{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:54:03Z","timestamp":1790970843236,"version":"4.1.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":85,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Gansu Province Health and Wellness Industry Research Project","award":["GSWSQN2024-02"],"award-info":[{"award-number":["GSWSQN2024-02"]}]},{"name":"Gansu Provincial Natural Science Foundation","award":["26JRRA823"],"award-info":[{"award-number":["26JRRA823"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Gastroenterol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To validate the analytical performance of the Roche cobas e 801 chemiluminescent immunoassay for Protein induced by vitamin K absence or antagonist-II (PIVKA-II), establish age-\/gender-specific reference intervals for healthy adults in the Gansu population, and evaluate its concordance with the Abbott Alinity i system currently used in our laboratory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Precision (intra-run\/inter-run coefficients of variation [CVs]), linearity (0.50-12000 ng\/mL), and clinical reportable range (via 10-fold dilution with 80%-120% recovery criteria) were verified following Clinical and Laboratory Standards Institute (CLSI) and Chinese health industry standards. Agreement between the cobas e 801 and Alinity i systems was assessed using Passing-Bablok regression and Bland-Altman analysis (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009173). Reference intervals were established based on 2253 healthy participants (\u2265\u200918 years, permanent residents of Lanzhou). The 2.5th-97.5th percentiles were calculated using a nonparametric method, and decision tree analysis was used to determine age stratification cutoffs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Intra-run coefficients of variation ranged from 1.36% to 1.57%, and inter-run CVs from 1.13% to 1.16%, all below CLIA\u201988 total allowable error and manufacturer claims (except for intra-run high-value quality control (QC), which was slightly higher than the manufacturer\u2019s specification). The linear regression equation was Y\u2009=\u20090.99X\u2009+\u20096.34 (R\n                      <jats:sup>2<\/jats:sup>\n                      = 0.99), and deviations at all concentration points were &lt;\u20091\/2 Total allowable error (Tea) (11%), meeting linearity requirements. Recoveries after 10-fold dilution ranged from 89.62% to 92.16%, validating the clinical reportable range of 15.30-91533.33 ng\/mL. Verification using 20 healthy individuals showed that 100% of results were below the manufacturer\u2019s reference interval upper limit (&lt;\u200928.4 ng\/mL). Method comparison revealed that the intercept 95% confidence interval (CI) (-2.16 to 3.42) included 0, indicating no significant constant (systematic) error, while the slope 95% CI (0.4693 to 0.6925) did not include 1, indicating significant proportional bias. Bland-Altman analysis showed that 96.50% (167\/173) of data points fell within the limits of agreement, indicating good agreement between the two methods. The reference interval for males (\u2265\u200918 years) was 9.63\u201329.10 ng\/mL, with no age stratification required. For females, age-stratified reference intervals were established: 9.50\u201326.30 ng\/mL for ages 18\u201354 years, and 9.42-30.00 ng\/mL for ages\u2009\u2265\u200955 years. We recommend a unified reference interval of 9.52\u201329.10 ng\/mL for routine clinical use. Age- and sex-stratified intervals are statistically significant but have modest clinical impact (\u223c3 ng\/mL difference in upper limits).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The PIVKA-II assay on the Roche cobas e 801 system meets laboratory quality requirements for analytical performance and is suitable for clinical application. Due to significant proportional bias compared with the Abbott Alinity i system, system-specific reference intervals are recommended, and the two systems should not be used interchangeably. For results approaching the upper reference limit, clinical follow-up is advised. The established local reference intervals can provide more targeted decision-making support for hepatocellular carcinoma screening.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12876-026-05088-7","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:46:10Z","timestamp":1783593970000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assay performance verification and reference interval establishment for PIVKA-II on the Roche cobas e 801"],"prefix":"10.1186","volume":"26","author":[{"given":"Youli","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zejing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhong","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"issue":"Pt3","key":"5088_CR1","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.semcancer.2021.07.017","volume":"86","author":"GP Nagaraju","year":"2022","unstructured":"Nagaraju GP, Dariya B, Kasa P, Peela S, El-Rayes BF. Epigenetics in hepatocellular carcinoma. Sem Cancer Biol. 2022;86(Pt3):622\u201332.","journal-title":"Sem Cancer Biol"},{"issue":"2","key":"5088_CR2","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1159\/000537897","volume":"13","author":"M Kudo","year":"2024","unstructured":"Kudo M. Urgent global need for PIVKA-II and AFP-L3 measurements for surveillance and management of hepatocellular carcinoma. Liver Cancer. 2024;13(2):113\u20138.","journal-title":"Liver Cancer"},{"key":"5088_CR3","doi-asserted-by":"crossref","unstructured":"Zhou Z, Liu Q, Liu J, Li W, Cao S, Xu J et al. Research progress of protein induced by vitamin K absence or antagonist II in liver transplantation for hepatocellular carcinoma. Heliyon. 2024;10(9):e30622.","DOI":"10.1016\/j.heliyon.2024.e30622"},{"issue":"3","key":"5088_CR4","first-page":"532","volume":"15","author":"National Health Commission of the People\u2019s Republic of China","year":"2024","unstructured":"National Health Commission of the People\u2019s Republic of China. Guideline for diagnosis and treatment of primary liver cancer (2024 edition). Med J Peking Union Med Coll Hosp. 2024;15(3):532\u201359.","journal-title":"Med J Peking Union Med Coll Hosp"},{"issue":"5","key":"5088_CR5","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1002\/jgh3.12720","volume":"6","author":"HLY Chan","year":"2022","unstructured":"Chan HLY, Vogel A, Berg T, De Toni EN, Kudo M, Trojan J, et al. Performance evaluation of the Elecsys PIVKA-II and Elecsys AFP assays for hepatocellular carcinoma diagnosis. JGH Open. 2022;6(5):292\u2013300.","journal-title":"JGH Open"},{"key":"5088_CR6","unstructured":"National Committee for Clinical Laboratory Standards. User demonstration of performance for precision and accuracy (EP15-A2). NCCLS; 2001."},{"key":"5088_CR7","unstructured":"National Health Commission of the People\u2019s Republic of China. WS\/T 408\u20132024 Guideline for the verification of analytical performance of quantitative examination procedures. 2024."},{"key":"5088_CR8","unstructured":"National Health Commission of the People\u2019s Republic of China. WS\/T 415\u20132024 Clinical laboratory quality evaluation in the absence of external quality assessment. 2024."},{"key":"5088_CR9","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.cca.2020.06.035","volume":"509","author":"J-L Bayart","year":"2020","unstructured":"Bayart J-L, Mairesse A, Gruson D, van Dievoet M-A. Analytical performances and biological variation of PIVKA-II (des-\u03b3-carboxy-prothrombin) in European healthy adults. Clin Chim Acta. 2020;509:264\u20137.","journal-title":"Clin Chim Acta"},{"key":"5088_CR10","unstructured":"China National Accreditation Service for Conformity Assessment. CNAS-GL037 Guidance on the verification of quantitative measurement procedures in clinical chemistry. 2019."},{"key":"5088_CR11","unstructured":"National Health Commission of the People\u2019s Republic of China. Establishment of reference intervals for quantitative items in clinical laboratory: WS\/T 402\u20132024. Standards Press of China; 2024."},{"key":"5088_CR12","unstructured":"Clinical and Laboratory Standards Institute. Defining, establishing, and verifying reference intervals (EP28-A3c). CLSI; 2010."},{"issue":"1","key":"5088_CR13","doi-asserted-by":"publisher","first-page":"49","DOI":"10.11613\/BM.2011.010","volume":"21","author":"L Bili\u0107-Zulle","year":"2011","unstructured":"Bili\u0107-Zulle L. Comparison of methods: Passing and Bablok regression. Biochemia Med. 2011;21(1):49\u201352.","journal-title":"Biochemia Med"},{"key":"5088_CR14","doi-asserted-by":"crossref","unstructured":"Panda SK, Gaurav A, Das P, Swain N, Rath S. A comparison between transcutaneous bilirubin and total serum bilirubin levels for the management of jaundice in preterm neonates by Bland-Altman plot. Cureus. 2021;13(10):e18442.","DOI":"10.7759\/cureus.18442"},{"issue":"3","key":"5088_CR15","first-page":"20200063","volume":"1","author":"J D\u00edaz-Garz\u00f3n Marco","year":"2020","unstructured":"D\u00edaz-Garz\u00f3n Marco J, Fern\u00e1ndez-Calle P, Ric\u00f3s C. Models to estimate biological variation components and interpretation of serial results: Strengths and limitations. Adv Lab Med. 2020;1(3):20200063.","journal-title":"Adv Lab Med"},{"issue":"1","key":"5088_CR16","first-page":"75","volume":"48","author":"D-H Ko","year":"2018","unstructured":"Ko D-H, Hyun J, Kim HS, Park M-J, Kim J-S, Park J-Y, et al. Analytical and clinical performance evaluation of the Abbott Architect PIVKA assay. Annals Clin Lab Sci. 2018;48(1):75\u201380.","journal-title":"Annals Clin Lab Sci"},{"issue":"3","key":"5088_CR17","first-page":"372","volume":"49","author":"S Lim","year":"2019","unstructured":"Lim S, Lee K, Woo H-Y, Park H, Kwon M-J. Evaluation of Cobas 8000 Analyzer Series Module e 801 analytical performance. Annals Clin Lab Sci. 2019;49(3):372\u20139.","journal-title":"Annals Clin Lab Sci"},{"key":"5088_CR18","doi-asserted-by":"publisher","first-page":"110863","DOI":"10.1016\/j.clinbiochem.2024.110863","volume":"135","author":"E Shang","year":"2025","unstructured":"Shang E, Agustin H, Lee JKY, Scheidegger M, Jones J, Abou-Diwan C, et al. Evaluation of Siemens Atellica AMH assay and comparison with Roche, Beckman and Ansh Labs. Clin Biochem. 2025;135:110863.","journal-title":"Clin Biochem"},{"issue":"5","key":"5088_CR19","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.jmoldx.2019.04.002","volume":"21","author":"J Schreier","year":"2019","unstructured":"Schreier J, Feeney R, Keeling P. Diagnostics reform and harmonization of clinical laboratory testing. J Mol Diagn. 2019;21(5):737\u201345.","journal-title":"J Mol Diagn"},{"issue":"8","key":"5088_CR20","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1373\/clinchem.2011.164012","volume":"57","author":"WG Miller","year":"2011","unstructured":"Miller WG, Myers GL, Gantzer ML. Roadmap for harmonization of clinical laboratory measurement procedures. Clin Chem. 2011;57(8):1108\u201317.","journal-title":"Clin Chem"},{"issue":"Suppl 3","key":"5088_CR21","doi-asserted-by":"publisher","first-page":"S907","DOI":"10.3945\/ajcn.115.110387","volume":"104","author":"HW Vesper","year":"2016","unstructured":"Vesper HW, Myers GL, Miller WG. Current practices and challenges in the standardization and harmonization of clinical laboratory tests. Am J Clin Nutr. 2016;104(Suppl 3):S907\u201312.","journal-title":"Am J Clin Nutr"},{"key":"5088_CR22","unstructured":"National Health Commission of the People\u2019s Republic of China. WS\/T 407\u20132022 Requirements for result comparability between clinical laboratory testing systems. Standards Press of China; 2022."},{"key":"5088_CR23","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.clinbiochem.2018.02.007","volume":"54","author":"C Yan","year":"2018","unstructured":"Yan C, Hu J, Yang J, et al. Serum ARCHITECT PIVKA-II reference interval in healthy Chinese adults: Sub-analysis from a prospective multicenter study. Clin Biochem. 2018;54:32\u20136.","journal-title":"Clin Biochem"},{"issue":"4","key":"5088_CR24","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1111\/ijlh.12639","volume":"39","author":"X Qin","year":"2017","unstructured":"Qin X, Tang G, Gao R, et al. A multicenter study on PIVKA reference interval of healthy population and establishment of PIVKA cutoff value for hepatocellular carcinoma diagnosis in China. Int J Lab Hematol. 2017;39(4):392\u2013401.","journal-title":"Int J Lab Hematol"},{"issue":"6","key":"5088_CR25","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.clinbiochem.2016.11.036","volume":"50","author":"J Liu","year":"2017","unstructured":"Liu J, Yu X, Xia M, et al. Development of gestation-specific reference intervals for thyroid hormones in normal pregnant Northeast Chinese women. Clin Biochem. 2017;50(6):309\u201317.","journal-title":"Clin Biochem"},{"issue":"3","key":"5088_CR26","first-page":"232","volume":"19","author":"ZK Jiang","year":"2020","unstructured":"Jiang ZK, Zhao Y, Xu F, et al. Reference intervals for tumor biomarkers AFP, PIVKA-II and AFU in Shanghai area. J Clin Experimental Med. 2020;19(3):232\u20136.","journal-title":"J Clin Experimental Med"},{"issue":"6","key":"5088_CR27","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13020-023-00875-w","volume":"30","author":"QM Yang","year":"2024","unstructured":"Yang QM, Su JH, Chen YM, et al. Establishment and discussion of PIVKA-II common reference interval of healthy population in the medical union area of Tongan District General Hospital of Xiamen City. China Med Device Inform. 2024;30(6):4\u20136.","journal-title":"China Med Device Inform"}],"container-title":["BMC Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12876-026-05088-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-026-05088-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-026-05088-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:02:14Z","timestamp":1790967734000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12876-026-05088-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5088"],"URL":"https:\/\/doi.org\/10.1186\/s12876-026-05088-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-8668056\/v1","asserted-by":"object"}]},"ISSN":["1471-230X"],"issn-type":[{"value":"1471-230X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]},"assertion":[{"value":"22 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was reviewed and approved by The Second Hospital & Clinical Medical School, Lanzhou University Medical Ethics Committee (approval number: 2023\u00a0A-459). All participants voluntarily signed informed consent forms after fully understanding the content of the study. This research complies with the Helsinki Declaration.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This manuscript has not been published or presented elsewhere in part or in entirety, and is not under consideration by another journal. All the authors have approved the manuscript and agree with submission to your esteemed journal.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"602"}}