Hepatic fibrosis 2022: Unmet needs and a blueprint for the future

Steady progress over four decades toward understanding the pathogenesis and clinical consequences of hepatic fibrosis has led to the expectation of effective antifibrotic drugs, yet none has been approved. Thus, an assessment of the field is timely, to clarify priorities and accelerate progress. Her...

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Published inHepatology (Baltimore, Md.) Vol. 75; no. 2; pp. 473 - 488
Main Authors Friedman, Scott L., Pinzani, Massimo
Format Journal Article
LanguageEnglish
Published United States Wiley Subscription Services, Inc 01.02.2022
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Abstract Steady progress over four decades toward understanding the pathogenesis and clinical consequences of hepatic fibrosis has led to the expectation of effective antifibrotic drugs, yet none has been approved. Thus, an assessment of the field is timely, to clarify priorities and accelerate progress. Here, we highlight the successes to date but, more importantly, identify gaps and unmet needs, both experimentally and clinically. These include the need to better define cell–cell interactions and etiology‐specific elements of fibrogenesis and their link to disease‐specific drivers of portal hypertension. Success in treating viral hepatitis has revealed the remarkable capacity of the liver to degrade scar in reversing fibrosis, yet we know little of the mechanisms underlying this response. Thus, there is an exigent need to clarify the cellular and molecular mechanisms of fibrosis regression in order for therapeutics to mimic the liver’s endogenous capacity. Better refined and more predictive in vitro and animal models will hasten drug development. From a clinical perspective, current diagnostics are improving but not always biologically plausible or sufficiently accurate to supplant biopsy. More urgently, digital pathology methods that leverage machine learning and artificial intelligence must be validated in order to capture more prognostic information from liver biopsies and better quantify the response to therapies. For more refined treatment of NASH, orthogonal approaches that integrate genetic, clinical, and pathological data sets may yield treatments for specific subphenotypes of the disease. Collectively, these and other advances will strengthen and streamline clinical trials and better link histologic responses to clinical outcomes.
AbstractList Steady progress over four decades toward understanding the pathogenesis and clinical consequences of hepatic fibrosis has led to the expectation of effective antifibrotic drugs, yet none has been approved. Thus, an assessment of the field is timely, to clarify priorities and accelerate progress. Here, we highlight the successes to date but, more importantly, identify gaps and unmet needs, both experimentally and clinically. These include the need to better define cell-cell interactions and etiology-specific elements of fibrogenesis and their link to disease-specific drivers of portal hypertension. Success in treating viral hepatitis has revealed the remarkable capacity of the liver to degrade scar in reversing fibrosis, yet we know little of the mechanisms underlying this response. Thus, there is an exigent need to clarify the cellular and molecular mechanisms of fibrosis regression in order for therapeutics to mimic the liver's endogenous capacity. Better refined and more predictive in vitro and animal models will hasten drug development. From a clinical perspective, current diagnostics are improving but not always biologically plausible or sufficiently accurate to supplant biopsy. More urgently, digital pathology methods that leverage machine learning and artificial intelligence must be validated in order to capture more prognostic information from liver biopsies and better quantify the response to therapies. For more refined treatment of NASH, orthogonal approaches that integrate genetic, clinical, and pathological data sets may yield treatments for specific subphenotypes of the disease. Collectively, these and other advances will strengthen and streamline clinical trials and better link histologic responses to clinical outcomes.
Author Friedman, Scott L.
Pinzani, Massimo
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Snippet Steady progress over four decades toward understanding the pathogenesis and clinical consequences of hepatic fibrosis has led to the expectation of effective...
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SubjectTerms Animal models
Animals
Antifibrotic Agents
Artificial intelligence
Biomedical Research
Biopsy
Cell interactions
Clinical trials
Clinical Trials as Topic
Drug Development
Etiology
Fibrosis
Hepatitis
Hepatology
Humans
Learning algorithms
Liver
Liver - diagnostic imaging
Liver - pathology
Liver Cirrhosis - diagnostic imaging
Liver Cirrhosis - drug therapy
Liver Cirrhosis - etiology
Liver Cirrhosis - pathology
Machine learning
Molecular modelling
Needs Assessment
Title Hepatic fibrosis 2022: Unmet needs and a blueprint for the future
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fhep.32285
https://www.ncbi.nlm.nih.gov/pubmed/34923653
https://www.proquest.com/docview/2620214885
Volume 75
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