The DOI matches its Crossref record; 148 of the 149 references it cites were found in a registry or an index, and 1 are not checked yet.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Histological grading and staging of chronic hepatitis.
Ishak, K., Baptista, A., Bianchi, L., Callea, F., Groote, J. D., Gudat, F., Denk, H., Desmet, V., Korb, G., Macsween, R. N., et al. (1995) · Journal of Hepatology · doi:10.1016/0168-8278(95)80226-6 · Cited by 5,290
Mechanisms of NAFLD development and therapeutic strategies
Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0104-9 · Cited by 4,354
Self-citationAn Algorithm for the Grading of Activity in Chronic Hepatitis C
Bédossa, P., & Poynard, T. (1996) · Hepatology · doi:10.1002/hep.510240201 · Cited by 4,107
Mechanisms of hepatic stellate cell activation
Tsuchida, T., & Friedman, S. L. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.38 · Cited by 2,909
Self-citationMarcellin, P., Gane, E., Buti, M., Afdhal, N., Sievert, W., Jacobson, I. M., Washington, M. K., Germanidis, G., Flaherty, J. F., Schall, R. A., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61425-1 · Cited by 1,788
Resolving the fibrotic niche of human liver cirrhosis at single-cell level
Ramachandran, P., Dobie, R., Wilson-Kanamori, J. R., Dora, E. F., Henderson, B. E. P., Luu, N. T., Portman, J. R., Matchett, K. P., Brice, M., Marwick, J. A., et al. (2019) · Nature · doi:10.1038/s41586-019-1631-3 · Cited by 1,784
Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair
Duffield, J. S., Forbes, S. J., Constandinou, C. M., Clay, S., Partolina, M., Vuthoori, S., Wu, S., Lang, R., & Iredale, J. P. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200522675 · Cited by 1,649
Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations
MacParland, S. A., Liu, J. C., Ma, X.-Z., Innes, B. T., Bartczak, A. M., Gage, B. K., Manuel, J., Khuu, N., Echeverri, J., Linares, I., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06318-7 · Cited by 1,552
Hepatic stellate cells as key target in liver fibrosis
Higashi, T., Friedman, S. L., & Hoshida, Y. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.05.007 · Cited by 1,485
Self-citationLiver Macrophages in Tissue Homeostasis and Disease
Krenkel, O., & Tacke, F. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.11 · Cited by 1,424
Research works printed but not linked: 3
- 1970, Hepatic fibrosis. Correlation of biochemical and morphologic investigations, Am J Med, 49, 707
- 2021, The Tabula Sapiens: a single cell transcriptomic atlas of multiple organs from individual human donors, bioRxiv
- 2020, Why do so many NASH trials fail?, Gastroenterology
Cited by
Sorted by citations
Liver fibrosis in NAFLD/NASH: from pathophysiology towards diagnostic and therapeutic strategies
Parola, M., & Pinzani, M. (2023) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2023.101231 · Cited by 239
Self-citationWang, Y., Hu, J., Wu, S., Fleishman, J. S., Li, Y., Xu, Y.-S., Zou, W., Wang, J., Feng, Y., Chen, J., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01720-0 · Cited by 225
Akkız, H., Gieseler, R. K., & Canbay, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147873 · Cited by 191
The Evolution of Single-Cell RNA Sequencing Technology and Application: Progress and Perspectives
Wang, S., Sun, S.-T., Zhang, X., Ding, H.-R., Yu, Y., He, J., Wang, M.-S., Yang, B., & Li, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032943 · Cited by 183
Mechanisms of organ fibrosis: Emerging concepts and implications for novel treatment strategies
Lurje, I., Gaisa, N. T., Weiskirchen, R., & Tacke, F. (2023) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2023.101191 · Cited by 152
Metadata
- 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 › Hepatology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review