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Record W4210638873 · doi:10.1093/ecco-jcc/jjab232.195

P066 Lower serum concentration of sulfated bile acids is associated with Primary Sclerosing Cholangitis Inflammatory Bowel Disease comorbidity and advanced liver fibrosis

2022· article· en· W4210638873 on OpenAlexaffabout
Haim Leibovitzh, Shadi Nayeri, Krzysztof Borowski, Cristian Hernández-Rocha, S H Lee, Williams Turpin, Joanne M. Stempak, Irwindeep Sandhu, Raquel Milgrom, Michelle I. Smith, Kenneth Croitoru, Gideon M. Hirschfield, Aliya Gulamhusein, Mark S. Silverberg

Bibliographic record

VenueJournal of Crohn s and Colitis · 2022
Typearticle
Languageen
FieldMedicine
TopicLiver Diseases and Immunity
Canadian institutionsSinai Health SystemToronto Liver CentreLunenfeld-Tanenbaum Research InstituteUniversity of TorontoMount Sinai Hospital
Fundersnot available
KeywordsGastroenterologyMedicineInternal medicinePrimary sclerosing cholangitisUlcerative colitisUrsodeoxycholic acidInflammatory bowel diseaseOdds ratioBile acidFibrosisConfidence intervalDisease

Abstract

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Abstract Background Primary sclerosing cholangitis associated Inflammatory bowel disease (PSC-IBD) carries significant morbidity risk. Alterations in bile acid profiles has been shown to modulate chronic inflammation in IBD, but data in PSC-IBD comorbidity is scarce. We aimed to assess associations of serum and stool bile acids (BA) with PSC-IBD phenotype versus ulcerative colitis (UC) and the degree of liver fibrosis in PSC-IBD patients Methods In this cross-sectional study, bile acids were profiled in 52 PSC-IBD and 50 UC subjects. Quantitation of bile acids was performed by reversed phase ultrahigh performance liquid chromatography/multiple reaction monitoring mass spectrometry with negative ion detection (TMIC, Alberta, CA). After data filtering and normalization, 71 serum and 76 stool BA were available for analysis. Logistic regression was used to assess associations between BA levels and disease phenotype (PSC-IBD versus UC). Among the PSC-IBD group, linear regression was used to assess associations of fibrosis degree (severe (F4) versus no/mild (F0-3) fibrosis, measured by FibroScan®) with BA profile. Age, sex and ursodeoxycholic acid treatment were included as co-variates in all models and alkaline phosphatase (ALP) was added as co-variate for the liver fibrosis analysis. False discovery rate<0.05 was considered significant Results PSC-IBD and UC group had similar age and sex distribution. In the multivariable logistic regression, 26 serum BA were significantly associated with PSC-IBD (Figure 1). Decreased concentrations of taurine/glycine-primary BA [odds ratio(OR)=0.97, 95% confidence interval (CI) 0.95–0.99], taurine/glycine-secondary BA [OR=0.98, 95%CI 0.97–0.99] and sulfated-BA [OR=0.96, 95%CI 0.95–0.98], and increased concentrations of conjugated-BA [OR=1.02, 95%CI 1.01–1.03] and glucuronidated-BA [OR=1.06, 95%CI 1.02–1.1] were associated with PSC-IBD phenotype (q<0.05). Decreased sulfated-BA concentrations remained associated with PSC-IBD [OR=0.96, 95%CI 0.94–0.99, q=0.06] even among PSC-IBD subjects with normal ALP<2XULN (n=67). In contrast, stool BA analysis did not show significant associations with PSC-IBD versus UC. Additionally, in the PSC-IBD group, F4 fibrosis degree compared to F0-3 was associated with lower serum concentrations of taurine/glycine- and sulfated-BA, and higher serum concentrations of conjugated-BA (q<0.05) Conclusion Decreased concentration of sulfated-BA was associated with PSC-IBD phenotype with and without cholestasis compared to UC group. Lower sulfated-BA concentration was also associated with severe degree of liver fibrosis among PSC-IBD subjects. This inverse relationship between sulfated-BA levels and PSC-IBD and the degree of fibrosis should be further explored in future mechanistic studies

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.005
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0050.001

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 head0.010
GPT teacher head0.221
Teacher spread0.211 · 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 source (direct Gemma or distilled Codex), 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".

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Citations1
Published2022
Admission routes2
Has abstractyes

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