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Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
Targeting liver fibrosis: strategies for development and validation of antifibrotic therapies
1Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Abstract:
We have made striking progress in our understanding of the biochemistry and cell biology that underlies liver fibrosis and cirrhosis, including the development of strategies and agents to prevent and reverse fibrosis. However, translation of this knowledge into clinical practice has been hampered by (1) the limitation of many in vitro and in vivo models to confirm mechanisms and to test antifibrotic agents, and (2) the lack of sensitive methodologies to quantify the degree of liver fibrosis and the dynamics of fibrosis progression or reversal in patients. Furthermore, whereas cirrhosis and subsequent decompensation are accepted hard clinical endpoints, fibrosis and fibrosis progression alone are merely plausible surrogates for future clinical deterioration. In this review we focus on an optimized strategy for preclinical antifibrotic drug development and highlight the current and future techniques that permit noninvasive assessment and quantification of liver fibrosis and fibrogenesis. The availability of such noninvasive methodologies will serve as the pacemaker for the clinical development and validation of potent antifibrotic agents.
Insights
Developing noninvasive methods to track liver fibrosis is crucial for advancing antifibrotic drug development and clinical validation. This progress aids in understanding and treating liver fibrosis and cirrhosis.
Area of Science:
- Hepatology and Translational Medicine
- Biochemistry and Cell Biology of Liver Disease
Background:
- Significant advancements in understanding liver fibrosis and cirrhosis biochemistry and cell biology.
- Clinical translation of antifibrotic strategies is limited by inadequate preclinical models and lack of sensitive patient assessment tools.
Purpose of the Study:
- To review optimized strategies for preclinical antifibrotic drug development.
- To highlight current and future techniques for noninvasive assessment and quantification of liver fibrosis and fibrogenesis.
Main Methods:
- Focus on preclinical antifibrotic drug development strategies.
- Review of existing and emerging noninvasive techniques for liver fibrosis assessment.
Main Results:
- Limitations in current in vitro and in vivo models hinder mechanism confirmation and agent testing.
- Lack of sensitive methodologies impedes quantification of fibrosis degree and dynamics in patients.
Conclusions:
- Noninvasive methodologies are essential for accelerating the clinical development and validation of effective antifibrotic agents.
- Improved assessment tools will bridge the gap between laboratory findings and clinical application in managing liver fibrosis and cirrhosis.
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