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Background <p>Acute-on-chronic liver failure (ACLF) exhibits high mortality and heterogeneity, demanding precise risk stratification. We aimed to identify metabolic subtypes and explore their association with prognosis and real-world artificial liver support (ALS) responsiveness.</p> Methods <p>This prospective, multicenter, observational cohort study enrolled 142 ACLF patients. Serum was collected at baseline, prior to ALS initiation. Patients were subtyped via metabolomics clustering. ALS exposure was analyzed using inverse probability of treatment weighting (IPTW) and Cox models to test for heterogeneity of treatment effect.</p> Results <p>Two subtypes were identified (Cluster 1/2). Cluster 2 showed significantly higher 90&#xa0;day mortality (<i>p</i> = 0.032) and severe amino acid metabolic reprogramming, particularly in branched-chain amino acid and glutamine pathways. Exploratory analysis suggested a differential association between ALS and survival across subtypes (interaction <i>p</i> = 0.12). ALS showed a weaker survival association in Cluster 2 after IPTW adjustment.</p> Conclusion <p>ACLF patients possess distinct amino acid-based metabolic subtypes that are potent prognostic indicators. Baseline metabolic profiling can serve as a stratification tool to identify patients who may derive the greatest clinical benefit from ALS therapy, guiding personalized treatment strategies.</p>

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Distinct amino acid metabolic subtypes predict prognosis and stratify treatment response in acute-on-chronic liver failure: a multicenter prospective study

  • 期刊论文

  • 发表日期：

    2026年3月30日

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  • Haocheng Zheng,
  • Simiao Yu,
  • Ting Zhou,
  • Shuangnan Fu,
  • Jingjing Zhang,
  • Ning Zhang,
  • Yijiang Liu,
  • Yanyang Huang,
  • Zhaoyun He,
  • Jin Zhang,
  • Pengcheng Liu,
  • Man Gong,
  • Chao Zhou

摘要

Background

Acute-on-chronic liver failure (ACLF) exhibits high mortality and heterogeneity, demanding precise risk stratification. We aimed to identify metabolic subtypes and explore their association with prognosis and real-world artificial liver support (ALS) responsiveness.

Methods

This prospective, multicenter, observational cohort study enrolled 142 ACLF patients. Serum was collected at baseline, prior to ALS initiation. Patients were subtyped via metabolomics clustering. ALS exposure was analyzed using inverse probability of treatment weighting (IPTW) and Cox models to test for heterogeneity of treatment effect.

Results

Two subtypes were identified (Cluster 1/2). Cluster 2 showed significantly higher 90 day mortality (p = 0.032) and severe amino acid metabolic reprogramming, particularly in branched-chain amino acid and glutamine pathways. Exploratory analysis suggested a differential association between ALS and survival across subtypes (interaction p = 0.12). ALS showed a weaker survival association in Cluster 2 after IPTW adjustment.

Conclusion

ACLF patients possess distinct amino acid-based metabolic subtypes that are potent prognostic indicators. Baseline metabolic profiling can serve as a stratification tool to identify patients who may derive the greatest clinical benefit from ALS therapy, guiding personalized treatment strategies.