Kogiso Tomomi, Ogasawara Yuri, Taniai Makiko, Tokushige Katsutoshi, Nakai Yousuke
Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Japan.
Japan Community Health Care Organization Tokyo Joto Hospital, Koto-ku, Japan.
Hepatol Res. 2025 Jul 1. doi: 10.1111/hepr.14233.
The Delphi consensus established new criteria for steatotic liver disease (SLD), but the extrahepatic complications in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. In this study, we investigated the clinical course of MASLD patients compared to those with MASLD and increased alcohol intake (MetALD) and alcohol-associated liver disease (ALD).
A total of 1150 Asian patients with SLD were enrolled and categorized into the MASLD (n = 803), MetALD (n = 81), and ALD (n = 266) groups. The incidence levels of extrahepatic malignancies and cardiovascular disease (CVD) events were compared among the three groups. Genetic alterations in PNPLA3, HSD17B13, GCKR, and GDF15 were analyzed in 201 MASLD cases.
MASLD patients were significantly younger (MASLD, MetALD, ALD; 53, 65, and 62 years), had a lower proportion of males (49.3%, 82.7%, and 86.8%), and had a higher BMI (26.7, 24.1, and 22.6 kg/m) than MetALD and ALD patients. During a median follow-up of 10.6 years, the proportions of patients who developed extrahepatic malignancies were 7.2%, 9.9%, and 5.6%, and those who experienced CVD events were 5.7%, 3.7%, and 4.1% in the MASLD, MetALD, and ALD groups, respectively. However, Cox proportional hazards analysis revealed no significant difference in the risk of extrahepatic complications among the groups after adjusting for baseline characteristics. A single nucleotide polymorphism in PNPLA3 was associated with the development of CVD events in MASLD patients.
Extrahepatic events were observed at similar rates among patients with SLD after adjusting for confounding factors. However, overall mortality and the risk of HCC were significantly higher in the MetALD and ALD groups.
德尔菲共识制定了脂肪性肝病（SLD）的新标准，但代谢功能障碍相关脂肪性肝病（MASLD）患者的肝外并发症仍不明确。在本研究中，我们调查了MASLD患者与合并酒精摄入增加的MASLD患者（代谢性酒精性脂肪性肝病[MetALD]）及酒精性肝病（ALD）患者相比的临床病程。
共纳入1150例亚洲SLD患者，并将其分为MASLD组（n = 803）、MetALD组（n = 81）和ALD组（n = 266）。比较三组肝外恶性肿瘤和心血管疾病（CVD）事件的发生率。对201例MASLD病例分析了PNPLA3、HSD17B13、GCKR和GDF15的基因改变。
与MetALD和ALD患者相比，MASLD患者明显更年轻（MASLD、MetALD、ALD分别为53岁、65岁和62岁），男性比例更低（分别为49.3%、82.7%和86.8%），BMI更高（分别为26.7、24.1和22.6kg/m²）。在中位随访10.6年期间，MASLD、MetALD和ALD组发生肝外恶性肿瘤的患者比例分别为7.2%、9.9%和5.6%，发生CVD事件的患者比例分别为5.7%、3.7%和4.1%。然而，Cox比例风险分析显示，在调整基线特征后，各组肝外并发症风险无显著差异。PNPLA3中的一个单核苷酸多态性与MASLD患者CVD事件的发生有关。
在调整混杂因素后，SLD患者肝外事件的发生率相似。然而，MetALD和ALD组的总体死亡率和肝细胞癌风险显著更高。
