Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis
Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis
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DOI：
10.1111/j.1572-0241.2001.04052.x
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发表时间：
2001-08-01
影响因子：
9.8
通讯作者：
Fiorelli, G
中科院分区：
文献类型：
--
作者：
Fargion, S;Mattioli, M;Fiorelli, G
目的：探讨高铁蛋白血症和正常转铁蛋白饱和度患者与高铁蛋白血症、铁超载、HFe基因突变、代谢改变和非酒精性脂肪性肝炎(NASH)之间的关系。大多数病例与胰岛素抵抗有关，是持续性高铁蛋白血症的罪魁祸首，并确定了NASH的风险患者。抗饮食限制和正常转铁蛋白饱和度，90例有肝脏脂肪变性的超声证据，60例血色沉着的专性杂合子，均为阴性，无酗酒、肝炎病毒感染和炎症。转铁蛋白饱和度、血清铁蛋白、尿酸、血脂、糖耐量、胰岛素抵抗、HFe基因突变。结果：在40例高铁血症患者中，29例(72%)存在生化代谢异常。26例受检者中有18例(69%)存在胰岛素抵抗，26例(65%)存在两种HFE基因突变之一(正常对照)。33/128[26%]，P<；0.0001)，所有患者的肝铁浓度均升高。31名患者(77%)的组织学符合NASH。在单变量分析中，NASH与代谢改变的存在显著相关。C282Y突变与肝纤维化程度的关系。多因素分析显示，NASH与多种代谢改变共存有关(优势比=5.2，95%CI=0.95~28.7)。当铁蛋白和肝铁浓度较高时，患NASH的风险增大。在90例有肝脏脂肪变性超声征象的患者中，24例(27%)血清铁蛋白升高，转铁蛋白饱和度正常，但仅有6例患者在饮食限制后仍有高铁蛋白血症。结论：转铁蛋白饱和正常的铁蛋白升高在肝脏脂肪变性患者中常见，但它仅反映铁负荷过高，尽管饮食适当但仍持续存在。在大多数与胰岛素抵抗相关的病例中，铁和葡萄糖和/或脂代谢的同时紊乱是持续性高铁素血症的原因，并确定了NASH的风险。
OBJECTIVE: The aim of this study was to define in patients with hyperferritinemia and normal transferrin saturation the relationships among hyperferritinemia, iron overload, HFE gene mutations, the presence of metabolic alterations, and nonalcoholic steatohepatitis (NASH). most of the cases associated with insulin resistance, is responsible for persistent hyperferritinemia and identifies patients at risk for NASH.METHODS: Forty patients with increased serum ferritin. resistant to dietary restriction and normal transferrin saturation, 90 with ultrasonographic evidence of hepatic steatosis, and 60 obligate heterozygotes for hemochromatosis, all negative for alcohol abuse, hepatitis virus infections, and inflammation were studied. Transferrin saturation., serum ferritin, uric acid, lipids, glucose tolerance, insulin resistance, HFE gene mutations. liver histology, and hepatic iron concentration were analyzed.RESULTS: Of the 40 patients with hyperferritinemia, 29 (72%) had biochemical metabolic abnormalities. 18 of the 26 examined (69%) had insulin resistance, 26 (65%) had the presence of one of the two HFE gene mutations (normal controls. 33 of 128 [26%], p < 0.0001), and all had increased liver iron concentration. Thirty-one patients (77%) had histology compatible with NASH. At univariate analysis, NASH was significantly associated with the presence of metabolic alterations. the C282Y mutation, and severity of fibrosis. At multivariate analysis, NASH was associated with the coexistence of multiple metabolic alterations (odds ratio = 5.2, 95% CI = 0.95-28.7). The risk of having NASH augmented in the presence of higher values of ferritin and liver iron concentration. Among the 90 patients with ultrasonographic evidence of hepatic steatosis, 24 (27%) had increased serum ferritin with normal transferrin saturation, but only six remained hyperferritinemic after dietary restriction.CONCLUSION: Increased ferritin with normal transferrin saturation is frequently found in patients with hepatic steatosis, but it reflects iron overload only in those patients in whom it persists despite an appropriate diet. The simultaneous disorder of iron and glucose and/or lipid metabolism, in most of the cases associated with insulin resistance, is responsible for persistent hyperferritinemia and identifies patients at risk for NASH.