Di Promozione Della Salute, Section of Gastroenterology and Hepatology, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Italy.
Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Italy.
Hepatology. 2024 Apr 1;79(4):912-925. doi: 10.1097/HEP.0000000000000616. Epub 2023 Oct 2.
International regulatory agencies recommend testing drug therapy for patients with noncirrhotic high-risk metabolic dysfunction-associated steatohepatitis (MASH) because they are at risk of liver-related events (LRE). We aimed to compare the risk of LRE in patients with MASLD stratified for F2-F4 fibrosis and MASH.
Overall, 1938 consecutive patients with biopsy-proven MASLD were enrolled. High-risk MASH was defined as MASH with F2-F4 fibrosis. LSM was measured by transient elastography. LRE were recorded during follow-up. Cox multivariate models were used to assess the association between high-risk MASH or F2-F4 fibrosis without MASH, of LSM (≥8 or ≥10 Kpa), and of AGILE 3+ with LRE. The diagnostic performance for the prediction of LRE was assessed using the area under the receiver operating characteristic curves. The observed 5-year actuarial rate of LRE was 0.4%, 0.2%, 5.1%, and 6.6% in patients with F0-F1 fibrosis without MASH, F0-F1 fibrosis with MASH, F2-F4 fibrosis without MASH, and high-risk MASH, respectively. At multivariate Cox regression analysis using F0-F1 fibrosis without MASH as a reference, both F2-F4 fibrosis without MASH [adjusted HR (aHR) 9.96] and high-risk MASH (aHR 10.14) were associated with LRE. In the 1074 patients with available LSM, LSM ≥ 10 kPa (aHR 6.31) or AGILE 3+ > 0.67 (aHR 27.45) independently predicted the development of LRE and had similarly acceptable 5-year area under the receiver operating characteristic to high-risk MASH and F2-F4 fibrosis (0.772, 0.818, 0.739, and 0.780, respectively).
The risk of LRE is similar in patients with high-risk MASH and with F2-F4 fibrosis without MASH. The use of LSM ≥ 10 kPa or AGILE 3+ > 0.67 could be an accurate option to identify patients with MASLD worthy to be included in clinical trials.
国际监管机构建议对非肝硬化高危代谢功能相关脂肪性肝炎（MASH）患者进行药物治疗检测，因为他们有发生肝脏相关事件（LRE）的风险。我们旨在比较伴有 F2-F4 纤维化和 MASH 的 MASLD 患者的 LRE 风险。
共纳入 1938 例经肝活检证实的 MASLD 连续患者。高危 MASH 定义为伴有 F2-F4 纤维化的 MASH。通过瞬时弹性成像测量 LSM。在随访期间记录 LRE。使用 Cox 多变量模型评估高风险 MASH 或无 MASH 的 F2-F4 纤维化、LSM（≥8 或≥10kPa）和 AGILE 3+与 LRE 之间的关系。使用受试者工作特征曲线下面积评估预测 LRE 的诊断性能。在无 MASH 的 F0-F1 纤维化、无 MASH 的 F2-F4 纤维化、无 MASH 的高风险 MASH和高风险 MASH 的患者中，观察到的 5 年累计 LRE 发生率分别为 0.4%、0.2%、5.1%和 6.6%。在使用无 MASH 的 F0-F1 纤维化作为参考的多变量 Cox 回归分析中，无 MASH 的 F2-F4 纤维化[调整后的 HR（aHR）9.96]和高风险 MASH（aHR 10.14）均与 LRE 相关。在 1074 例可获得 LSM 的患者中，LSM≥10kPa（aHR 6.31）或 AGILE 3+>0.67（aHR 27.45）独立预测 LRE 的发生，且与高风险 MASH 和 F2-F4 纤维化的 5 年受试者工作特征曲线下面积相似（分别为 0.772、0.818、0.739 和 0.780）。
高风险 MASH 患者和无 MASH 的 F2-F4 纤维化患者的 LRE 风险相似。使用 LSM≥10kPa 或 AGILE 3+>0.67 可能是识别值得纳入临床试验的 MASLD 患者的准确选择。
