Prevalence and Determinants of Liver Disease in Relatives of Italian Patients With Advanced MASLD

Year: 2024

Type: article

Abstract: 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.

Source: Clinical Gastroenterology and Hepatology

DOI: 10.1016/j.cgh.2023.12.033

Authors: Serena Pelusi, Luisa Ronzoni, Jessica Rondena, Chiara Rosso, Grazia Pennisi, Paola Dongiovanni, Sara Margarita, Rossana Carpani, Giorgio Soardo, Daniele Prati, Annalisa Cespiati, Salvatore Petta, Elisabetta Bugianesi, Luca Valenti

Institutions: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Turin, University of Palermo, University of Udine, AREA Science Park, Fondazione Italiana Fegato, University of Milan

Language: English

Topic: Liver Disease Diagnosis and Treatment

Subfield: Hepatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,050

Funders: Pfizer, Gilead Sciences, European Federation of Pharmaceutical Industries and Associations, European Commission, Ministero della Salute, Novo Nordisk, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Horizon 2020 Framework Programme, Horizon 2020, H2020 European Research Council, Ministero dell'Istruzione e del Merito

OpenAlex ID: W4390741789