Evidence map›Paper›PMID 40637304›Full record

Observational studyEuropean journal of clinical investigation2025

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

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, TransplantLines Investigators

Registry-linked trialAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in European journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03272841 (TransplantLines), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03272841 unknown statusnot on this map

TransplantLines: the Transplantation Biobank

Typeobservational_patient_registrySponsorUniversity Medical Center GroningenRan2015 to 2021Enrolled3,000ConditionsSolid Organ Tranplant Recipients, 18+ Years
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Yakun LiDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID https://orcid.org/0009-0001-8717-6476
Mateo Chvatal-MedinaDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Maria Camila Trillos-AlmanzaDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Margery A ConnellyLabcorp, Morrisville, North Carolina, USA.
Han MoshageDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Stephan J L BakkerDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Vincent E de MeijerDepartment of Surgery, Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Hans BlokzijlDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Robin P F DullaartDepartment of Internal Medicine, Division of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID https://orcid.org/0000-0003-4520-1239
TransplantLines Investigators

Funding

Astellas BVChiesi Pharmaceuticals BV PA-SP/PRJ-2020-9136Dutch Ministry of Economic Affairs and Climate Policy PPP-2019-032Dutch Ministry of Economic Affairs and Climate Policy PPP-2022-015NWO/TTW 14939
6 · The paper itself

Abstract

BACKGROUND AND

aimsBranched-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.

methodsPlasma 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.

resultsTotal 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).

conclusionsTotal 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.

Indexed as

Amino Acids, Branched-ChainDiabetes Mellitus, Type 2Liver CirrhosisLiver TransplantationAdultAgedFemaleHumansKaplan-Meier EstimateMaleMiddle AgedProportional Hazards ModelsAmino Acids, Branched-Chainbranched‐chain amino acidsliver cirrhosisliver transplantationmortalitytype 2 diabetes

Identifiers

PMID40637304
PMCPMC12621290

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.