Abstract

Children with autoimmune liver disease (AILD) face unique challenges that may impair their health-related quality of life (HRQoL). This multicenter, prospective, longitudinal study evaluated HRQoL over time and identified associated clinical factors.

A total of 162 participants from five centers completed at least one HRQoL assessment. Medical and laboratory data were abstracted within three months of each assessment. Fatigue and pruritus were reported at one center. Generalized linear mixed-effects modeling was used to examine longitudinal associations between HRQoL and clinical variables.

Participants reported the lowest HRQoL scores in school and emotional domains, while the physical and social domains were less affected. Compared to healthy children, participants with AILD reported lower overall HRQoL. Longitudinal analysis revealed that caregivers of participants with overlap syndrome reported higher emotional, social, psychosocial, and total scores. Paradoxically, children with disease complications had better school scores, possibly due to increased support services. Prednisone use was associated with improved emotional scores, while azathioprine use was associated with lower social scores. Elevated ALT levels were associated with lower HRQoL scores, particularly when reported by caregivers. Disease duration and presence of inflammatory bowel disease were not significantly associated with HRQoL.

From one center, fatigue and pruritus were significantly associated with lower HRQoL, especially in the physical, psychosocial, and total domains. Fatigue was also associated with elevated liver enzymes and reduced rates of biochemical remission, suggesting that inflammation may contribute to a disrupted liver-brain axis.

Conclusion These findings underscore the multidimensional impact of AILD on pediatric patients and highlight the need for further research into the pathophysiology of fatigue and potential therapeutic interventions.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by Center for Autoimmune Liver Disease at Cincinnati Children's, NIH P30 DK078392, R01 DK095001

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/IRB of Cincinnati Children's Hospital Medical Center gave ethical approval for this work

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Footnotes

Email: rebecca.farrcchmc.org, cyd.castrorojascchmc.org, mosab.alquraishcchmc.org, kevin.hommelcchmc.org, rashmi.sahay1cchmc.org, alexander.weymannnationwidechildrens.org, katelyn.saarelaseattlechildrens.org, sakil.kulkarniwustl.edu, mary.ayerschp.edu, james.squires2chp.edu, amy.taylorcchmc.org, hkalkwarfgmail.com, alexander.miethkecchmc.org

Data Availability

All data produced in the present work are contained in the manuscript

List of AbbreviationsAILDautoimmune liver diseaseHRQoLhealth-related quality of lifeAIHautoimmune hepatitisPSCprimary sclerosing cholangitisASCautoimmune sclerosing cholangitisCCHMCCincinnati Children’s Hospital Medical CenterA-LiNKAutoimmune Liver disease Network for KidsPedsQL 4.0Pediatric Quality of Life Inventory™ Version 4.0IBDinflammatory bowel diseaseASTaspartate aminotransferaseALTalanine aminotransferaseGGTgamma-glutamyl transpeptidaseIgGimmunoglobulin GINRInternational Normalized RatioAPRIAST to platelet ratio indexFIB-4Fibrosis-4CCTSTCenter for Clinical & Translational Science & TrainingREDCapResearch Electronic Data CaptureMCIDminimal clinically important differenceCLDchronic liver disease