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Semin Liver Dis 2021; 41(02): 213-224
DOI: 10.1055/s-0041-1725023
Review Article

The Inside-Out of End-Stage Liver Disease: Hepatocytes are the Keystone

Nils Haep‡   *
1   Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
,
Rodrigo M. Florentino‡   *
1   Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
,
James E. Squires
2   Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania
3   Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania
,
Aaron Bell
1   Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
3   Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania
,
Alejandro Soto-Gutierrez
1   Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
3   Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania
› Author Affiliations Financial Disclosure This work was supported by grants from NIH, DK099257, DK117881, DK119973, DK096990, and TR002383 to A.S.-G.
U.S. Department of Health and Human Services
National Institute of Diabetes and Digestive and Kidney Diseases
› Further Information
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Abstract

Chronic liver injury results in cirrhosis and end-stage liver disease (ESLD) which represents a leading cause of death worldwide, affecting people in their most productive years of life. Medical therapy can extend life, but the only definitive treatment is liver transplantation (LT). However, LT remains limited by access to quality donor organs and suboptimal long-term outcomes. The degeneration from healthy-functioning livers to cirrhosis and ESLD involves a dynamic process of hepatocyte damage, diminished hepatic function, and adaptation. However, the mechanisms responsible for deterioration of hepatocyte function and ultimately hepatic failure in man are poorly understood. We review the current understanding of cirrhosis and ESLD as a dynamic process and outline the current mechanisms associated with the development of hepatic failure from the clinical manifestations to energy adaptations, regeneration, and regulation of nuclear transcription factors. A new generation of therapeutics could target stabilization of hepatocyte differentiation and function to avoid the need for transplantation in patients with cirrhosis and ESLD.

Keywords

cirrhosis - terminal liver failure - hepatocyte reprogramming

Competing Interests Statement

A.S.-G. is a co-founder and have a financial interest in Von Baer Wolff, Inc., a company focused on biofabrication of autologous human hepatocytes from stem cells technology and programming liver failure and their interests are managed by the Conflict of Interest Office at the University of Pittsburgh in accordance with their policies.


* These authors contributed equally to this article.




Publication History

Article published online:
15 May 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

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