Kaya Eda, Aksoy Sinem, Oruc Nazlican, Tasdemir Cagla, Cengiz Beyza Irem, Keklikkiran Caglayan, Yilmaz Yusuf
Department of Medicine, University Hospital Knappschaft Kliniken Bochum, Ruhr University Bochum, Bochum, Germany.
The Global NASH Council, Washington DC, USA.
Hepatol Forum. 2025 Jul 7;6(3):111-115. doi: 10.14744/hf.2025.2025.0050. eCollection 2025.
Resmetirom received conditional Food and Drug Administration (FDA) approval in 2024 for metabolic dysfunction-associated steatotic liver disease (MASLD) based on its promising liver-targeted therapy. Clinical trials required a histological diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) with F2-F3 fibrosis, excluding cirrhosis, while real-world prescribing relies on non-invasive tests (NITs). This study evaluates their efficacy in identifying the target population within a biopsy-proven Turkish MASLD cohort.
We analyzed 266 patients with biopsy-proven MASLD from the Turkish NAFLD Biobank. Inclusion required AST >17 U/L (females) or >20 U/L (males), and CAP ≥280 dB/m. Eligibility was defined by liver stiffness measurement (LSM) of 10-19.9 kPa (excluding cirrhosis or low platelet count) or a FAST score ≥0.67.
Among the study population, 130 patients (48.9%) had histologically confirmed MASH with F2-F3 fibrosis. Based on LSM criteria applied to histologically eligible patients, 81 patients (62.3%) were underdiagnosed, compared to 95 patients (73.1%) when using the FAST score. Additionally, among patients who corresponded to NIT, 34 patients (41.0%) were overprescribed using LSM, while 23 patients (39.7%) were overprescribed using the FAST score. The kappa value as a measure of agreement showed poor compatibility for both LSM and FAST with liver biopsy (0.128 and 0.101, respectively). When treatment decisions were guided by either of the NITs, 44 patients (44.0%) received unnecessary prescriptions, and 74 patients (44.6%) had missed diagnoses.
The NITs defined for identifying the target population for resmetirom demonstrated poor performance in accurately detecting or excluding eligible patients. Therefore, performing a liver biopsy before starting resmetirom treatment will prevent unnecessary increases in cost and significantly reduce the economic burden of the treatment.
Fibrosis; MASLD; MASH; non-invasive test; resmetirom.
基于其颇具前景的肝脏靶向治疗，瑞美替隆于2024年获得美国食品药品监督管理局（FDA）对代谢功能障碍相关脂肪性肝病（MASLD）的有条件批准。临床试验要求对代谢功能障碍相关脂肪性肝炎（MASH）伴F2 - F3纤维化（不包括肝硬化）进行组织学诊断，而实际临床处方则依赖于非侵入性检测（NITs）。本研究评估了它们在经活检证实的土耳其MASLD队列中识别目标人群的有效性。
我们分析了来自土耳其非酒精性脂肪性肝病生物样本库的266例经活检证实为MASLD的患者。纳入标准要求女性天门冬氨酸氨基转移酶（AST）>17 U/L或男性>20 U/L，且受控衰减参数（CAP）≥280 dB/m。符合条件的定义为肝脏硬度测量（LSM）为10 - 19.9 kPa（不包括肝硬化或血小板计数低的情况）或脂肪酸结合蛋白（FAST）评分≥0.67。
在研究人群中，130例患者（48.9%）经组织学证实为伴有F2 - F3纤维化的MASH。基于应用于组织学符合条件患者的LSM标准，81例患者（62.3%）被漏诊，而使用FAST评分时为95例患者（73.1%）。此外，在符合NIT的患者中，34例患者（41.0%）使用LSM时被过度处方，而23例患者（39.7%）使用FAST评分时被过度处方。作为一致性度量的kappa值显示LSM和FAST与肝活检的兼容性均较差（分别为0.128和0.101）。当治疗决策由任何一种NIT指导时，44例患者（44.0%）接受了不必要的处方，74例患者（44.6%）被漏诊。
为识别瑞美替隆目标人群所定义的NITs在准确检测或排除符合条件的患者方面表现不佳。因此，在开始瑞美替隆治疗前进行肝活检将避免不必要的成本增加，并显著减轻治疗的经济负担。
纤维化；MASLD；MASH；非侵入性检测；瑞美替隆
