Hepatocellular organellar abnormalities following elimination of hepatitis C virus
Hepatocellular organellar abnormalities following elimination of hepatitis C virus
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DOI：
10.1111/liv.15624
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发表时间：
2023-06-13
影响因子：
6.7
通讯作者：
Aizaki，Hideki
中科院分区：
文献类型：
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作者：
Aoyagi，Haruyo;Iijima，Hiroko;Aizaki，Hideki
背景和目的持续病毒学应答（SVR）后肝细胞癌（HCC）的未来发展是一个重要的问题。本研究的目的是探讨SVR患者肝细胞器的病理改变，并描述细胞器异常可能与SVR后癌变有关。和SVR进行了比较，细胞和小鼠模型和半定量评估使用透射电子显微镜。细胞核、线粒体、内质网、脂滴和细胞周纤维化的异常，与丙型肝炎病毒（HCV）感染的小鼠和细胞中观察到的异常相当。DAA治疗显着减少细胞器异常，如细胞核，线粒体和脂质滴在患者和小鼠的肝细胞后SVR，治愈细胞，但它没有改变扩张/脱颗粒内质网和细胞周围纤维化的患者和小鼠后SVR。此外，来自SVR后>1年的患者的样本在线粒体和内质网中的异常数量显著多于<1年的患者。SVR后患者细胞器异常的可能原因可能是与纤维化引起的血管系统异常相关的内质网和线粒体的氧化应激。有趣的是，异常内质网与肝癌患者SVR后>1年相关。结论这些结果表明，SVR患者表现出持续的疾病状态，需要长期随访，以检测早期癌变迹象。
Background and aimsThe future development of hepatocellular carcinoma (HCC) in patients after sustained virologic response (SVR) is an important issue. The purposes of this study were to investigate pathological alterations in organelle of the liver of SVR patients and to characterize organelle abnormalities that may be related to carcinogenesis after SVR.MethodsThe ultrastructure of liver biopsy specimens from patients with chronic hepatitis C (CHC) and SVR were compared to cell and mouse models and assessed semi‐quantitatively using transmission electron microscopy.ResultsHepatocytes in patients with CHC showed abnormalities in the nucleus, mitochondria, endoplasmic reticulum, lipid droplet, and pericellular fibrosis, comparable to those seen in hepatitis C virus (HCV)‐infected mice and cells. DAA treatment significantly reduced organelle abnormalities such as the nucleus, mitochondria, and lipid droplet in the hepatocytes of patients and mice after SVR, and cured cells, but it did not change dilated/degranulated endoplasmic reticulum and pericellular fibrosis in patients and mice after SVR. Further, samples from patients with a post‐SVR period of >1 year had significantly larger numbers of abnormalities in the mitochondria and endoplasmic reticulum than those of <1 year. A possible cause of organelle abnormalities in patients after SVR could be oxidative stress of the endoplasmic reticulum and mitochondria associated with abnormalities of the vascular system due to fibrosis. Interestingly, abnormal endoplasmic reticulum was associated with patients with HCC for >1 year after SVR.ConclusionsThese results indicate that patients with SVR exhibit a persistent disease state and require long‐term follow‐up to detect early signs of carcinogenesis.