Evolving therapies for liver fibrosis
Detlef Schuppan,Yong Ook Kim +1 more
TLDR
This work focuses on antifibrotic approaches for liver that address specific cell types and functional units that orchestrate fibrotic wound healing responses and have a sound preclinical database or antifIBrotic activity in early clinical trials.Abstract:
Fibrosis is an intrinsic response to chronic injury, maintaining organ integrity when extensive necrosis or apoptosis occurs. With protracted damage, fibrosis can progress toward excessive scarring and organ failure, as in liver cirrhosis. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development, with enormous potential but also high risks. Preclinical research has yielded numerous targets for antifibrotic agents, some of which have entered early-phase clinical studies, but progress has been hampered due to the relative lack of sensitive and specific biomarkers to measure fibrosis progression or reversal. Here we focus on antifibrotic approaches for liver that address specific cell types and functional units that orchestrate fibrotic wound healing responses and have a sound preclinical database or antifibrotic activity in early clinical trials. We also touch upon relevant clinical study endpoints, optimal study design, and developments in fibrosis imaging and biomarkers.read more
Citations
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Journal ArticleDOI
Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology
Ingmar Mederacke,Christine C. Hsu,Juliane S. Troeger,Peter Huebener,Xueru Mu,Dianne H. Dapito,Jean-Philippe Pradere,Robert F. Schwabe +7 more
TL;DR: It is demonstrated that hepatic stellate cells give rise to 82-96% of myofibroblasts in models of toxic, cholestatic and fatty liver disease, and HSCs should be considered the primary cellular target for anti-fibrotic therapies across all types of liver disease.
Journal ArticleDOI
Macrophage heterogeneity in liver injury and fibrosis
TL;DR: Hepatic macrophages are central in the pathogenesis of chronic liver injury and have been proposed as potential targets in combatting fibrosis, and understanding the mechanisms that regulate hepaticmacrophage heterogeneity may help to develop novel macrophage subset-targeted therapies for Liver injury and fibrosis.
Journal ArticleDOI
Pathobiology of liver fibrosis: a translational success story
TL;DR: The past three decades of steady progress in understanding liver fibrosis have contributed to an emerging translational success story, with realistic hopes for antifibrotic therapies to treat patients with chronic liver disease in the near future.
Journal ArticleDOI
Hepatic stellate cells in liver development, regeneration, and cancer
TL;DR: Recent advances in understanding of the formation and characteristics of hepatic stellate cells, as well as their function in liver development, regeneration, and cancer are summarized and evaluated.
Journal ArticleDOI
Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance
TL;DR: The clinical relevance of celldeath, focusing on biomarkers; the contribution of cell death to drug-induced, viral, and fatty liver disease and liver cancer; and evidence for cell death pathways as therapeutic targets are reviewed.
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