Hepatic fibrosis 2022: Unmet needs and a blueprint for the future
Open accessAbstract
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.
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Fibrosis and even cirrhosis can regress following successful antiviral therapy in chronic viral hepatitis, immunosuppression in autoimmune hepatitis, or lifestyle modifications and bariatric surgery in metabolic dysfunction-associated steatohepatitis.
“Fibrosis and even cirrhosis can regress, as described following successful antiviral therapy in patients with chronic viral hepatitis, immunosuppression in autoimmune hepatitis, or lifestyle modifications and bariatric surgery in patients with metabolic dysfunction-associated steatohepatitis (MASH) (8–10).”
From Immunoregulation of Liver Fibrosis: New Opportunities for Antifibrotic Therapy (2024) · cites this paper as [8]
Upon removal of the underlying cause, liver fibrosis can resolve via activation of specific immune cell subsets.
“Upon removal of the underlying cause, liver fibrosis can resolve via activation of specific immune cell subsets.”
From Immunoregulation of Liver Fibrosis: New Opportunities for Antifibrotic Therapy (2024) · cites this paper as [8]
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- Authors
- Friedman, S. L., & Pinzani, M.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- University College London (GB)
- Corresponding author
- Friedman, Scott L.
- Pinzani, Massimo
- Venue
- Hepatology
- Published
- 2022-01-11
- Volume
- 75
- Issue
- 2
- Pages
- 473-488
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC12179971
- OpenAlex
- W4200351549
- Cited by
- 430
- References
- 147
- Citations by year
- 2026: 83 · 2025: 76 · 2024: 104 · 2023: 129 · 2022: 37
- FWCI
- 8.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK128289)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Keywords
- liver fibrosis, antifibrotic agents, fibrogenesis, portal hypertension, fibrosis regression, viral hepatitis, liver regeneration, fibrosis diagnosis, liver biopsy, digital pathology, machine learning, artificial intelligence, nonalcoholic steatohepatitis, clinical trials
- MeSH terms
- Drug Development, Antifibrotic Agents, Animals, Clinical Trials as Topic, Fibrosis, Humans, Liver, Liver Cirrhosis, Needs Assessment, Biomedical Research
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