Åberg Fredrik, Männistö Ville, Asteljoki Juho, Salomaa Veikko, Jula Antti, Lundqvist Annamari, Männistö Satu, Perola Markus, Luukkonen Panu K
Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Department of Medicine, University of Eastern Finland, Kuopio, Finland.
Hepatol Commun. 2025 Mar 21;9(4). doi: 10.1097/HC9.0000000000000679. eCollection 2025 Apr 1.
Liver fibrosis screening is recommended in at-risk groups, but a clear definition of "at risk" for entry criteria is lacking. We analyzed different combinations of established risk factors to define specific screening entry criteria with a prespecified sensitivity requirement.
Data regarding individuals aged 40-70 years from Finnish health-examination surveys (FINRISK 2002-2012 and Health 2000, n=15,057) and the UK Biobank (n=454,990) were linked with healthcare registries for liver cirrhosis-related events (LREs; liver-related hospitalizations, cancer, or death). The predictive performance of 1919 combinations of risk factors, including alcohol consumption, metabolic disturbances, abnormal liver function tests, and Chronic Liver Disease risk score, was assessed for 10-year LRE risk requiring a minimum 90% sensitivity. Validations were performed using liver stiffness measurement (LSM) >12 kPa in the NHANES 2017-2020 sample (n=3367).
Optimal entry criteria for predicting 10-year LRE risk with >90% sensitivity included any one of: hazardous alcohol use, severe obesity, metabolic syndrome, an AST-to-ALT ratio >0.8 with elevated ALT, and an intermediate-to-high Chronic Liver Disease risk score. The sensitivity and specificity for this strategy were 91% and 51% for LREs, respectively, in the Finnish cohort, and 91% and 41% for LSM >12 kPa in the US sample. In the US sample, applying these entry criteria followed by fibrosis-4 ≥1.3 for predicting LSM >12 kPa reduced the sensitivity to 45% (specificity: 85%), which was attributed to the suboptimal sensitivity of fibrosis-4.
This study identifies an inexpensive risk factor-based strategy with >90% sensitivity for predicting LRE and LSM >12 kPa, which is practical and scalable for targeted liver fibrosis screening to improve population outcomes. However, a more sensitive first-line noninvasive fibrosis test is needed.
建议对高危人群进行肝纤维化筛查，但缺乏关于纳入标准中“高危”的明确定义。我们分析了既定风险因素的不同组合，以确定具有预先设定敏感性要求的特定筛查纳入标准。
来自芬兰健康检查调查（FINRISK 2002 - 2012和Health 2000，n = 15,057）以及英国生物银行（n = 454,990）的40 - 70岁个体的数据与肝硬化相关事件（LREs；肝脏相关住院、癌症或死亡）的医疗登记数据相链接。评估了1919种风险因素组合的预测性能，这些组合包括饮酒、代谢紊乱、肝功能检查异常以及慢性肝病风险评分，用于预测10年LRE风险，要求最低敏感性为90%。在2017 - 2020年美国国家健康与营养检查调查（NHANES）样本（n = 3367）中，使用肝脏硬度测量（LSM）>12 kPa进行验证。
预测10年LRE风险且敏感性>90%的最佳纳入标准包括以下任何一项：有害饮酒、重度肥胖、代谢综合征、AST与ALT比值>0.8且ALT升高，以及中高慢性肝病风险评分。在芬兰队列中，该策略对LREs的敏感性和特异性分别为91%和51%，在美国样本中，对于LSM >12 kPa，敏感性和特异性分别为91%和41%。在美国样本中，应用这些纳入标准后再加上纤维化-4≥1.3来预测LSM >12 kPa，敏感性降至45%（特异性：85%），这归因于纤维化-4的敏感性欠佳。
本研究确定了一种基于风险因素的低成本策略，对预测LRE和LSM >12 kPa具有>90%的敏感性，该策略对于有针对性的肝纤维化筛查是实用且可扩展的，有助于改善人群健康结局。然而，需要一种更敏感的一线非侵入性纤维化检测方法。
