西班牙巴塞罗那临床医院Pere Ginès团队对普通人群中长期肝脏相关预后风险评分进行了开发、验证和预后评估。2023年8月9日出版的《柳叶刀》杂志发表了这项成果。

肝硬化是全世界死亡的主要原因。肝硬化是在长期无症状的纤维化进展后发展起来的，诊断经常发生在晚期，此时会出现严重并发症或癌症。很少有可靠的工具可以及时识别有肝硬化风险的个体，以便进行早期干预。该研究旨在开发一种新的评分来识别未来肝脏相关结果的风险个体。

研究组从一个国际前瞻性队列中得出了LiverRisk评分，该队列由来自六个国家的普通人群中没有已知肝病的个体组成，他们通过瞬态弹性成像进行了肝纤维化评估。评分包括年龄、性别和六个标准实验室变量。研究组根据LiverRisk评分的选定截止值（6、10和15）创建了四组：最小风险组、低风险组、中等风险组和高风险组。该模型的判别准确性和校准在来自普通人群的两个前瞻性队列中进行了外部验证。此外还确定了该评分在预测无已知肝病参与者的肝脏相关结果中的预后价值，中位随访时间为12年（英国生物银行队列）。

研究组纳入了14726名参与者：6357名（43.2%）在衍生队列中，4370名（29.7%）在第一个外部验证队列中，3999名（27.2%）在第二个外部验证群组中。该评分准确预测了进展组和外部验证组的肝硬度，并优于传统的纤维化血清生物标志物，通过受试者操作特征曲线下面积（AUC；0.83）与纤维化-4指数（FIB-4；0.68，10kPa）进行测量。该评分在识别有肝脏相关死亡、肝脏相关住院和癌症风险的个体方面是有效的，从而允许对不同的肝脏相关结局风险组进行分层。与最低风险组相比，高危组肝脏相关死亡率的危险比为471，预测10年肝脏相关死亡率得分的总体AUC为0.90，FIB-4为0.84。

研究结果表明，基于简单参数的LiverRisk评分可预测普通人群的肝纤维化和肝脏相关结局的未来进展。该评分或允许根据肝脏风险对个体进行分层，从而指导预防性护理。

附：英文原文

Title: Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study

Author: Miquel Serra-Burriel, Adrià Juanola, Feliu Serra-Burriel, Maja Thiele, Isabel Graupera, Elisa Pose, Guillem Pera, Ivica Grgurevic, Lloren Caballeria, Salvatore Piano, Laurens van Kleef, Mathias Reichert, Dominique Roulot, Juan M Pericàs, Jrn M Schattenberg, Emmanuel A Tsochatztis, Indra Neil Guha, Montserrat Garcia-Retortillo, Rosario Hernández, Jordi Hoyo, Matilde Fuentes, Carmen Expósito, Alba Martínez, Patricia Such, Anita Madir, Snke Detlefsen, Marta Tonon, Andrea Martini, Ann T Ma, Judith Pich, Eva Bonfill, Marta Juan, Anna Soria, Marta Carol, Jordi Gratacós-Ginès, Rosa M Morillas, Pere Toran, J M Navarrete, Antoni Torrejón, Céline Fournier, Anne Llorca, Anita Arslanow, Harry J de Koning, Fernando Cucchietti, Michael Manns, Phillip N Newsome, Rubén Hernáez, Alina Allen, Paolo Angeli, Robert J de Knegt, Tom H Karlsen, Peter Galle, Vincent Wai-Sun Wong, Núria Fabrellas, Laurent Castera, Aleksander Krag, Frank Lammert, Patrick S Kamath, Pere Ginès, Marifé Alvarez, Peter Andersen

Issue&Volume: 2023-08-09

Abstract:

Background

Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes.

Methods

We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort).

Findings

We included 14726 participants: 6357 (43·2%) in the derivation cohort, 4370 (29·7%) in the first external validation cohort, and 3999 (27·2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC; 0·83 [95% CI [0·78–0·89]) versus the fibrosis-4 index (FIB-4; 0·68 [0·61–0·75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI 347–641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liver-related mortality was 0·90 (0·88–0·91) versus 0.84 (0·82–0·86) for FIB-4.

Interpretation

The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care.

DOI: 10.1016/S0140-6736(23)01174-1

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01174-1/fulltext