{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:36:01Z","timestamp":1783571761964,"version":"3.55.0"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Saarland University Medical Center\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/01jdpyv68","award":["HOMFOR T201000779"],"award-info":[{"award-number":["HOMFOR T201000779"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/018mejw64","doi-asserted-by":"publisher","award":["VO 1355\/5-2"],"award-info":[{"award-number":["VO 1355\/5-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Elevated levels of the C-3 epimer (3-epi-25(OH)D) of 25-hydroxyvitamin D (25(OH)D) have been identified in premature infants as compared to most adults, and an immature liver has been suggested as a possible cause. We hypothesised that patients with cirrhosis might present with elevated C-3 epimerisation due to impaired liver function. The aim was to assess whether 3-epi-25(OH)D levels differ in patients with chronic liver disease with cirrhosis vs. those without cirrhosis. Methods: A total of 309 patients were included (254 patients with cirrhosis vs. 55 without cirrhosis). Serum 25(OH)D and 3-epi-25(OH)D levels were determined using liquid chromatography-tandem mass spectrometry (LC-MS\/MS). Results: Patients with cirrhosis had significantly higher median relative 3-epi-25(OH)D concentrations, as compared to patients without cirrhosis (7.4% (5.5\u201310.4) vs. 4.8% (2.4\u20135.7), respectively; p &lt; 0.001). They also had similar absolute 3-epi-25(OH)D levels (despite having lower 25(OH)D serum concentrations) than patients without cirrhosis. A progressive increase in relative 3-epi-25(OH)D levels was observed with more advanced cirrhosis (p &lt; 0.001). An analysis of the ROC area under the curve determined 6% as the optimal cut-off for relative 3-epi-25(OH)D. All patients with Child\u2013Pugh stage C and 88.6% with stage B were above the 6% cut-off and had significantly higher absolute serum 3-epi-25(OH)D concentrations (0.9 ng\/mL vs. 0.6 ng\/mL; p &lt; 0.05) and lower serum 25(OH)D levels (9.3 vs. 14.1 ng\/mL; p &lt; 0.001) than patients &lt;6% cut-off. Conclusions: These results reflect the marked increases in relative 3-epi-25(OH)D levels that occur with cirrhosis. The specific hepatic metabolic alterations still need to be unravelled, including whether cirrhosis might lead to reduced epimer clearance.<\/jats:p>","DOI":"10.3390\/nu18071071","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:45:53Z","timestamp":1774615553000},"page":"1071","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Elevated Relative Levels of the C-3 Epimer of 25-Hydroxyvitamin D in Patients with Cirrhosis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3861-254X","authenticated-orcid":false,"given":"Caroline S.","family":"Stokes","sequence":"first","affiliation":[{"name":"Food and Health Research Group, Faculty of Life Sciences, Humboldt University Berlin, 14195 Berlin, Germany"},{"name":"Department of Medicine II, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8192-0575","authenticated-orcid":false,"given":"Matthias C.","family":"Reichert","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Schorr","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Humboldt University Berlin, 12489 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0750-0329","authenticated-orcid":false,"given":"Frank","family":"Gr\u00fcnhage","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2820-1480","authenticated-orcid":false,"given":"Dietrich A.","family":"Volmer","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Humboldt University Berlin, 12489 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Lammert","sequence":"additional","affiliation":[{"name":"Center for Health Economics Research Hannover (CHERH), Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/liv.12106","article-title":"Vitamin D in chronic liver disease","volume":"33","author":"Stokes","year":"2013","journal-title":"Liver Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1002\/mas.21768","article-title":"Analysis of vitamin D metabolic markers by mass spectrometry: Recent progress regarding the \u201cgold standard\u201d method and integration into clinical practice","volume":"42","author":"Alexandridou","year":"2023","journal-title":"Mass Spectrom. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.clnu.2013.06.005","article-title":"Epidemiologic study of the C-3 epimer of 25-hydroxyvitamin D(3) in a population-based sample","volume":"33","author":"Engelman","year":"2014","journal-title":"Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1210\/jc.2011-0584","article-title":"The C-3 epimer of 25-hydroxyvitamin D(3) is present in adult serum","volume":"97","author":"Lensmeyer","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"23004","DOI":"10.1038\/s41598-023-50524-3","article-title":"C3-epi-25(OH)D3 percentage, not level, may be a potential biomarker to reflect its pathological increase in multiple diseases: A cross-sectional case-control study","volume":"13","author":"Chen","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.clinbiochem.2018.02.013","article-title":"C3-epimerization of 25-hydroxyvitamin D increases with increasing serum 25-hydroxyvitamin D levels and shows a high degree of tracking over time","volume":"54","author":"Kubiak","year":"2018","journal-title":"Clin. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1139\/apnm-2013-0586","article-title":"Plasma 25-hydroxyvitamin D, more so than its epimer, has a linear relationship to leaner body composition across infancy in healthy term infants","volume":"39","author":"Hazell","year":"2014","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jchromb.2014.07.021","article-title":"Overestimation of 25-hydroxyvitamin D3 by increased ionisation efficiency of 3-epi-25-hydroxyvitamin D3 in LC-MS\/MS methods not separating both metabolites as determined by an LC-MS\/MS method for separate quantification of 25-hydroxyvitamin D3, 3-epi-25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in human serum","volume":"967","author":"Beijers","year":"2014","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1210\/jc.2013-3953","article-title":"Case report: Three patients with substantial serum levels of 3-epi-25(OH)D including one with 3-epi-25(OH)D2 while on high-dose ergocalciferol","volume":"99","author":"Wiebe","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1475-2891-10-46","article-title":"Misleading measures in Vitamin D analysis: A novel LC-MS\/MS assay to account for epimers and isobars","volume":"10","author":"Shah","year":"2011","journal-title":"Nutr. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1210\/jc.2006-0710","article-title":"C-3 epimers can account for a significant proportion of total circulating 25-hydroxyvitamin D in infants, complicating accurate measurement and interpretation of vitamin D status","volume":"91","author":"Singh","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yang, T., Chen, X., Wang, M., Xu, S., Hu, D., Tang, J., and Yang, Y. (2024). Differential performance regarding the relationship of C3-epi-25(OH)D3 levels and %C3-epi-25(OH)D3 with common pediatric diseases: A case control study. BMC Pediatr., 24.","DOI":"10.1186\/s12887-024-05072-8"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1186\/s40001-024-02212-9","article-title":"Differential seasonal performance of C3-epi-D3 level and proportion on multiple metabolic disorders in patients with type 2 diabetes mellitus","volume":"29","author":"Chen","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5268706","DOI":"10.1155\/2022\/5268706","article-title":"C3-Epimer of 25-Hydroxyvitamin D3 as a Superior Marker for Predicting the Severity of Chronic Kidney Disease in Rheumatoid Arthritis Patients","volume":"2022","author":"Tang","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1001\/jama.2013.3404","article-title":"Effect of different dosages of oral vitamin D supplementation on vitamin D status in healthy, breastfed infants: A randomized trial","volume":"309","author":"Gallo","year":"2013","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/pr.2015.251","article-title":"Time-course analysis of 3-epi-25-hydroxyvitamin D3 shows markedly elevated levels in early life, particularly from vitamin D supplementation in preterm infants","volume":"79","author":"Ooms","year":"2016","journal-title":"Pediatr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.abb.2019.03.010","article-title":"Catalytic properties of 25-hydroxyvitamin D3 3-epimerase in rat and human liver microsomes","volume":"666","author":"Tuckey","year":"2019","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1139\/apnm-2016-0196","article-title":"Assessment of 3-epi-25-hydroxyvitamin D levels during cholecalciferol supplementation in adults with chronic liver diseases","volume":"41","author":"Stokes","year":"2016","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.clnu.2015.07.004","article-title":"Vitamin D supplementation reduces depressive symptoms in patients with chronic liver disease","volume":"35","author":"Stokes","year":"2016","journal-title":"Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1002\/hep.25830","article-title":"Common genetic variation in vitamin D metabolism is associated with liver stiffness","volume":"56","author":"Grunhage","year":"2012","journal-title":"Hepatology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"50660","DOI":"10.1021\/acsomega.4c08675","article-title":"Streamlined Vitamin D Metabolite Fingerprinting Analysis Using Isotope-Coded Multiplexing MS with Cost-Effective One-Pot Double Derivatization","volume":"9","author":"Schorr","year":"2024","journal-title":"ACS Omega"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115522","DOI":"10.1016\/j.jpba.2023.115522","article-title":"Improved quantitative LC-MS\/MS analysis of vitamin D metabolites in serum after one-pot double derivatization","volume":"234","author":"Schorr","year":"2023","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"570","DOI":"10.14309\/ajg.0000000000002953","article-title":"The Liver Cirrhosis Network Cohort Study: Cirrhosis Definition, Study Population, and Endpoints","volume":"120","author":"Tapper","year":"2025","journal-title":"Am. J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.clinbiochem.2014.01.015","article-title":"Maternal-fetal-infant dynamics of the C3-epimer of 25-hydroxyvitamin D","volume":"47","author":"Bailey","year":"2014","journal-title":"Clin. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_27","unstructured":"Tsoris, A., and Marlar, C.A. (2024). Use of The Child Pugh Score in Liver Disease, StatPearls."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.3945\/jn.114.192419","article-title":"The 3 epimer of 25-hydroxycholecalciferol is present in the circulation of the majority of adults in a nationally representative sample and has endogenous origins","volume":"144","author":"Cashman","year":"2014","journal-title":"J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jsbmb.2018.09.003","article-title":"The serum vitamin D metabolome: What we know and what is still to discover","volume":"186","author":"Tuckey","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_30","first-page":"36","article-title":"The genetic determinants of circulating C3-epimers of 25-hydroxyvitamin D","volume":"12","author":"Torugsa","year":"2018","journal-title":"J. Clin. Transl. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1210\/clinem\/dgae290","article-title":"Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline","volume":"109","author":"Demay","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/7\/1071\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:59:19Z","timestamp":1774616359000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/7\/1071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,27]]},"references-count":31,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["nu18071071"],"URL":"https:\/\/doi.org\/10.3390\/nu18071071","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,27]]}}}