背景：根据最近的共识，关于代谢性高铁蛋白血症（MHF）的临床意义的数据有限。我们旨在验证MHF在一般人群和活检证实的代谢功能障碍相关脂肪性肝病（MAFLD）患者中的临床结局。
方法：纳入NHANES数据库和人员队列。MHF定义为具有代谢功能障碍（MD）的血清铁蛋白升高，并根据铁蛋白分为不同等级（1级：200[女性]/300[男性]-550ng/ml；2级：550-1000ng/ml；3级：>1000ng/ml）。临床结果，包括全因死亡,在调整模型中比较了非MHF和MHF的合并症和肝组织学。
结果：在NHANES中，与非MHF和MD相比，MHF与晚期纤维化的高风险相关(FIB-4,P=0.036),白蛋白-肌酐比值升高（UACR，P=0.001)和肌少症(P=0.013)。尽管所有级别的MHF与死亡率之间的关联都是微不足道的（P=0.122），2/3级与死亡率增加相关(P=0.029).与无MD的非MHF相比，MHF的有害影响在死亡率方面更为显著（P<0.001），UACR升高（P<0.001），心血管疾病（P=0.028），和肌肉减少症（P<0.001）。在人员队列中，MHF与更高级的脂肪变性相关（P<0.001），小叶炎症（P<0.001），晚期纤维化（P=0.017），和更严重的肝细胞铁沉积（P<0.001）。
结论：在普通人群和MAFLD高危人群中，MHF与较差的临床结果相关。
BACKGROUND: There is limited data on the clinical significance of metabolic
hyperferritinemia (MHF) based on the most recent
consensus.
OBJECTIVE: We aimed to validate the clinical outcomes of MHF in the general population and patients with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD).
METHODS: The NHANES database and PERSONS cohort were included. MHF was defined as elevated serum ferritin with metabolic dysfunction (MD) and stratified into different grades according to ferritin (grade 1: 200 [females]/300 [males]-550 ng/mL; grade 2: 550-1000 ng/mL; grade 3: >1000 ng/mL). The clinical outcomes, including all-cause death, comorbidities, and liver histology, were compared between non-MHF and MHF in adjusted models.
RESULTS: In NHANES, compared with non-MHF with MD, MHF was related to higher risks of advanced fibrosis (P = .036), elevated albumin-creatinine ratio (UACR, P = .001), and sarcopenia (P = .013). Although the association between all grades of MHF and mortality was insignificant (P = .122), grades 2/3 was associated with increased mortality (P = .029). When comparing with non-MHF without MD, the harmful effects of MHF were more significant in mortality (P < .001), elevated UACR (P < .001), cardiovascular disease (P = .028), and sarcopenia (P < .001). In the PERSONS cohort, MHF was associated with more advanced grades of steatosis (P < .001), lobular inflammation (P < .001), advanced fibrosis (P = .017), and more severe hepatocellular iron deposition (P < .001).
CONCLUSIONS: Both in the general population and in at-risk individuals with MAFLD, MHF was related with poorer clinical outcomes.
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