{"doi":"10.1111/eci.70096","title":"Branched‐chain amino acids and all‐cause mortality in patients with liver cirrhosis, and the onset of diabetes in liver transplant recipients","abstract":"Abstract\n \n Background and Aims\n \n Branched‐chain amino acids (\n BCAA\n ) have gained increasing recognition for their role in liver disease. This study investigated plasma\n BCAA\n alterations in patients with cirrhosis and liver transplant recipients (\n LTRs\n ) and examined their associations with all‐cause mortality and new‐onset type 2 diabetes in\n LTRs\n .\n \n \n \n Methods\n \n Plasma\n BCAA\n concentrations were measured using nuclear magnetic resonance spectroscopy in 129 patients with cirrhosis and 367\n LTRs\n from the\n TransplantLines\n cohort study (\n NCT03272841\n ), and compared with 4834 participants from the population‐based\n PREVEND\n cohort. Kaplan–Meier survival analysis and Cox regression analysis were performed.\n \n \n \n Results\n \n Total\n BCAA\n levels were significantly lower in patients with cirrhosis and\n LTRs\n than in\n PREVEND\n participants (\n p\n < .001). While total\n BCAA\n levels increased post‐transplant, they remained lower than those in\n PREVEND\n (\n p\n < .001). The highest total\n BCAA\n tertile was associated with better survival versus the lowest\n BCAA\n tertile in patients with cirrhosis (log‐rank\n p\n = .002). In Cox regression analysis adjusted for relevant co‐variates, higher total\n BCAA\n levels were also associated with reduced mortality in patients with cirrhosis (\n HR\n .19 [95%\n CI\n : .04–.86],\n p\n = .031). In\n LTRs\n , the highest total\n BCAA\n tertile conferred a higher probability of new‐onset diabetes (log‐rank\n p\n = .004) but was not linked to mortality (log‐rank\n p\n = .65). After adjusting for age, sex, and immunosuppressant use, the highest tertile of total\n BCAA\n levels remained independently associated with new‐onset diabetes in\n LTRs\n (\n HR\n 1.42 [95%\n CI\n : 1.10–1.82],\n p\n = .006).\n \n \n \n Conclusions\n \n Total\n BCAA\n levels increase after liver transplantation. In patients with cirrhosis, higher total\n BCAA\n levels are associated with reduced all‐cause mortality. Although this association is not evident in\n LTRs\n , higher total\n BCAA\n levels are strongly linked to an increased risk of new‐onset type 2 diabetes, warranting further investigation.\n \n ","journal":"European Journal of Clinical Investigation","year":2025,"id":626977,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1622239,"name":"Mateo Chvatal‐Medina","orcid":null,"position":1,"is_corresponding":false},{"id":1622240,"name":"Maria Camila Trillos‐Almanza","orcid":null,"position":2,"is_corresponding":false},{"id":293941,"name":"Margery A. Connelly","orcid":"0000-0002-3917-592X","position":3,"is_corresponding":false},{"id":1622241,"name":"Han Moshage","orcid":null,"position":4,"is_corresponding":false},{"id":21853,"name":"Stephan J. L. Bakker","orcid":"0000-0003-3356-6791","position":5,"is_corresponding":false},{"id":1047831,"name":"Vincent E. de Meijer","orcid":"0000-0002-7900-5917","position":6,"is_corresponding":false},{"id":1622242,"name":"Hans Blokzijl","orcid":null,"position":7,"is_corresponding":false},{"id":899745,"name":"Robin P.F. Dullaart","orcid":"0000-0003-4520-1239","position":8,"is_corresponding":false},{"id":1622238,"name":"Yakun Li","orcid":"0009-0001-8717-6476","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Branched‐chain amino acids and all‐cause mortality in patients with liver cirrhosis, and the onset of diabetes in liver transplant recipients","abstract":"Abstract\n \n Background and Aims\n \n Branched‐chain amino acids (\n BCAA\n ) have gained increasing recognition for their role in liver disease. This study investigated plasma\n BCAA\n alterations in patients with cirrhosis and liver transplant recipients (\n LTRs\n ) and examined their associations with all‐cause mortality and new‐onset type 2 diabetes in\n LTRs\n .\n \n \n \n Methods\n \n Plasma\n BCAA\n concentrations were measured using nuclear magnetic resonance spectroscopy in 129 patients with cirrhosis and 367\n LTRs\n from the\n TransplantLines\n cohort study (\n NCT03272841\n ), and compared with 4834 participants from the population‐based\n PREVEND\n cohort. Kaplan–Meier survival analysis and Cox regression analysis were performed.\n \n \n \n Results\n \n Total\n BCAA\n levels were significantly lower in patients with cirrhosis and\n LTRs\n than in\n PREVEND\n participants (\n p\n < .001). While total\n BCAA\n levels increased post‐transplant, they remained lower than those in\n PREVEND\n (\n p\n < .001). The highest total\n BCAA\n tertile was associated with better survival versus the lowest\n BCAA\n tertile in patients with cirrhosis (log‐rank\n p\n = .002). In Cox regression analysis adjusted for relevant co‐variates, higher total\n BCAA\n levels were also associated with reduced mortality in patients with cirrhosis (\n HR\n .19 [95%\n CI\n : .04–.86],\n p\n = .031). In\n LTRs\n , the highest total\n BCAA\n tertile conferred a higher probability of new‐onset diabetes (log‐rank\n p\n = .004) but was not linked to mortality (log‐rank\n p\n = .65). After adjusting for age, sex, and immunosuppressant use, the highest tertile of total\n BCAA\n levels remained independently associated with new‐onset diabetes in\n LTRs\n (\n HR\n 1.42 [95%\n CI\n : 1.10–1.82],\n p\n = .006).\n \n \n \n Conclusions\n \n Total\n BCAA\n levels increase after liver transplantation. In patients with cirrhosis, higher total\n BCAA\n levels are associated with reduced all‐cause mortality. Although this association is not evident in\n LTRs\n , higher total\n BCAA\n levels are strongly linked to an increased risk of new‐onset type 2 diabetes, warranting further investigation.\n \n ","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40637304","pmcid":"PMC12621290","openalex_id":"https://openalex.org/W4412156334","authors":[],"funders":[{"funder_name":"Toegepaste en Technische Wetenschappen, NWO","grant_id":"14939","title":null},{"funder_name":"Ministerie van Economische Zaken en Klimaat","grant_id":"PPP‐2019‐032","title":null},{"funder_name":"Ministerie van Economische Zaken en Klimaat","grant_id":"PPP‐2022‐015","title":null},{"funder_name":"Dutch Ministry of Economic Affairs and Climate Policy","grant_id":"PPP-2022-015","title":null},{"funder_name":"Chiesi Pharmaceuticals BV","grant_id":"PA-SP/PRJ-2020-9136","title":null},{"funder_name":"Dutch Ministry of Economic Affairs and Climate Policy","grant_id":"PPP-2019-032","title":null},{"funder_name":"Astellas BV","grant_id":"","title":null},{"funder_name":"Astellas BV","grant_id":"","title":null}],"total_grants":8,"fwci":2.4378,"citation_percentile":0.89195497,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/eci.70096","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/eci.70096","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/eci.70096","host_type":"publisher"},{"url":"https://doi.org/10.1111/eci.70096","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40637304","host_type":"repository"},{"url":"https://research.rug.nl/en/publications/b61c7d3f-21bd-444c-8477-d8de756945ad","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12621290","host_type":"repository"},{"url":"https://hdl.handle.net/11370/b61c7d3f-21bd-444c-8477-d8de756945ad","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12621290","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12621290?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Metabolomics and Mass Spectrometry Studies","Metabolism and Genetic Disorders","Advanced MRI Techniques and Applications","Adult","Aged","Female","Humans","Male","Middle Aged","Amino Acids, Branched-Chain","Diabetes Mellitus, Type 2","Kaplan-Meier Estimate","Liver Cirrhosis","Liver Transplantation","Proportional Hazards Models"],"mesh_terms":["Adult","Aged","Amino Acids, Branched-Chain","Diabetes Mellitus, Type 2","Female","Humans","Liver Cirrhosis","Male","Middle Aged","Proportional Hazards Models","Liver Transplantation","Kaplan-Meier Estimate"],"keywords":["Cirrhosis","Diabetes mellitus","Medicine","Internal medicine","Gastroenterology","Liver transplantation","Endocrinology","Transplantation","Mortality","Liver cirrhosis","Type 2 diabetes","Branched‐chain Amino Acids"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T15:51:52.150214Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}