Benaroya Research Institute, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, USA.
Hepatology. 2011 Feb;53(2):448-57. doi: 10.1002/hep.24038. Epub 2010 Nov 29.
Previous studies examining the relationship between hepatic iron deposition and histological severity in nonalcoholic fatty liver disease (NAFLD) have been inconclusive. The goal of this study was to examine the relationship between hepatic iron deposition and liver histology in 849 patients enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Hepatic iron staining was performed in a central laboratory, and the stains were scored for grade and cellular and parenchymal localization by a central pathology committee; the relationship between the grade and pattern of iron deposition and the clinical, laboratory, and histological variables was examined with univariate and multivariate analyses. Stainable hepatic iron was present in 293 of 849 patients (34.5%) in one of three histological patterns: a hepatocellular (HC) pattern [63/849 (7.4%)], a reticuloendothelial system (RES) cell pattern [91/849 (10.7%)], or a mixed RES/HC pattern [139/849 (16.4%)]. Patients with the RES iron-staining pattern were more likely to have advanced fibrosis compared to those with those with HC iron (P = 0.01). Patients with RES iron were also more likely to have advanced histological features such as fibrosis (P = 0.049), portal inflammation (P = 0.002), HC ballooning (P = 0.006), and definite nonalcoholic steatohepatitis (P = 0.007) compared to those with patients with HC or mixed iron patterns. The presence of RES iron (odds ratio = 1.60, 95% confidence interval = 1.10-2.33, P = 0.015) was independently associated with advanced hepatic fibrosis on multiple regression analysis after adjustments for age, gender, diabetes status, and body mass index.
The presence and pattern of hepatic iron deposition are associated with distinct histological features in patients with NAFLD and may have implications for pathophysiology and therapy.
之前研究检查了非酒精性脂肪性肝病(NAFLD)中肝铁沉积与组织学严重程度之间的关系,但结果并不一致。本研究的目的是检查非酒精性脂肪性肝炎临床研究网络中 849 例患者的肝铁沉积与肝组织学之间的关系。在一个中心实验室进行肝铁染色,由一个中心病理学委员会对染色进行分级和细胞及实质定位评分;使用单变量和多变量分析检查铁沉积的分级和模式与临床、实验室和组织学变量之间的关系。在 849 例患者中有 293 例(34.5%)存在三种组织学模式之一的可染色肝铁:肝细胞(HC)模式[849 例中的 63 例(7.4%)]、网状内皮系统(RES)细胞模式[849 例中的 91 例(10.7%)]或混合 RES/HC 模式[849 例中的 139 例(16.4%)]。与具有 HC 铁染色模式的患者相比,具有 RES 铁染色模式的患者更有可能存在晚期纤维化(P=0.01)。与具有 HC 或混合铁模式的患者相比,具有 RES 铁的患者也更有可能具有晚期组织学特征,如纤维化(P=0.049)、门脉炎症(P=0.002)、HC 气球样变(P=0.006)和明确的非酒精性脂肪性肝炎(P=0.007)。多回归分析调整年龄、性别、糖尿病状态和体重指数后,RES 铁的存在(比值比=1.60,95%置信区间=1.10-2.33,P=0.015)与晚期肝纤维化独立相关。
在 NAFLD 患者中,肝铁沉积的存在和模式与不同的组织学特征相关,可能对发病机制和治疗有影响。