Ubiquitin as a marker of cell Injury in nonalcoholic steatohepatitis

Ubiquitin as a marker of cell Injury in nonalcoholic steatohepatitis
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DOI:
10.1309/4ubb-bf78-f55v-50ka
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发表时间:
2000-12-01
影响因子:
3.5
通讯作者:
Bonkovsky, HL
Bonkovsky, HL
中科院分区:
医学4区
文献类型:
--
作者:
Banner, BF;Savas, L;Bonkovsky, HL

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泛素(UB)是一种细胞内蛋白质,可与其他蛋白质结合,靶向其进行蛋白水解,与马洛里透明蛋白(MH)相关,支持非酒精性脂肪性肝炎(NASH)的活检诊断。我们分析了来自49例临床诊断为NASH的患者的54份肝活检标本的免疫反应性UB和坏死性炎症、纤维化和普鲁士蓝阳性铁的多种特征,以确定免疫反应性UB的存在是否增加MH的检测或与细胞损伤或HFE基因突变的其他特征相关。对48例患者进行了HFE基因突变分析。活检诊断分布如下:NASH,42例;脂肪变性,10例;非特异性改变,2例。20份标本中存在UB,23份标本中存在MH。在31份0 MH的标本中,6份有UB;在14份1+(可疑)MH的标本中,7份有1+或2+ UB。UB与NASH的诊断和分级、MH的存在、细胞肿胀、小叶炎症和纤维化显著正相关。UB的免疫染色可以增强可疑病例中MH的检测,支持NASH的诊断,并指示哪些患者可能存在疾病进展的风险。
Ubiquitin (UB) an intracellular protein that binds to other proteins to target them for proteolysis, is associated with Mallory hyalin (MH), which supports a biopsy diagnosis of nonalcoholic steatohepatitis (NASH). We analyzed 54 liver biopsy specimens from 49 patients with a clinical diagnosis of NASH for immunoreactive UB and multiple features of necroinflammation, fibrosis, and Prussian blue-positive iron to determine whether the presence of immunoreactive UB increases detection of MH or correlates with other features of cell injury or mutations of the HFE gene. MH and UB were graded Analysis for HFE gene mutations was performed in 48 patients. Biopsy diagnoses were distributed as follows: NASH, 42; steatosis, 10; and nonspecific changes, 2. UB was present in 20 specimens and MH in 23. Of 31 specimens with 0 MH, 6 had UB; of 14 with 1+ (questionable) MH, 7 had 1+ or 2+ UB. UB correlated positively and significantly with the diagnosis and grade of NASH, presence of MH, cell swelling, lobular inflammation, and fibrosis. Immunostaining for UB may enhance detection of MH in questionable cases, support the diagnosis of NASH, and indicate which patients may be at risk for progression of disease.