A Population-Based and Clinical Cohort Validation of the Novel Consensus Definition of Metabolic Hyperferritinemia.

CONTEXT: 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). CONCLUSION: Both in the general population and in at-risk individuals with MAFLD, MHF was related with poorer clinical outcomes.

[Effect of zinc on mRNA expression of ZIP4 in Caco2 cells].

OBJECTIVE: To study the effect of zinc on mRNA expression of ZIP4 in human intestinal Caco2 cells and its regularity. METHODS: Low zinc cell model was established by TPEN, a kind of chelating agent which chelates specially to zinc. ZIP4 cDNA fragment was obtained by RT-PCR. Expression of ZIP4 on 10 micromol/L TPEN exposure after 0, 2, 4, 6, 8 and 10 hours in Caco2 cells and its expression on various concentration of TPEN exposure (0,2.5,5,7.5 and 10 micromol/L) was measured by RT-PCR. RESULTS: A proper single fragment is obtained with the sequence conformable to the design. A proper single ZIP4 cDNA fragment was obtained. The mRNA expression of ZIP4 increased in accordance with the duration of low zinc. The peak mRNA level appeared at about 6h. And the ZIP4 mRNA increased in accordance with the concentration of TPEN in Caco2 cells. CONCLUSION: Zinc can regulate the mRNA expression of ZIP4 in Caco2 cells. And ZIP4 may play a role in the absorption of zinc in human intestine.