Prevalence and determinants of liver disease in relatives of Italian patients with advanced MASLD
Open accessAbstract
BACKGROUND & AIMS: Metabolic dysfunction associated steatotic liver disease (MASLD) has a strong genetic component. The aim of this study was to examine noninvasively the prevalence of MASLD and of advanced fibrosis in relatives of patients with advanced MASLD and the risk factors for liver involvement, with a focus on the contribution of common genetic risk variants. METHODS: We prospectively enrolled 98 consecutive probands with advanced fibrosis and/or hepatocellular carcinoma caused by MASLD and 160 nontwin first-degree relatives noninvasively screened for MASLD and advanced fibrosis at 4 Italian centers. We evaluated common genetic determinants and polygenic risk scores of liver disease. RESULTS: Among relatives, prevalence of MASLD was 56.8% overall, whereas advanced fibrosis was observed in 14.4%. At multivariable analysis in relatives, MASLD was associated with body mass index (odds ratio [OR], 1.31 [1.18-1.46]) and tended to be associated with diabetes (OR, 5.21 [0.97-28.10]), alcohol intake (OR, 1.32 [0.98-1.78]), and with female sex (OR, 0.54 [0.23-1.15]), whereas advanced fibrosis was associated with diabetes (OR, 3.13 [1.16-8.45]) and nearly with body mass index (OR, 1.09 [1.00-1.19]). Despite that the PNPLA3 risk variant was enriched in probands (P = .003) and overtransmitted to relatives with MASLD (P = .045), evaluation of genetic risk variants and polygenic risk scores was not useful to guide noninvasive screening of advanced fibrosis in relatives. CONCLUSIONS: We confirmed that about 1 in 7 relatives of patients with advanced MASLD has advanced fibrosis, supporting clinical recommendations to perform family screening in this setting. Genetic risk variants contributed to liver disease within families but did not meaningfully improve fibrosis risk stratification.
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Initial data suggest that individuals with strong family history, early disease onset, or lack of accruing factors may benefit from a comprehensive genetic evaluation that may identify strong genetic determinants of SLD with potential implications for treatment and family counselling.
“Initial data suggest that individuals with a) strong family history, b) early disease onset, or c) lack of accruing factors may bene fi t from a comprehensive genetic evaluation ( e.g. whole-exome sequencing or targeted panel sequencing) that may identify strong genetic determinants of SLD with potential implications for treatment and family counselling. 135,208 -211”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [211]
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References 30 · Cited by 16
Research works printed but not linked: 6
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- Authors
- Pelusi, S., Ronzoni, L., Rondena, J., Rosso, C., Pennisi, G., Dongiovanni, P., Margarita, S., Carpani, R., Soardo, G., Prati, D., Cespiati, A., Petta, S., Bugianesi, E., & Valenti, L.
- Affiliations
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- University of Turin (IT)
- University of Palermo (IT)
- University of Udine (IT)
- University of Milan (IT)
- Corresponding author
- Valenti, Luca
- ORCID
- Venue
- Clinical Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2024-11
- Volume
- 22
- Issue
- 11
- Pages
- 2231-2239.e4
- ISSN
- 1542-3565 (ISSN-L)
- OpenAlex
- W4390741789
- Cited by
- 16
- References
- 30
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Gastroenterology and Hepatology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Funders
- Ministero dell'Istruzione dell'Universita e della Ricerca
- European Commission (PE00000019 CUP B73C22001250006, RF-2021-12372399, H2020-ICT-2018-20/H2020-ICT-2020-2, IN-IT-989-5790, HORIZON-MISS-2021-CANCER-02-03)
- Horizon 2020
- Ministero della Salute (RF-2016-02364358, PR-0361, PNRR-MAD-2022-12375656, RF-2021-12373889)
- ERC (101016726, 101096312, 777377)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- non-alcoholic fatty liver disease, advanced liver fibrosis, hepatocellular carcinoma, family screening, first-degree relatives, genetic risk variants, PNPLA3, polygenic risk score, diabetes mellitus, body mass index, alcohol consumption, sex differences
- MeSH terms
- Adult, Aged, Family, Fatty Liver, Female, Humans, Italy, Lipase, Liver Cirrhosis, Male, Membrane Proteins, Middle Aged, Prospective Studies, Risk Factors, Prevalence, Genetic Predisposition to Disease
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