Evidence map›Paper›PMID 37333414›Full record

ArticlemedRxiv : the preprint server for health sciences2023

Intrahepatic transcriptomics differentiate advanced fibrosis and clinical outcomes in adults with the Fontan circulation.

Katia Bravo-Jaimes, Xiuju Wu, Leigh C Reardon, Gentian Lluri, Jeannette P Lin, Jeremy P Moore, Glen Van Arsdell, Reshma Biniwale, Ming-Sing Si, Bita V Naini and 9 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 1 institution in 1 country.

Katia Bravo-JaimesDepartment of Cardiovascular Diseases. Mayo Clinic Jacksonville Florida.
Xiuju WuDivision of Cardiology. Department of Medicine. University of California, Los Angeles.
Leigh C ReardonAhmanson/UCLA Adult Congenital Heart Disease Center. University of California, Los Angeles.
Gentian LluriAhmanson/UCLA Adult Congenital Heart Disease Center. University of California, Los Angeles.
Jeannette P LinAhmanson/UCLA Adult Congenital Heart Disease Center. University of California, Los Angeles.
Jeremy P MooreAhmanson/UCLA Adult Congenital Heart Disease Center. University of California, Los Angeles.
Glen Van ArsdellAhmanson/UCLA Adult Congenital Heart Disease Center. University of California, Los Angeles.
Reshma BiniwaleDepartment of Cardiovascular Diseases. Mayo Clinic Jacksonville Florida.
Ming-Sing SiDepartment of Cardiovascular Diseases. Mayo Clinic Jacksonville Florida.
Bita V NainiDepartment of Pathology and Lab Services. University of California, Los Angeles.
Robert VenickDepartment of Gastroenterology, Hepatology and Nutrition. University of California, Los Angeles Mattel Children's Hospital.
Sammy SaabDepartment of Gastroenterology, Hepatology and Nutrition. University of California, Los Angeles Mattel Children's Hospital.
Christopher L WrayDepartment of Anesthesiology. University of California, Los Angeles.
Reid PonderAhmanson/UCLA Adult Congenital Heart Disease Center. University of California, Los Angeles.
Carl RosenthalDumont-UCLA Liver Transplant Center. Department of Surgery. University of California, Los Angeles.
Alexandra KlomhausDepartment of Medicine Statistics Core. David Geffen School of Medicine. University of California, Los Angeles.
Kristina I BöstromDivision of Cardiology. Department of Medicine. University of California, Los Angeles.
Jamil A AboulhosnAhmanson/UCLA Adult Congenital Heart Disease Center. University of California, Los Angeles.
Fady M KaldasDumont-UCLA Liver Transplant Center. Department of Surgery. University of California, Los Angeles.
University of California, Los Angeles · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Molecular Mechanisms of MGP; Role in AVMsR01HL081397 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOSTROM, KRISTINA I · 2006 to 2025
$7.7M
Endothelial Regulation of Vascular CalcificationR01HL158053 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOSTROM, KRISTINA I · 2022 to 2025
$2.2M
NCATS NIH HHS UL1 TR001881NHLBI NIH HHS R01 HL081397NHLBI NIH HHS R01 HL158053
6 · The paper itself

Abstract

Background: The molecular mechanisms underlying Fontan associated liver disease (FALD) remain largely unknown. We aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. Methods: This retrospective cohort study included adults with the Fontan circulation at the Ahmanson/UCLA Adult Congenital Heart Disease Center. Clinical, laboratory, imaging and hemodynamic data prior to the liver biopsy were extracted from medical records. Patients were classified into early (F1-F2) or advanced fibrosis (F3-F4). RNA was isolated from formalin-fixed paraffin embedded liver biopsy samples; RNA libraries were constructed using rRNA depletion method and sequencing was performed on Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were carried out using DESeq2 and Metascape. Medical records were comprehensively reviewed for a composite clinical outcome which included decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, protein-losing enteropathy, chronic kidney disease stage 4 or higher, or death. Results: Patients with advanced fibrosis had higher serum BNP levels and Fontan, mean pulmonary artery and capillary wedge pressures. The composite clinical outcome was present in 23 patients (22%) and was predicted by age at Fontan, right ventricular morphology and presence of aortopulmonary collaterals on multivariable analysis. Samples with advanced fibrosis had 228 up-regulated genes compared to early fibrosis. Samples with the composite clinical outcome had 894 up-regulated genes compared to those without it. A total of 136 up-regulated genes were identified in both comparisons and these genes were enriched in cellular response to cytokine stimulus, response to oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-beta signaling pathway, and vasculature development. Conclusions: Patients with FALD and advanced liver fibrosis or the composite clinical outcome exhibit up-regulated genes including pathways related to inflammation, congestion, and angiogenesis. This adds further insight into FALD pathophysiology.

Indexed as

Fontan-associated liver diseaseFontan outcomesliver fibrosissingle ventricletranscriptomics

Identifiers

PMID37333414
PMCPMC10274997
OpenAlexW4379645102

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.