Duseja Ajay, Das Reena, Nanda Mohit, Das Ashim, Garewal Gurjeewan, Chawla Yogesh
Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
World J Gastroenterol. 2005 Jan 21;11(3):393-5. doi: 10.3748/wjg.v11.i3.393.
The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been thought to be one of the triggering factors. Therefore, our aim was to study the role of iron abnormalities and HFE gene mutations in patients with NASH.
Thirty-one patients of NASH diagnosed on the basis of clinical examination biochemistry, ultrasonography and liver biopsy (n = 14) were included in the study. Serum iron parameters (n = 23) (iron, ferritin, total iron-binding capacity and transferrin saturation), Perls' iron staining on liver biopsies (n = 14) and HFE gene mutations (C282Y and H63D) (n = 16) were studied in these patients. The association between iron staining, necroinflammatory activity and fibrosis stage on liver biopsies was also determined.
Elevated serum iron, ferritin and transferrin saturation above 55% were observed in 4.3% of patients. On histology, 71% of the patients had negative iron staining, 21.4% had 1+ staining, 7.2% had 2+ staining and none had 3+ or 4+ staining. There was no association between the degree of iron staining and necroinflammatory activity (P = 0.55) and fibrosis stage (P = 0.09) on histology. None of the patients had C282Y HFE gene mutation and four patients (25%) were found to be heterozygotes for H63D gene mutation.
Our study does not favor iron overload and HFE gene mutations as major factors in the pathogenesis of NASH in Asian Indians.
非酒精性脂肪性肝炎(NASH)患者发生肝脏炎症和纤维化的发病机制尚未完全明确。除胰岛素抵抗外,铁代谢异常被认为是触发因素之一。因此,我们的目的是研究铁代谢异常和HFE基因突变在NASH患者中的作用。
本研究纳入了31例根据临床检查、生化检查、超声检查及肝活检确诊的NASH患者(肝活检患者n = 14)。检测这些患者的血清铁参数(n = 23)(铁、铁蛋白、总铁结合力和转铁蛋白饱和度)、肝活检组织的普鲁士蓝铁染色(n = 14)以及HFE基因突变(C282Y和H63D)(n = 16)。同时还确定了肝活检组织中铁染色、坏死性炎症活动度和纤维化分期之间的相关性。
4.3%的患者血清铁、铁蛋白升高,转铁蛋白饱和度超过55%。组织学检查显示,71%的患者铁染色阴性,21.4%的患者为1+染色,7.2%的患者为2+染色,无患者为3+或4+染色。组织学上,铁染色程度与坏死性炎症活动度(P = 0.55)和纤维化分期(P = 0.09)之间无相关性。所有患者均未检测到C282Y HFE基因突变,4例患者(25%)被发现为H63D基因突变杂合子。
我们的研究不支持铁过载和HFE基因突变是亚洲印度人NASH发病机制中的主要因素。