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肝纤维化检测的预后持久性以及通过联合检测提高死亡率预测性能

Prognostic durability of liver fibrosis tests and improvement in predictive performance for mortality by combining tests.

作者信息

Bertrais Sandrine, Boursier Jérôme, Ducancelle Alexandra, Oberti Frédéric, Fouchard-Hubert Isabelle, Moal Valérie, Calès Paul

机构信息

HIFIH research unit, UBL University, Angers, France.

Department of Hepato-Gastroenterology, University Hospital, Angers, France.

出版信息

J Gastroenterol Hepatol. 2017 Jun;32(6):1240-1249. doi: 10.1111/jgh.13668.

Abstract

BACKGROUND AND AIM

There is currently no recommended time interval between noninvasive fibrosis measurements for monitoring chronic liver diseases. We determined how long a single liver fibrosis evaluation may accurately predict mortality, and assessed whether combining tests improves prognostic performance.

METHODS

We included 1559 patients with chronic liver disease and available baseline liver stiffness measurement (LSM) by Fibroscan, aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Hepascore, and FibroMeter .

RESULTS

Median follow-up was 2.8 years during which 262 (16.8%) patients died, with 115 liver-related deaths. All fibrosis tests were able to predict mortality, although APRI (and FIB-4 for liver-related mortality) showed lower overall discriminative ability than the other tests (differences in Harrell's C-index: P < 0.050). According to time-dependent AUROCs, the time period with optimal predictive performance was 2-3 years in patients with no/mild fibrosis, 1 year in patients with significant fibrosis, and <6 months in cirrhotic patients even in those with a model of end-stage liver disease (MELD) score <15. Patients were then randomly split in training/testing sets. In the training set, blood tests and LSM were independent predictors of all-cause mortality. The best-fit multivariate model included age, sex, LSM, and FibroMeter with C-index = 0.834 (95% confidence interval, 0.803-0.862). The prognostic model for liver-related mortality included the same covariates with C-index = 0.868 (0.831-0.902). In the testing set, the multivariate models had higher prognostic accuracy than FibroMeter or LSM alone for all-cause mortality and FibroMeter alone for liver-related mortality.

CONCLUSIONS

The prognostic durability of a single baseline fibrosis evaluation depends on the liver fibrosis level. Combining LSM with a blood fibrosis test improves mortality risk assessment.

摘要

背景与目的

目前尚无关于监测慢性肝病的非侵入性纤维化测量之间推荐的时间间隔。我们确定了单次肝纤维化评估能够准确预测死亡率的时长,并评估了联合检测是否能改善预后性能。

方法

我们纳入了1559例慢性肝病患者,这些患者可获得通过Fibroscan进行的基线肝脏硬度测量(LSM)、天冬氨酸氨基转移酶与血小板比值指数(APRI)、FIB-4、Hepascore和FibroMeter。

结果

中位随访时间为2.8年,在此期间262例(16.8%)患者死亡,其中115例为肝脏相关死亡。所有纤维化检测均能够预测死亡率,尽管APRI(以及用于肝脏相关死亡率的FIB-4)的总体鉴别能力低于其他检测(Harrell C指数差异:P<0.050)。根据时间依赖性受试者工作特征曲线下面积(AUROCs),预测性能最佳的时间段在无/轻度纤维化患者中为2 - 3年,在显著纤维化患者中为1年,在肝硬化患者中为<6个月,即使是终末期肝病模型(MELD)评分<15的患者。然后将患者随机分为训练/测试组。在训练组中,血液检测和LSM是全因死亡率的独立预测因素。最佳拟合多变量模型包括年龄、性别、LSM和FibroMeter,C指数 = 0.834(95%置信区间,0.803 - 0.862)。肝脏相关死亡率的预后模型包括相同的协变量,C指数 = 0.868(0.831 - 0.902)。在测试组中,多变量模型对于全因死亡率的预后准确性高于单独的FibroMeter或LSM,对于肝脏相关死亡率的预后准确性高于单独的FibroMeter。

结论

单次基线纤维化评估的预后持久性取决于肝纤维化水平。将LSM与血液纤维化检测相结合可改善死亡风险评估。

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