Evidence map›Paper›PMID 38055647›Full record

ArticleHepatology communications2023

Neonatal cholestasis in children with Alpha-1-AT deficiency is a risk for earlier severe liver disease with male predominance.

Jeffrey Teckman, Philip Rosenthal, Rosalinda V Ignacio, Cathie Spino, Lee M Bass, Simon Horslen, Kasper Wang, John C Magee, Saul Karpen, Akihiro Asai and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hepatology communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.3field-weighted citation impact, top 19% of its field
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

4 citing papers in PubMed, 4 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 15 institutions in 2 countries.

Jeffrey TeckmanDepartment of Pediatrics and Biochemistry, Saint Louis University, Cardinal Glennon Children's Hospital, Saint Louis, Missouri, USA.
Philip RosenthalDepartment of Pediatrics and Surgery, University of California San Francisco, San Francisco, California, USA.
Rosalinda V IgnacioDepartment of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
Cathie SpinoDepartment of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
Lee M BassDepartment of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Simon HorslenDepartment of Pediatric Gastroenterology and Hepatology, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, Washington, USA.
Kasper WangDepartment of Pediatric Gastroenterology, Children's Hospital Los Angeles, Los Angeles, California, USA.
John C MageeDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
Saul KarpenDepartment of Pediatrics, Emory University, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Akihiro AsaiDepartment of Gastroenterology, and Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Jean P MollestonDepartment of Pediatric Gastroenterology, Hepatology and Nutrition, James Whitcomb Riley Hospital for Children, Indianapolis, Indiana, USA.
Robert H SquiresDepartment of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Binita M KamathDivision of Pediatric Gastroenterology, Department of Pediatrics, Hepatology and Nutrition, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Stephen L GutheryDepartment of Pediatrics, University of Utah College of Medicine and Intermountain Primary Children's Hospital, Salt Lake City, Utah, USA.
Kathleen M LoomesDivision of Pediatric Gastroenterology, Department of Pediatrics, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Benjamin L ShneiderDepartment of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.
Ronald J SokolDepartment of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado, USA.
ChiLDReN (Childhood Liver Disease Research Network)
University of Michigan–Ann Arbor · USCardinal Glennon Children’s Medical Center · USChildren's Healthcare of Atlanta · USChildren's Hospital of Los Angeles · USChildren's Hospital of Philadelphia · USCincinnati Children's Hospital Medical Center · USNorthwestern University · USPrimary Children's Hospital · USRiley Hospital for Children · USTexas Children's Hospital · USUniversity of California, San Francisco · USUniversity of Colorado Denver · USUniversity of Pittsburgh · USUniversity of Toronto · CAUniversity of Washington · US

Funding

Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
NIH Prior Approval Process ProfessionalUL1TR002535 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2018 to 2022
$51.1M
University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8M
Institute of Translational Health SciencesUL1TR000423 · NCATS · UNIVERSITY OF WASHINGTON · PI DISIS, MARY L. · 2012 to 2016
$49.4M
Washington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4M
Institutional Clinical and Translational Science AwardUL1TR000003 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2012 to 2015
$38.9M
Childhood Liver Disease Research Network Data Coordinating CenterU01DK062456 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MAGEE, JOHN C, MERION, ROBERT M · 2002 to 2019
$36.8M
Southern California Clinical and Translational Science InstituteUL1TR000130 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BUCHANAN, THOMAS A · 2012 to 2015
$36.0M
Childhood Liver Disease Research Network Data Coordinating CenterU24DK062456 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JOHN C MAGEE · 2019 to 2026
$18.9M
Etiology and Treatment of Biliary Atresia and INHU01DK062453 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI RONALD J. SOKOL · 2002 to 2026
$13.5M
Clinical Center for Cholestatic Liver Disease in ChildrenU01DK062497 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2002 to 2026
$13.2M
VCU-Atlanta Center for the Childhood Liver Disease Research Network (ChiLDReN)U01DK062470 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI SAUL J. KARPEN · 2005 to 2026
$12.7M
NCATS NIH HHS UL1 TR000003NCATS NIH HHS UL1 TR000004NCATS NIH HHS UL1 TR000005NCATS NIH HHS UL1 TR000006NCATS NIH HHS UL1 TR000077NCATS NIH HHS UL1 TR000130NCATS NIH HHS UL1 TR000150NCATS NIH HHS UL1 TR000423NCATS NIH HHS UL1 TR000424NCATS NIH HHS UL1 TR000448NCATS NIH HHS UL1 TR002535NIDDK NIH HHS U01 DK062436NIDDK NIH HHS U01 DK062445NIDDK NIH HHS U01 DK062452NIDDK NIH HHS U01 DK062453NIDDK NIH HHS U01 DK062456NIDDK NIH HHS U01 DK062466NIDDK NIH HHS U01 DK062470NIDDK NIH HHS U01 DK062481NIDDK NIH HHS U01 DK062497NIDDK NIH HHS U01 DK062500NIDDK NIH HHS U01 DK062503NIDDK NIH HHS U01 DK084536NIDDK NIH HHS U01 DK084538NIDDK NIH HHS U01 DK084575NIDDK NIH HHS U01 DK103135NIDDK NIH HHS U01 DK103140NIDDK NIH HHS U01 DK103149NIDDK NIH HHS U24 DK062456
6 · The paper itself

Abstract

backgroundOur objective was to better understand the natural history and disease modifiers of Alpha-1-antitrypsin deficiency (AATD), a common genetic liver disease causing hepatitis and cirrhosis in adults and children. The clinical course is highly variable. Some infants present with neonatal cholestasis, which can resolve spontaneously or progress to cirrhosis; others are well in infancy, only to develop portal hypertension later in childhood.

methodsThe Childhood Liver Disease Research Network has been enrolling AATD participants into longitudinal, observational studies at North American tertiary centers since 2004. We examined the clinical courses of 2 subgroups of participants from the several hundred enrolled; first, those presenting with neonatal cholestasis captured by a unique study, enrolled because of neonatal cholestasis but before specific diagnosis, then followed longitudinally (n=46); second, separately, all participants who progressed to liver transplant (n=119).

resultsWe found male predominance for neonatal cholestasis in AATD (65% male, p=0.04), an association of neonatal gamma-glutamyl transpeptidase elevation to more severe disease, and a higher rate of neonatal cholestasis progression to portal hypertension than previously reported (41%) occurring at median age of 5 months. Participants with and without preceding neonatal cholestasis were at risk of progression to transplant. Participants who progressed to liver transplant following neonatal cholestasis were significantly younger at transplant than those without neonatal cholestasis (4.1 vs. 7.8 years, p=0.04, overall range 0.3-17 years). Neonatal cholestasis had a negative impact on growth parameters. Coagulopathy and varices were common before transplant, but gastrointestinal bleeding was not.

conclusionsPatients with AATD and neonatal cholestasis are at risk of early progression to severe liver disease, but the risk of severe disease extends throughout childhood. Careful attention to nutrition and growth is needed.

Indexed as

alpha 1-Antitrypsin DeficiencyCholestasisHypertension, Portalalpha 1-AntitrypsinChildFemaleHumansInfantInfant, NewbornLiver CirrhosisMalePhenotypealpha 1-Antitrypsin

Identifiers

PMID38055647
PMCPMC10984655
OpenAlexW4389434053

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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.