Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Hum Pathol. 2012 Jun;43(6):790-800. doi: 10.1016/j.humpath.2011.07.007. Epub 2011 Oct 28.
Nonalcoholic fatty liver disease is a global health dilemma. The gold standard for diagnosis is liver biopsy. Ballooned hepatocytes are histologic manifestations of hepatocellular injury and are characteristic of steatohepatitis, the more severe form of nonalcoholic fatty liver disease. Definitive histologic identification of ballooned hepatocytes on routine stains, however, can be difficult. Immunohistochemical evidence for loss of the normal hepatocytic keratin 8/18 can serve as an objective marker of ballooned hepatocytes. We sought to explore the utility of a keratin 8/18 plus ubiquitin double immunohistochemical stain for the histologic evaluation of adult nonalcoholic fatty liver disease. Double immunohistochemical staining for keratin 8/18 and ubiquitin was analyzed using 40 adult human nonalcoholic fatty liver disease core liver biopsies. Ballooned hepatocytes lack keratin 8/18 staining as previously shown by others, but normal-size hepatocytes with keratin loss are approximately 5 times greater in number than keratin-negative ballooned hepatocytes. Keratin-negative ballooned hepatocytes, normal-size hepatocytes with keratin loss, and ubiquitin deposits show a zonal distribution, are positively associated with each other, and are frequently found adjacent to or intermixed with fibrous matrix. All 3 lesions correlate with fibrosis stage and the hematoxylin and eosin diagnosis of steatohepatitis (all P < .05). Compared with hematoxylin and eosin staining, immunohistochemical staining improves the receiver operating characteristics curve for advanced fibrosis (0.77 versus 0.83, 0.89, and 0.89 for keratin-negative ballooned hepatocytes, normal-size hepatocytes with keratin loss, and ubiquitin, respectively) because immunohistochemistry is more sensitive and specific for fibrogenic hepatocellular injury than hematoxylin and eosin staining. Keratin 8/18 plus ubiquitin double immunohistochemical stain improves detection of hepatocyte injury in nonalcoholic fatty liver disease. Thus, it may help differentiate nonalcoholic steatohepatitis from nonalcoholic fatty liver.
非酒精性脂肪性肝病是一个全球性的健康难题。诊断的金标准是肝活检。气球样肝细胞是肝细胞损伤的组织学表现，是更严重的非酒精性脂肪性肝病即脂肪性肝炎的特征。然而，在常规染色上明确诊断气球样肝细胞可能具有一定难度。正常肝细胞角蛋白 8/18 的缺失可以作为气球样肝细胞的客观标志物。我们旨在探讨角蛋白 8/18 和泛素双重免疫组织化学染色在成人非酒精性脂肪性肝病组织学评估中的应用。对 40 例成人非酒精性脂肪性肝病核心肝活检组织进行角蛋白 8/18 和泛素双重免疫组织化学染色分析。气球样肝细胞缺乏角蛋白 8/18 染色，如前所述，但是角蛋白缺失的正常大小肝细胞的数量是角蛋白阴性气球样肝细胞的约 5 倍。角蛋白阴性气球样肝细胞、角蛋白缺失的正常大小肝细胞和泛素沉积呈区域性分布，彼此呈正相关，并且常与纤维基质相邻或混合存在。所有 3 种病变均与纤维化分期和苏木精和伊红（hematoxylin and eosin，H&E）诊断的脂肪性肝炎相关（均 P <.05）。与 H&E 染色相比，免疫组织化学染色提高了对晚期纤维化的受试者工作特征曲线（角蛋白阴性气球样肝细胞、角蛋白缺失的正常大小肝细胞和泛素的曲线下面积分别为 0.77、0.83、0.89 和 0.89），因为免疫组织化学染色比 H&E 染色更敏感和特异于纤维发生的肝细胞损伤。角蛋白 8/18 和泛素双重免疫组织化学染色提高了非酒精性脂肪性肝病中肝细胞损伤的检测。因此，它可能有助于鉴别非酒精性脂肪性肝炎和非酒精性脂肪性肝病。
