2023-09-08 カロリンスカ研究所(KI)
◆MASLD患者とその関係者に対してライフスタイルの変更を勧め、代謝リスク因子を持つ親戚にはMASLDの早期スクリーニングが役立つ可能性があると指摘されています。MASLDは肝癌の増加要因であり、患者の親戚にも注意が必要です。
<関連情報>
- https://news.ki.se/liver-cancer-and-severe-liver-disease-more-common-if-a-close-relative-has-fatty-liver-disease
- https://www.journal-of-hepatology.eu/article/S0168-8278(23)05071-7/fulltext
MASLDと肝細胞癌の家族性共凝集と有害な肝転帰: 全国規模の多世代コホート研究 Familial Coaggregation of MASLD with Hepatocellular Carcinoma and Adverse Liver Outcomes: Nationwide Multigeneration Cohort Study
Fahim Ebrahimi,Hannes Hagström,Jiangwei Sun,David Bergman,Ying Shang,Wen Yang,Bjorn Roelstraete,Jonas F. Ludvigsson
Journal of Hepatology Published:August 28, 2023
DOI:https://doi.org/10.1016/j.jhep.2023.08.018
Highlights
•Nationwide multigeneration study of 292,274 family members of people with biopsy-confirmed MASLD and comparators.
•MASLD first-degree relatives had increased hazards of HCC, major adverse liver outcomes and liver-related mortality.
•The absolute risk of HCC was low, with only one extra case per 900 first-degree relatives over 20 years of follow-up.
•Spouses of individuals with MASLD also had a higher relative risk of developing major adverse liver outcomes.
•MASLD family members with concomitant chronic liver disease had an accelerated progression of their liver disease.
Abstract
Background & Aims
Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) is the fastest growing cause of hepatocellular carcinoma (HCC) worldwide. However, whether family members of individuals with MASLD also share an increased risk of developing HCC is unknown.
Methods
This nationwide multigeneration cohort-study involved family members of all Swedish adults diagnosed with biopsy-proven MASLD (1969-2017), and matched general population comparators. Using the Swedish Multigeneration Register, we identified 38,018 MASLD first-degree relatives (FDRs: parents, siblings, offspring) and 9,381 MASLD spouses as well as 197,303 comparator FDRs and 47,572 comparator spouses. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) for HCC, major adverse liver outcomes (cirrhosis, decompensated liver disease or liver transplantation), liver-related mortality, extrahepatic cancer, and non-liver-related mortality.
Results
Over a median of 17.6 years, the rate of the primary outcome, HCC was higher in MASLD FDRs vs. comparator FDRs (13 vs. 8/100,000PY; aHR=1.80, 95%CI=1.36-2.37). The HCC risk was further increased in FDRs to individuals with liver fibrosis/cirrhosis (aHR=2.14, 95%CI=1.07-4.27; PHeterogeneity=0.03). MASLD FDRs also had higher rates of major adverse liver outcomes (73 vs. 51/100,000PY; aHR=1.52, 95%CI=1.36-1.69) and liver-related mortality (20 vs. 11/100,000PY; aHR=2.14, 95%CI=1.67-2.74). Individuals with any concomitant chronic liver condition experienced accelerated progression of liver disease when being FDR to an individual with MASLD (aHR=1.47, 95%CI=1.29-1.67). MASLD spouses were at higher risks of major adverse liver outcomes (86 vs. 74/100,000PY; aHR=1.23, 95%CI=1.01-1.51) and liver-related mortality (25 vs. 19/100,000PY; aHR=1.93, 95%CI=1.15-3.23), but not of HCC (aHR=1.43, 95%CI=0.87-2.35).
Conclusions
There is distinct familial clustering of adverse liver-related outcomes in families of individuals with biopsy-proven MASLD with higher relative risks of HCC, progressive liver disease, and liver-related mortality, but absolute risks are low.
Impact and Implications
Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly termed Nonalcoholic fatty liver disease; NAFLD) clusters in families with high genetic susceptibility and shared environmental risk factors, but the risks of developing hepatocellular carcinoma (HCC) and other major liver-related outcomes in family members of individuals with MASLD are largely unknown. This large nationwide multigeneration cohort study involving family members (first-degree relatives and spouses) of individuals with biopsy-proven MASLD and of matched general population comparators found slightly increased risks of HCC in first-degree relatives, and of developing cirrhosis and liver-related mortality in all family members of individuals with biopsy-proven MASLD. The findings of this study provide large-scale evidence to inform clinical practice guidelines for recommendations on the early identification of individuals at higher risk of liver-related morbidity and mortality.
