Yip Terry Cheuk-Fung, Lee Hye Won, Lin Huapeng, Tsochatzis Emmanuel, Petta Salvatore, Bugianesi Elisabetta, Yoneda Masato, Zheng Ming-Hua, Hagström Hannes, Boursier Jérôme, Calleja José Luis, Goh George Boon-Bee, Chan Wah-Kheong, Gallego-Durán Rocio, Sanyal Arun J, de Lédinghen Victor, Newsome Philip N, Fan Jian-Gao, Castéra Laurent, Lai Michelle, Fournier-Poizat Céline, Wong Grace Lai-Hung, Pennisi Grazia, Armandi Angelo, Nakajima Atsushi, Liu Wen-Yue, Shang Ying, de Saint-Loup Marc, Llop Elba, Teh Kevin Kim Jun, Lara-Romero Carmen, Asgharpour Amon, Mahgoub Sara, Chan Mandy Sau-Wai, Canivet Clemence M, Romero-Gomez Manuel, Kim Seung Up, Wong Vincent Wai-Sun
Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
J Hepatol. 2025 Jan 23. doi: 10.1016/j.jhep.2025.01.014.
BACKGROUND & AIMS: Current guidelines recommend a two-step approach for risk stratification in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) involving Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) or similar second-line tests. This study aimed to examine the prognostic performance of this approach.
The VCTE-Prognosis study was a longitudinal study of patients with MASLD who had undergone VCTE examinations at 16 centres from the US, Europe and Asia with subsequent follow-up for clinical events. The primary endpoint was incident liver-related events (LREs), defined as hepatic decompensation and/or hepatocellular carcinoma.
Of 12,950 patients (mean age 52 years, 41% female, 12.1% LSM >12 kPa), baseline FIB-4, at cut-offs of 1.3 (or 2.0 for age ≥65) and 2.67, classified 66.3% as low-risk and 9.8% as high-risk, leaving 23.9% in the intermediate-risk zone. After classifying intermediate FIB-4 patients as low-risk if LSM was <8.0 kPa and high-risk if LSM was >12.0 kPa, 81.5%, 4.6%, and 13.9% of the full cohort were classified as low-, intermediate-, and high-risk, respectively. At a median (IQR) follow-up of 47 (23-72) months, 248 (1.9%) patients developed LREs. The 5-year cumulative incidence of LREs was 0.5%, 1.0% and 10.8% in the low-, intermediate- and high-risk groups, respectively. Replacing LSM with Agile 3+, Agile 4, and FAST did not reduce the intermediate-risk zone or improve event prediction. Classifying intermediate FIB-4 patients by LSM <10 kPa (low-risk) and >15 kPa (high-risk) reduced the intermediate-risk zone while maintaining predictive performance.
The non-invasive two-step approach of FIB-4 followed by LSM is effective in classifying patients at different risks of LREs.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is emerging as one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide, but only a minority of patients will develop these complications. Therefore, it is necessary to use non-invasive tests instead of liver biopsy for risk stratification. Additionally, as most patients with MASLD are seen in primary care instead of specialist settings, cost and availability of the tests should be taken into consideration. In this multicentre study, the use of the Fibrosis-4 index followed by liver stiffness measurement by vibration-controlled transient elastography effectively identified patients who would later develop liver-related events. The results support current recommendations by various regional guidelines on a clinical care pathway based on non-invasive tests to diagnose advanced liver fibrosis.
当前指南推荐采用两步法对代谢功能障碍相关脂肪性肝病（MASLD）患者进行风险分层，第一步使用纤维化-4指数（FIB-4），第二步通过振动控制瞬时弹性成像（VCTE）或类似的二线检查进行肝脏硬度测量（LSM）。本研究旨在检验该方法的预后性能。
VCTE-预后研究是一项对MASLD患者的纵向研究，这些患者在美国、欧洲和亚洲的16个中心接受了VCTE检查，并随后对临床事件进行随访。主要终点是发生肝脏相关事件（LREs），定义为肝失代偿和/或肝细胞癌。
在12950例患者中（平均年龄52岁，41%为女性，12.1%的LSM>12 kPa），FIB-4在截断值为1.3（年龄≥65岁时为2.0）和2.67时，将66.3%的患者分类为低风险，9.8%为高风险，23.9%处于中风险区。如果LSM<8.0 kPa，将FIB-4处于中间范围的患者分类为低风险；如果LSM >12.0 kPa，则分类为高风险，全队列中分别有81.5%、4.6%和13.9%的患者被分类为低、中、高风险。在中位（IQR）随访47（23 - 72）个月时，248例（1.9%）患者发生了LREs。低、中、高风险组LREs的5年累积发生率分别为0.5%、1.0%和10.8%。用Agile 3+、Agile 4和FAST替代LSM并没有减少中风险区或改善事件预测。将FIB-4处于中间范围的患者按LSM<10 kPa（低风险）和>15 kPa（高风险）分类可减少中风险区，同时保持预测性能。
FIB-4联合LSM的非侵入性两步法可有效对具有不同LREs风险的患者进行分类。
代谢功能障碍相关脂肪性肝病（MASLD）正在成为全球肝硬化和肝细胞癌的主要原因之一，但只有少数患者会发生这些并发症。因此，有必要使用非侵入性检查而非肝活检进行风险分层。此外，由于大多数MASLD患者是在初级保健机构而非专科机构就诊，应考虑检查的成本和可及性。在这项多中心研究中，使用纤维化-4指数，随后通过振动控制瞬时弹性成像进行肝脏硬度测量，有效地识别出了后来会发生肝脏相关事件的患者。结果支持了各地区指南关于基于非侵入性检查诊断晚期肝纤维化的临床护理路径的当前建议。
