Familial coaggregation of MASLD with hepatocellular carcinoma and adverse liver outcomes: Nationwide multigenerational cohort study

• DOI: 10.1016/j.jhep.2023.08.018
• Publication Date: 2023-08-28T16:09:15Z
• Authors: Fahim Ebrahimi; Hannes Hagström; Jiangwei Sun; David Bergman; Ying Shang; Wen Yang; Bjorn Roelstraete; Jonas F. Ludvigsson
• Keywords: Liver disease; First-degree relatives; Liver Cancer

•Nationwide multigenerational study of 292,274 family members people with biopsy-confirmed MASLD and comparators.•MASLD first-degree relatives had increased hazards HCC, major adverse liver outcomes liver-related mortality.•The absolute risk HCC was low, only one extra case per 900 over 20 years follow-up.•Spouses individuals also a higher relative developing outcomes.•Liver disease progressed more rapidly in concomitant diseases. Background & AimsMetabolic dysfunction-associated steatotic (MASLD; formerly NAFLD) is the fastest growing cause hepatocellular carcinoma (HCC) worldwide. However, whether share an unknown.MethodsThis nationwide cohort involved all Swedish adults diagnosed biopsy-proven (1969−2017), matched general population comparators. Using Multi-generation Register, we identified 38,018 (FDRs: parents, siblings, offspring) 9,381 spouses patients MASLD, as well 197,303 comparator FDRs 47,572 spouses. We used Cox proportional models to calculate adjusted hazard ratios (aHRs) for (cirrhosis, decompensated or transplantation), mortality, extrahepatic cancer, non-liver-related mortality.ResultsOver median 17.6 years, rate primary outcome vs. (13 8/100,000 person-years [PY]; aHR 1.80, 95% CI 1.36−2.37). The further fibrosis/cirrhosis (aHR 2.14, 1.07−4.27; PHeterogeneity = 0.03). rates (73 51/100,000 PY; 1.52, 1.36−1.69) mortality (20 11/100,000 1.67−2.74). any chronic condition experienced accelerated progression 1.47, 1.29-1.67). were at risks (86 74/100,000 1.23, 1.01−1.51) (25 19/100,000 1.93, 1.15−3.23), but not 1.43, 0.87−2.35).ConclusionsThere distinct familial clustering families progressive disease, are low.Impact implicationsMetabolic termed clusters high genetic susceptibility shared environmental factors, other largely unknown. This large involving (first-degree spouses) comparators found slightly relatives, cirrhosis MASLD. findings this provide large-scale evidence inform clinical practice guidelines recommendations on early identification morbidity mortality. Metabolic Over 0.87−2.35). There low.