Hepatocellular organellar abnormalities following elimination of hepatitis C virus

摘要

Abstract Background and aims The 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. Methods The 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. Results Hepatocytes 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 after SVR. Conclusions These results indicate that patients with SVR exhibit a persistent disease state and require long‐term follow‐up to detect early signs of carcinogenesis.