Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
RexSoft Inc., Seoul, Korea.
Liver Int. 2024 Mar;44(3):799-810. doi: 10.1111/liv.15832. Epub 2024 Jan 17.
BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) encompasses heterogeneous fatty liver diseases associated with metabolic disorders. We aimed to evaluate the association between MAFLD and extrahepatic malignancies based on MAFLD subtypes. METHODS: This nationwide cohort study included 9 298 497 patients who participated in a health-screening programme of the National Health Insurance Service of Korea in 2009. Patients were further classified into four subgroups: non-MAFLD, diabetes mellitus (DM)-MAFLD, overweight/obese-MAFLD and lean-MAFLD. The primary outcome was the development of any primary extrahepatic malignancy, while death, decompensated liver cirrhosis and liver transplantation were considered competing events. The secondary outcomes included all-cause and extrahepatic malignancy-related mortality. RESULTS: In total, 2 500 080 patients were diagnosed with MAFLD. During a median follow-up of 10.3 years, 447 880 patients (6.0%) with extrahepatic malignancies were identified. The DM-MAFLD (adjusted subdistribution hazard ratio [aSHR] = 1.13; 95% confidence interval [CI] = 1.11-1.14; p < .001) and the lean-MAFLD (aSHR = 1.12; 95% CI = 1.10-1.14; p < .001) groups were associated with higher risks of extrahepatic malignancy than the non-MAFLD group. However, the overweight/obese-MAFLD group exhibited a similar risk of extrahepatic malignancy compared to the non-MAFLD group (aSHR = 1.00; 95% CI = .99-1.00; p = .42). These findings were reproduced in several sensitivity analyses. The DM-MAFLD was an independent risk factor for all-cause mortality (adjusted hazard ratio [aHR] = 1.41; 95% CI = 1.40-1.43; p < .001) and extrahepatic malignancy-related mortality (aHR = 1.20; 95% CI = 1.17-1.23; p < .001). CONCLUSION: The diabetic or lean subtype of MAFLD was associated with a higher risk of extrahepatic malignancy than non-MAFLD. As MAFLD comprises a heterogeneous population, appropriate risk stratification and management based on the MAFLD subtypes are required.
背景和目的:代谢相关脂肪性肝病(MAFLD)涵盖了与代谢紊乱相关的多种脂肪性肝病。本研究旨在根据 MAFLD 亚型评估 MAFLD 与肝外恶性肿瘤之间的关联。
方法:这是一项全国性的队列研究,纳入了 2009 年参加韩国国民健康保险服务健康筛查计划的 9298497 名患者。患者进一步分为四组:非 MAFLD、糖尿病合并 MAFLD、超重/肥胖合并 MAFLD 和消瘦合并 MAFLD。主要结局为任何原发性肝外恶性肿瘤的发生,而死亡、失代偿性肝硬化和肝移植则被视为竞争事件。次要结局包括全因和肝外恶性肿瘤相关死亡率。
结果:共有 250 万名患者被诊断为 MAFLD。在中位随访 10.3 年后,共发现 447880 名(6.0%)肝外恶性肿瘤患者。与非 MAFLD 组相比,糖尿病合并 MAFLD 组(调整后的亚分布风险比[aSHR] = 1.13;95%置信区间[CI] = 1.11-1.14;p<0.001)和消瘦合并 MAFLD 组(aSHR = 1.12;95%CI = 1.10-1.14;p<0.001)发生肝外恶性肿瘤的风险更高。然而,超重/肥胖合并 MAFLD 组与非 MAFLD 组发生肝外恶性肿瘤的风险相似(aSHR = 1.00;95%CI = 0.99-1.00;p = 0.42)。这些发现在几项敏感性分析中得到了复制。糖尿病合并 MAFLD 是全因死亡率(调整后的风险比[aHR] = 1.41;95%CI = 1.40-1.43;p<0.001)和肝外恶性肿瘤相关死亡率(aHR = 1.20;95%CI = 1.17-1.23;p<0.001)的独立危险因素。
结论:与非 MAFLD 相比,糖尿病或消瘦型 MAFLD 与肝外恶性肿瘤的风险增加相关。由于 MAFLD 包含一个异质人群,因此需要根据 MAFLD 亚型进行适当的风险分层和管理。
J Formos Med Assoc. 2024-1
J Clin Endocrinol Metab. 2022-1-18
Hepatobiliary Surg Nutr. 2023-10-1