Branched-chain amino acids and all-cause mortality in patients with liver cirrhosis, and the onset of diabetes in liver transplant recipients.

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation Pub Date : 2025-07-10 DOI:10.1111/eci.70096

Yakun Li, Mateo Chvatal-Medina, Maria Camila Trillos-Almanza, Margery A Connelly, Han Moshage, Stephan J L Bakker, Vincent E de Meijer, Hans Blokzijl, Robin P F Dullaart

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Abstract

Background and aims: Branched-chain amino acids (BCAA) have gained increasing recognition for their role in liver disease. This study investigated plasma BCAA alterations in patients with cirrhosis and liver transplant recipients (LTRs) and examined their associations with all-cause mortality and new-onset type 2 diabetes in LTRs.

Methods: Plasma BCAA concentrations were measured using nuclear magnetic resonance spectroscopy in 129 patients with cirrhosis and 367 LTRs from the TransplantLines cohort study (NCT03272841), and compared with 4834 participants from the population-based PREVEND cohort. Kaplan-Meier survival analysis and Cox regression analysis were performed.

Results: Total BCAA levels were significantly lower in patients with cirrhosis and LTRs than in PREVEND participants (p < .001). While total BCAA levels increased post-transplant, they remained lower than those in PREVEND (p < .001). The highest total BCAA tertile was associated with better survival versus the lowest BCAA tertile in patients with cirrhosis (log-rank p = .002). In Cox regression analysis adjusted for relevant co-variates, higher total BCAA levels were also associated with reduced mortality in patients with cirrhosis (HR .19 [95% CI: .04-.86], p = .031). In LTRs, the highest total BCAA tertile conferred a higher probability of new-onset diabetes (log-rank p = .004) but was not linked to mortality (log-rank p = .65). After adjusting for age, sex, and immunosuppressant use, the highest tertile of total BCAA levels remained independently associated with new-onset diabetes in LTRs (HR 1.42 [95% CI: 1.10-1.82], p = .006).

Conclusions: Total BCAA levels increase after liver transplantation. In patients with cirrhosis, higher total BCAA levels are associated with reduced all-cause mortality. Although this association is not evident in LTRs, higher total BCAA levels are strongly linked to an increased risk of new-onset type 2 diabetes, warranting further investigation.

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肝硬化患者的支链氨基酸和全因死亡率，以及肝移植受者糖尿病的发病。

背景和目的：支链氨基酸（BCAA）在肝脏疾病中的作用越来越受到重视。本研究调查了肝硬化和肝移植受者（LTRs）的血浆BCAA改变，并研究了它们与LTRs全因死亡率和新发2型糖尿病的关系。方法：使用核磁共振波谱法测量来自plantlines队列研究（NCT03272841）的129名肝硬化患者和367名ltr患者的血浆BCAA浓度，并与来自基于人群的PREVEND队列的4834名参与者进行比较。Kaplan-Meier生存分析和Cox回归分析。结果：肝硬化和ltr患者的总BCAA水平明显低于prevention参与者(p结论：肝移植后总BCAA水平升高。在肝硬化患者中，较高的总BCAA水平与降低的全因死亡率相关。尽管这种关联在ltr中并不明显，但较高的总BCAA水平与新发2型糖尿病风险增加密切相关，值得进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Clinical Investigation 医学-医学：内科

CiteScore

9.50

自引率

3.60%

发文量

192

审稿时长

1 months

期刊介绍： EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.