Mak Ki M, Kee Dustin, Cheng Christopher P
Department of Medical Education, Center for Anatomy and Functional Morphology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Anat Rec (Hoboken). 2023 May;306(5):1031-1053. doi: 10.1002/ar.24931. Epub 2022 Apr 21.
This article reviews hepatic fibrosis-associated histopathology of aged cadavers (mean age 82 years). A study of 68 livers identified steatosis in 35.5%, central vein fibrosis in 49.2%, perisinusoidal fibrosis in 63.2%, portal tract fibrosis in 47.7%, septa formation in 44.1%, bridging fibrosis in 30.8%, and cirrhosis in 4.4% of the samples as well as one hepatocellular carcinoma and six metastatic tumors. Other studies have revealed that collagens I, III, IV, V, and VI and fibronectin constitute the matrices of fibrous central veins, perisinusoidal space, portal tracts, and septa. Elastin is rich in portal tracts and fibrous septa but absent from the perisinusoidal space. Hepatic stellate cells are ubiquitous in the liver parenchyma while myofibroblasts localize in fibrotic foci. Factor VIII-related antigen expression signals sinusoidal to systemic vascular endothelium transformation while collagen IV and laminin codistribution indicates formation of perisinusoidal membranes. Their coincidence reflects focalized capillarization of sinusoids in the aged liver. In response to fibrogenesis, hepatic progenitor cells residing in the canal of Hering in the periportal parenchyma undergo expansion and migration deep into the lobule. Concomitantly, intermediate hepatocyte-like cells increase in advanced fibrosis stages, which is possibly related to hepatic regeneration. Metabolic zonation of glutamine synthetase expands from the perivenous to non-perivenous parenchyma in fibrosis progression but its expression is lost in cirrhosis, while cytochrome P-4502E1 expression is maintained in centrilobular and midlobular zones in fibrosis progression and expressed in cirrhosis. Hence, cadaveric livers provide a platform for further investigation of hepatic histopathologies associated with the aging liver.
本文综述了老年尸体（平均年龄82岁）肝脏纤维化相关的组织病理学。一项对68个肝脏的研究发现，35.5%的样本存在脂肪变性，49.2%存在中央静脉纤维化，63.2%存在窦周纤维化，47.7%存在汇管区纤维化，44.1%存在间隔形成，30.8%存在桥接纤维化，4.4%存在肝硬化，还有1例肝细胞癌和6例转移瘤。其他研究表明，I、III、IV、V和VI型胶原以及纤连蛋白构成了纤维性中央静脉、窦周间隙、汇管区和间隔的基质。弹性蛋白在汇管区和纤维间隔中含量丰富，但在窦周间隙中不存在。肝星状细胞在肝实质中普遍存在，而成肌纤维细胞定位于纤维化病灶。VIII因子相关抗原表达信号提示从窦状血管向体循环血管内皮转化，而IV型胶原和层粘连蛋白共分布表明窦周膜形成。它们的同时出现反映了老年肝脏中窦状血管的局灶性毛细血管化。在纤维化过程中，位于门周实质中赫林管的肝祖细胞会发生增殖并向小叶深部迁移。同时，在晚期纤维化阶段，中间型肝细胞样细胞增多，这可能与肝脏再生有关。谷氨酰胺合成酶的代谢分区在纤维化进展过程中从静脉周围实质扩展到非静脉周围实质，但在肝硬化时其表达消失，而细胞色素P - 4502E1在纤维化进展过程中在小叶中央区和中叶区维持表达，并在肝硬化时表达。因此，尸体肝脏为进一步研究与衰老肝脏相关的肝组织病理学提供了一个平台。
