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Record W4294916329 · doi:10.1002/hep.32777

Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease

2022· article· en· W4294916329 on OpenAlexaff
Daniel H. Leung, Sridevi Devaraj, Nathan P. Goodrich, Xinpu Chen, Deepthi Rajapakshe, Wen Ye, Victor P. Andreev, Charles G. Minard, Danielle Guffey, Jean P. Molleston, Lee M. Bass, Saul J. Karpen, Binita M. Kamath, Kasper S. Wang, Shikha S. Sundaram, Philip Rosenthal, Patrick McKiernan, Kathleen M. Loomes, M. Kyle Jensen, Simon Horslen, Jorge A. Bezerra, John C. Magee, Robert M. Merion, Ronald J. Sokol, Benjamin L. Shneider, Estella M. Alonso, Susan Kelly, Mary M. Riordan, Héctor Melín‐Aldana, Kevin E. Bove, James E. Heubi, Alexander Miethke, Greg Tiao, J. Kenneth Denlinger, Erin D. Chapman, Amy G. Feldman, Cara L. Mack, Michael R. Narkewicz, Frederick J. Suchy, Johan Van Hove, B. Valdes Garcia, Mikaela Kauma, Kendra Kocher, Matthew Steinbeiss, Mark A. Lovell, David A. Piccoli, Elizabeth R. Rand, Pierre Russo, Nancy B. Spinner, Jessi Erlichman, Samantha Stalford, Dina Pakstis, Sakya King, Robert H. Squires, Rakesh Sindhi, Veena Venkat, Kathy Bukauskas, Lori Haberstroh, James E. Squires, Laura N. Bull, Joanna Curry, Camille Langlois, Grace Kim, Jeffrey Teckman, Vikki Kociela, Rosemary Nagy, Shraddha Patel, Jacqueline Cerkoski, Molly Bozic, Girish Subbarao, Ann Klipsch, Cindy Sawyers, Oscar W. Cummings, Karen F. Murray, Evelyn Hsu, Kara Cooper, Melissa Young, Laura S. Finn, Vicky L. Ng, Claudia Quammie, Juan Putra, Deepika Sharma, Aishwarya Parmar, Stephen L. Guthery, Kyle Jensen, Ann Rutherford, Amy Lowichik, Linda Book, Rebecka L. Meyers, Tyler Hall, Sonia Michail, Danny G. Thomas, Catherine J. Goodhue, Rohit Kohli, Larry Wang, Nisreen Soufi, D. Thomas, Nitika Gupta, René Romero, Miriam B. Vos, Rita Tory, John‐Paul Berauer, Carlos R. Abramowsky, Jeanette McFall, Sanjiv Harpavat, Paula M. Hertel, Mary Elizabeth M. Tessier, Deborah Schady, Laurel Cavallo, Diego Olvera, Christina Banks, Cynthia M. Tsai, Richard J. Thompson, Edward Doo, Jay H. Hoofnagle, Averell H. Sherker, Rebecca Torrance, Sherry Hall, Cathie Spino

Bibliographic record

VenueHepatology · 2022
Typearticle
Languageen
FieldMedicine
TopicPediatric Hepatobiliary Diseases and Treatments
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
FundersNational Center for Research ResourcesAgency for Healthcare Research and QualityNational Center for Advancing Translational SciencesAudentes TherapeuticsNational Institute of Diabetes and Digestive and Kidney DiseasesGilead Sciences
KeywordsCTGFBiomarkerMedicineInternal medicineGastroenterologyLiver diseasePeriostinTIMP1FibrosisCholestasisBiliary atresiaPathologyGrowth factorExtracellular matrixBiologyLiver transplantationReceptor

Abstract

fetched live from OpenAlex

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis. APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin ( p = 0.04) and IL-8 ( p < 0.001) and MMP-7 ( p < 0.001) in participants with BA. The best prediction model for LSM in BA using clinical and lab measurements had an R2 = 0.437; adding IL-8 and MMP-7 improved R2 to 0.523 and 0.526 (both p < 0.0001). In participants with A1AT, CTGF and LSM were negatively correlated ( p = 0.004); adding CTGF to an LSM prediction model improved R2 from 0.524 to 0.577 ( p = 0.0033). Biomarkers did not correlate with LSM in ALGS. A significant number of biomarker/lab correlations were found in participants with BA but not those with A1AT or ALGS. CONCLUSIONS: Endoglin, IL-8, and MMP-7 significantly correlate with increased LSM in children with BA, whereas CTGF inversely correlates with LSM in participants with A1AT; these biomarkers appear to enhance prediction of LSM beyond clinical tests. Future disease-specific investigations of change in these biomarkers over time and as predictors of clinical outcomes will be important.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.014
Threshold uncertainty score0.763

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.018
GPT teacher head0.265
Teacher spread0.247 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations28
Published2022
Admission routes1
Has abstractyes

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