A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Liver Involvement in POLG Disease-a Multicentre Cohort Study of 202 Patients
Tekijät: Kristensen, Erle; Naess, Karin; Engvall, Martin; Klingenberg, Claus; Rasmussen, Magnhild; Brodtkorb, Eylert; Ostergaard, Elsebet; de Coo, Irenaeus; Pias-Peleteiro, Leticia; Isohanni, Pirjo; Uusimaa, Johanna; Majamaa, Kari; Kärppä, Mikko; Martikainen, Mika H.; Ortigoza-Escobar, Juan Dario; Tangeraas, Trine; Berland, Siren; Sue, Carolyn M.; Walker, Judith Sylvia; Harrison, Emma; Biggs, Heather; Horvath, Rita; Darin, Niklas; Rahman, Shamima; Hikmat, Omar
Kustantaja: John Wiley & Sons
Julkaisuvuosi: 2025
Lehti: Journal of Inherited Metabolic Disease
Artikkelin numero: e70112
Vuosikerta: 48
Numero: 6
ISSN: 0141-8955
eISSN: 1573-2665
DOI: https://doi.org/10.1002/jimd.70112
Julkaisun avoimuus kirjaamishetkellä: Ei avoimesti saatavilla
Julkaisukanavan avoimuus : Osittain avoin julkaisukanava
Verkko-osoite: https://onlinelibrary.wiley.com/doi/10.1002/jimd.70112
Liver involvement in POLG disease is common and associated with high morbidity and mortality. Detailed, large-scale, systematic studies of liver involvement are lacking. This study aims to describe the onset, clinical course and prognostic implications of liver involvement in POLG disease. We conducted a multinational, retrospective study including clinical, genetic and biochemical data from patients with confirmed POLG disease. Patients were stratified according to age of disease onset: early-onset (< 12 years), juvenile/adult-onset (12–40 years), and late-onset (> 40 years). Of the 202 patients, 110 (54%) had liver involvement. This could present at any time during the lifespan, but occurred more frequently in patients with early-onset disease (76/98, 78%). Median onset age for liver involvement in females was 7 years (range: 1 month to 50 years), and 21 months in males (birth to 71 years). Infection-triggered disease onset carried a significantly higher risk of liver involvement than spontaneous or other disease triggers. Eighty-five percent of those with liver involvement also had epilepsy. Liver involvement was an indicator of poor prognosis and was significantly associated with worse survival. This study provides a comprehensive description of liver involvement in a large cohort of POLG disease patients. Liver involvement is common in this disease and associated with significantly worse survival. POLG disease should be considered in children presenting with liver involvement, and rapid genetic testing may guide management decisions. Our findings emphasize the need for early vigilance in monitoring liver involvement in all patients with confirmed POLG disease, particularly those with early-onset disease and during intercurrent infection.
Julkaisussa olevat rahoitustiedot:
This study was funded by grants from the Western Norway Regional Health Authority (Helse Vest, grant no. 911944) and by funding from Oslo University Hospital. S.R. acknowledges grant funding from Great Ormond Street Hospital Children's Charity, the Lily Foundation and the National Institute of Health Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre. C.M.S. is supported by NHMRC Practitioner Fellowship 1136800. R.H. is supported by the Wellcome Discovery Award (226653/Z/22/Z), the Medical Research Council (UK) (MR/V009346/1), the Hereditary Neuropathy Foundation, the AFM-Telethon, Ataxia UK, Action for AT, Muscular Dystrophy UK, the Rosetrees Trust (PGL23/100048), the LifeArc Centre to Treat Mitochondrial Diseases (LAC-TreatMito) and the UKRI/Horizon Europe Guarantee MSCA Doctoral Network Programme (Project 101120256: MMM). She is also supported by an MRC strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) MR/ 005021/1. This research was supported by the NIHR Cambridge Biomedical Research Centre (NIHR203312). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
