A metabolome-derived score predicts metabolic dysfunction-associated steatohepatitis and mortality from liver disease

被引:0
作者
Huang, Qingxia [3 ]
Qadri, Sami F. [4 ,5 ]
Bian, Hua [1 ,2 ]
Yi, Xiaoxuan [3 ]
Lin, Chenhao [6 ]
Yang, Xinyu [1 ,2 ]
Zhu, Xiaopeng [1 ,2 ]
Lin, Huandong [1 ,2 ]
Yan, Hongmei [1 ,2 ]
Chang, Xinxia [1 ,2 ]
Sun, Xiaoyang [1 ,2 ]
Ma, Shuai [1 ,2 ]
Wu, Qi [1 ,2 ]
Zeng, Hailuan [1 ,2 ]
Hu, Xiqi [7 ]
Zheng, Yan
Yki-Jarvinen, Hannele [4 ,5 ]
Gao, Xin [1 ,2 ]
Tang, Huiru [1 ,3 ]
Xia, Mingfeng [1 ,2 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Dept Endocrinol & Metab, Shanghai, Peoples R China
[2] Fudan Univ, Fudan Inst Metab Dis, Shanghai, Peoples R China
[3] Fudan Univ, Zhongshan Hosp, Zhangjiang Fudan Int Innovat Ctr, State Key Lab Genet Engn,Sch Life Sci,Human Phenom, Shanghai 200438, Peoples R China
[4] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland
[5] Minerva Fdn, Inst Med Res, Helsinki, Finland
[6] Fudan Univ, Human Phenome Inst, Sch Life Sci, State Key Lab Genet Engn, Shanghai, Peoples R China
[7] Fudan Univ, Med Coll, Dept Pathol, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
proven MASH; MASLD-related death; metabolic dysfunction-associated steatohepatitis; metabolomics; machine learning; prediction score; mortality; NAFLD FIBROSIS SCORE; NONALCOHOLIC STEATOHEPATITIS; PROSPECTIVE DERIVATION; AMERICAN ASSOCIATION; CONSENSUS STATEMENT; INSULIN-RESISTANCE; DIAGNOSIS; VALIDATION; MANAGEMENT; EPIDEMIOLOGY;
D O I
10.1016/j.jhep.2024.10.015
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is associated with a >10-fold increase in liver-related mortality. However, biomarkers predicting both MASH and mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are missing. We developed a metabolome-derived prediction score for MASH and examined whether it predicts mortality in Chinese and European cohorts. Methods: The MASH prediction score was developed using a multi-step machine learning strategy, based on 44 clinical parameters and 250 serum metabolites measured by proton nuclear magnetic resonance in 311 Chinese adults undergoing a liver biopsy. External validation was conducted in a Finnish liver biopsy cohort (n = 305). We investigated associations of the score with all-cause and cause-specific mortality in the population-based Shanghai Changfeng study (n = 5,893) and the UK biobank (n = 111,673). Results: A total of 24 clinical parameters and 194 serum metabolites were significantly associated with MASH in the Chinese liver biopsy cohort. The final MASH score included BMI, aspartate aminotransferase, tyrosine, and the phospholipid-to-total lipid ratio in VLDL. The score identified patients with MASH with AUROCs of 0.87 (95% CI 0.83-0.91) and 0.81 (95% CI 0.75-0.88) in the Chinese and Finnish cohorts, with high negative predictive values. Participants with a high or intermediate risk of MASH based on the score had a markedly higher risk of MASLD-related mortality than those with a low risk in Chinese (hazard ratio 23.19; 95% CI 4.80-111.97) and European (hazard ratio 20.15; 95% CI 10.95-37.11) individuals after 7.2 and 12.6 years of follow-up, respectively. The MASH prediction score was superior to the Fibrosis-4 index and the NAFLD fibrosis score in predicting MASLDrelated mortality. Conclusion: The metabolome-derived MASH prediction score accurately predicts risk of MASH and MASLD-related mortality in both Chinese and European individuals.
引用
收藏
页码:781 / 793
页数:14
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