Department of Experimental Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Pittsburgh Liver Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
Semin Liver Dis. 2023 Nov;43(4):446-459. doi: 10.1055/s-0043-1776760. Epub 2023 Nov 16.
The porphyrias are a group of metabolic disorders that are caused by defects in heme biosynthesis pathway enzymes. The result is accumulation of heme precursors, which can cause neurovisceral and/or cutaneous photosensitivity. Liver is commonly either a source or target of excess porphyrins, and porphyria-associated hepatic dysfunction ranges from minor abnormalities to liver failure. In this review, the first of a three-part series, we describe the defects commonly found in each of the eight enzymes involved in heme biosynthesis. We also discuss the pathophysiology of the hepatic porphyrias in detail, covering epidemiology, histopathology, diagnosis, and complications. Cellular consequences of porphyrin accumulation are discussed, with an emphasis on oxidative stress, protein aggregation, hepatocellular cancer, and endothelial dysfunction. Finally, we review current therapies to treat and manage symptoms of hepatic porphyria.
卟啉症是一组由血红素生物合成途径酶缺陷引起的代谢紊乱。其结果是血红素前体的积累，这可能导致神经内脏和/或皮肤光敏性。肝脏通常是过多卟啉的来源或靶标，与卟啉相关的肝功能障碍从轻微异常到肝衰竭不等。在这篇综述中，我们描述了血红素生物合成中涉及的八种酶中的每一种常见的缺陷。我们还详细讨论了肝性卟啉症的病理生理学，涵盖了流行病学、组织病理学、诊断和并发症。讨论了卟啉积累的细胞后果，重点是氧化应激、蛋白质聚集、肝细胞癌和内皮功能障碍。最后，我们回顾了目前治疗和管理肝性卟啉症症状的方法。
