医学
列线图
肝硬化
内科学
队列
危险系数
曲线下面积
肝细胞癌
接收机工作特性
弗雷明翰风险评分
代谢组学
胃肠病学
肿瘤科
置信区间
生物信息学
生物
疾病
作者
Chengnan Guo,Zhenqiu Liu,Fan Hong,Haili Wang,Xin Zhang,Shanshan Zhao,Yi Li,Xinyu Han,Tianye Wang,Xingdong Chen,Tiejun Zhang
标识
DOI:10.1097/hep.0000000000000879
摘要
The liver cirrhosis complications occur after long asymptomatic stages of progressive fibrosis and are generally diagnosed late. We aimed to develop a plasma metabolomic-based score tool to predict these events.We enrolled 64,005 UK biobank participants with metabolomic profile. Participants were randomly divided into the training (n=43,734) and validation cohorts (n=20,271). Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with hepatocellular carcinoma. Interpretable machine learning framework was applied to learn the metabolomic states extracted from 168 circulating metabolites in the training cohort. An integrated nomogram was developed and compared to conventional and genetic risk scores. We created three groups: low-risk, middle-risk, and high-risk through selected cut-offs of the nomogram. The predictive performance was validated through area under time-dependent receiver operating characteristic curve (time-dependent AUC), calibration curves, and decision curve analysis. The metabolomic state model could accurately predict 10-year risk of liver cirrhosis complications in the training cohort (time-dependent AUC 0.84 [95% CI 0.82-0.86]), and outperform the fibrosis-4 index (time-dependent AUC difference 0.06 [0.03-0.10]) and polygenic risk score (0.25 [0.21-0.29]). The nomogram, integrating metabolomic state, aspartate aminotransferase, platelet count, waist/hip ratio, and smoking status, showed a time-dependent AUC of 0.930 at 3 years, 0.889 at 5 years, and 0.861 at 10 years in the validation cohort, respectively. The hazard ratio in the high-risk group was 43.58 (95% CI 27.08-70.12) compared with the low-risk group.We developed a metabolomic state-integrated nomogram, which enables risk stratification and personalized administration of liver-related events.
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