{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:04:05Z","timestamp":1789128245417,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by bile duct destruction, cholestasis, and fibrosis. Acylcarnitines are esters of carnitine responsible for the transport of long-chain fatty acids into mitochondria for \u03b2-oxidation, playing a crucial role in energy metabolism and lipid homeostasis. This study aimed to assess acylcarnitine and free fatty acid (FFA) profiles in PBC patients and their associations with fibrosis severity and inflammation. Methods: This cross-sectional study included 46 PBC patients and 32 healthy controls. Acylcarnitines and FFAs were quantified using liquid chromatography-tandem mass spectrometry (LC-MS\/MS) and enzymatic assays, respectively. Liver stiffness was measured by point shear wave elastography (ElastPQ), and fibrosis was assessed using APRI and FIB-4 scores. Inflammatory markers (IL-6, IL-1\u03b2) were also analyzed. Results: PBC patients had significantly higher levels of C18:1-acylcarnitine (median: 165.1 ng\/mL) compared with the controls (152.4 ng\/mL, p = 0.0036). Similarly, the FFA levels were markedly elevated in the PBC patients (median: 0.46 mM\/L) compared with the controls (0.26 mM\/L, p &lt; 0.0001). Patients with higher liver stiffness (ElastPQ &gt; 5.56 kPa) had significantly elevated C18:1-acylcarnitine (p = 0.0008) and FFA levels (p = 0.00098). Additionally, FFAs were significantly increased in patients with higher APRI and FIB-4 scores and were associated with elevated inflammatory markers (IL-6, IL-1\u03b2) and liver injury markers. Multivariate regression analysis confirmed C18:1-acylcarnitine (OR = 1.031, 95% CI: 1.007\u20131.057, p = 0.013) and FFAs (OR = 2.25 per 0.1 mM\/L increase, 95% CI: 1.20\u20134.22, p = 0.012) as independent predictors of fibrosis severity in PBC. Conclusions: C18:1-acylcarnitine and FFAs are significantly elevated in PBC and are strongly associated with fibrosis severity and inflammation. These findings suggest a link between lipid metabolism disturbances and PBC. Both metabolites may potentially serve as non-invasive biomarkers of fibrosis progression in PBC, warranting further investigation.<\/jats:p>","DOI":"10.3390\/nu17071097","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T04:58:38Z","timestamp":1742533118000},"page":"1097","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Acylcarnitine and Free Fatty Acid Profiles in Primary Biliary Cholangitis: Associations with Fibrosis and Inflammation"],"prefix":"10.3390","volume":"17","author":[{"given":"Magdalena","family":"Rogalska","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"B\u0142achnio-Zabielska","sequence":"additional","affiliation":[{"name":"Hygiene, Epidemiology and Metabolic Disorders Department, Medical University of Bialystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-5217","authenticated-orcid":false,"given":"Piotr","family":"Zabielski","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Medical University of Bialystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8448-3158","authenticated-orcid":false,"given":"Jacek Robert","family":"Janica","sequence":"additional","affiliation":[{"name":"Department of Pediatric Radiology, Medical University of Bialystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Roszczyc-Owsiejczuk","sequence":"additional","affiliation":[{"name":"Hygiene, Epidemiology and Metabolic Disorders Department, Medical University of Bialystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Pogodzi\u0144ska","sequence":"additional","affiliation":[{"name":"Hygiene, Epidemiology and Metabolic Disorders Department, Medical University of Bialystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Andrzejuk","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Medical University of Bialystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"D\u0105browski","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3394-1635","authenticated-orcid":false,"given":"Robert","family":"Flisiak","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Rogalski","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/S0140-6736(24)01303-5","article-title":"Primary biliary cholangitis","volume":"404","author":"Tanaka","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5706","DOI":"10.3748\/wjg.v11.i36.5706","article-title":"High concentration of antimitochondrial antibodies predicts progressive primary biliary cirrhosis","volume":"11","author":"Flisiak","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2017). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J. Hepatol., 67, 145\u2013172.","DOI":"10.1016\/j.jhep.2017.03.022"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.cld.2018.03.014","article-title":"Chronic Complications of Cholestasis: Evaluation and Management","volume":"22","author":"Assis","year":"2018","journal-title":"Clin. Liver Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Aseem, S.O., Hylemon, P.B., and Zhou, H. (2023). Bile Acids and Biliary Fibrosis. Cells, 12.","DOI":"10.3390\/cells12050792"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12986-018-0241-7","article-title":"Associations between fatty acid oxidation, hepatic mitochondrial function, and plasma acylcarnitine levels in mice","volume":"15","author":"Lindquist","year":"2018","journal-title":"Nutr. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1194\/jlr.D061721","article-title":"An LC-MS\/MS method to quantify acylcarnitine species including isomeric and odd-numbered forms in plasma and tissues","volume":"56","author":"Giesbertz","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ultras.2017.02.005","article-title":"The value of ElastPQ for the evaluation of liver stiffness in patients with B and C chronic hepatopathies","volume":"77","author":"Mare","year":"2017","journal-title":"Ultrasonics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1124\/pharmrev.121.000408","article-title":"Acylcarnitines: Nomenclature, Biomarkers, Therapeutic Potential, Drug Targets, and Clinical Trials","volume":"74","author":"Dambrova","year":"2022","journal-title":"Pharmacol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.mam.2011.10.008","article-title":"The mitochondrial carnitine\/acylcarnitine carrier: Function, structure and physiopathology","volume":"32","author":"Indiveri","year":"2011","journal-title":"Mol. Aspects Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1096\/fasebj.7.11.8370473","article-title":"Regulation of the long-chain carnitine acyltransferases","volume":"7","author":"Brady","year":"1993","journal-title":"FASEB J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1136\/adc.2009.174342","article-title":"How to use acylcarnitine profiles to help diagnose inborn errors of metabolism","volume":"95","author":"Santra","year":"2010","journal-title":"Arch. Dis. Child Educ. Pract. Ed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2337\/db12-0466","article-title":"Acylcarnitines: Reflecting or inflicting insulin resistance?","volume":"62","author":"Schooneman","year":"2013","journal-title":"Diabetes"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Li, S., Gao, D., and Jiang, Y. (2019). Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma. Metabolites, 9.","DOI":"10.3390\/metabo9020036"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6671","DOI":"10.3748\/wjg.v11.i42.6671","article-title":"Plasma carnitine ester profile in adult celiac disease patients maintained on long-term gluten free diet","volume":"11","author":"Bene","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Miyaaki, H., Kobayashi, H., Miuma, S., Fukusima, M., Sasaki, R., Haraguchi, M., and Nakao, K. (2020). Blood carnitine profiling on tandem mass spectrometry in liver cirrhotic patients. BMC Gastroenterol., 20.","DOI":"10.1186\/s12876-020-01190-6"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"G194","DOI":"10.1152\/ajpgi.00413.2005","article-title":"Lipid metabolism and liver inflammation","volume":"290","author":"Bradbury","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1055\/s-0030-1253227","article-title":"The role of inflammation in cholestasis","volume":"30","author":"Kosters","year":"2010","journal-title":"Semin. Liver Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12093","DOI":"10.1074\/jbc.M510660200","article-title":"Free fatty acids induce JNK-dependent hepatocyte lipoapoptosis","volume":"281","author":"Malhi","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/hep.20283","article-title":"Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway","volume":"40","author":"Feldstein","year":"2004","journal-title":"Hepatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1016\/j.cmet.2021.06.012","article-title":"FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption","volume":"33","author":"Clifford","year":"2021","journal-title":"Cell Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1089\/1044549041562267","article-title":"Polyunsaturated fatty acids are FXR ligands and differentially regulate expression of FXR targets","volume":"23","author":"Zhao","year":"2004","journal-title":"DNA Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e100074","DOI":"10.1136\/egastro-2024-100074","article-title":"Bile acids regulation of cellular stress responses in liver physiology and diseases","volume":"2","author":"Li","year":"2024","journal-title":"eGastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102328","DOI":"10.1016\/j.jaut.2019.102328","article-title":"The challenges of primary biliary cholangitis: What is new and what needs to be done","volume":"105","author":"Vergani","year":"2019","journal-title":"J. Autoimmun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/hep.1840170408","article-title":"Cholesterol-Lowering Effect of Ursodeoxycholic Acid in Patients with Primary Biliary Cirrhosis","volume":"17","author":"Poupon","year":"1993","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJMoa1509840","article-title":"A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis","volume":"375","author":"Nevens","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0022-2275(20)31668-0","article-title":"Cholesterol Metabolism in Primary Biliary Cirrhosis during Simvastatin and UDCA Administration","volume":"42","author":"Crosignani","year":"2001","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1136\/flgastro-2018-101124","article-title":"Hyperlipidaemia in Primary Biliary Cholangitis: Treatment, Safety and Efficacy","volume":"10","author":"Danford","year":"2019","journal-title":"Frontline Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2019). EASL Clinical Practice Guidelines on Nutrition in Chronic Liver Disease. J. Hepatol., 70, 172\u2013193.","DOI":"10.1016\/j.jhep.2018.06.024"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Felice, F.D., Malerba, S., Nardone, V., Salvestrini, V., Calomino, N., Testini, M., Boccardi, V., Desideri, I., Gentili, C., and De Luca, R. (2025). Progress and Challenges in Integrating Nutritional Care into Oncology Practice: Results from a National Survey on Behalf of the NutriOnc Research Group. Nutrients, 17.","DOI":"10.3390\/nu17010188"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/7\/1097\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:57:34Z","timestamp":1760029054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/7\/1097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":30,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["nu17071097"],"URL":"https:\/\/doi.org\/10.3390\/nu17071097","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,21]]}}}