Abstract

The morphogenesis of lobular restructuring to liver cirrhosis in nonalcoholic steatohepatitis (NASH) is yet to be clearly understood. Therefore, we observed tissue samples from three biopsies and one autopsy with NASH in the non-cirrhotic stage three-dimensionally to elucidate the evolution of fibrosis and the changes of angioarchitecture. Histologic reconstructions revealed that pericellular fibrosis developed around the central vein in the early stage and gradually progressed to arch-shaped band-like fibrosis connecting the central veins in the neighboring lobules. In contrast, the basic angioarchitecture of the portal vein in the portal tracts tended to be preserved in the non-cirrhotic stage, although the portal vein architecture was slightly altered as the portal tract underwent gradual fibrous expansion. In addition, a striking development of arteries originating from the portal tract was found in the fibrotic area around the central and sublobular veins. In summary, while central–central bridging fibrosis and ectopic arterial development were conspicuous, the lobular architecture was maintained relatively well in the non-cirrhotic stage of NASH because of only mildly damaged angioarchitecture of the portal veins. The process of lobular restructuring in NASH is considered to be different from that in chronic viral hepatitis in the non-cirrhotic stage.

Highlights

  • Nonalcoholic steatohepatitis (NASH) is characterized by histological features strikingly similar to those in alcoholic hepatitis [1,2,3,4,5,6,7]

  • There have been many reports on the pathological findings which indicate that NASH leads to liver cirrhosis and occasionally to liver cell carcinoma [13,14,15,16]

  • We observed liver tissues with NASH in the non-cirrhotic stage three-dimensionally, focusing on the evolution of fibrosis and the change of angioarchitecture in connection with lobular restructuring, to answer the question whether these aspects are different in the non-cirrhotic stage of NASH and chronic viral hepatitis

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Summary

Introduction

Nonalcoholic steatohepatitis (NASH) is characterized by histological features strikingly similar to those in alcoholic hepatitis [1,2,3,4,5,6,7]. A grading and staging system for necroinflammatory activity (grade) and fibrosis (stage) for NASH was proposed to assess the histologic features [17, 18]. This system is generally accepted as being reproducible. It has not been fully understood how fibrosis evolves in NASH and results in the development of cirrhosis, in which restructuring of liver lobules is involved. We observed liver tissues with NASH in the non-cirrhotic stage three-dimensionally, focusing on the evolution of fibrosis and the change of angioarchitecture in connection with lobular restructuring, to answer the question whether these aspects are different in the non-cirrhotic stage of NASH and chronic viral hepatitis

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