ArticleGastroenterology2022
Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development.
Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02217475 (CENTAUR), which is not on this map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
CENTAUR: Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Subjects With Liver Fibrosis
Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Complexity of metabolic dysfunction-associated steatotic liver disease: State of the art review.Journal of the Chinese Medical Association : JCMA · 2025Review
- Pantothenic acid ameliorates hepatic fibrosis by targeting IGFBP6 to regulate the TGF-β/SMADs pathway.Communications biology · 2025Article
- Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeting senescent hepatocytes for treatment of metabolic dysfunction-associated steatotic liver disease and multi-organ dysfunction.Nature communications · 2025Article
- Phase 3 Validation of PAaM for Hepatocellular Carcinoma Risk Stratification in Cirrhosis.Gastroenterology · 2025Article
- Molecular mechanisms behind the inhibitory effects of ginsenoside Rg3 on hepatic fibrosis: a review.Archives of toxicology · 2025Review
- Stromal vascular fraction inhibits renal fibrosis by regulating metabolism and inflammation in obstructive nephropathy.Frontiers in pharmacology · 2025Article
- An atlas of the human liver diurnal transcriptome and its perturbation by hepatitis C virus infection.Nature communications · 2024Article
- Carfilzomib shows therapeutic potential for reduction of liver fibrosis by targeting hepatic stellate cell activation.Scientific reports · 2024Article
- A revisit of drugs and potential therapeutic targets against non-alcoholic fatty liver disease: learning from clinical trials.Journal of endocrinological investigation · 2024Review
- Epidermal Growth Factor Receptor Inhibition With Erlotinib in Liver: Dose De-Escalation Pilot Trial as an Initial Step in a Chemoprevention Strategy.Gastro hep advances · 2024Article
- Clinico-histological and molecular features of hepatocellular carcinoma from nonalcoholic fatty liver disease.Cancer science · 2023Review
- A thioacetamide-induced liver fibrosis model for pre-clinical studies in microminipig.Scientific reports · 2023Article
- Sample size calculation for a NanoString GeoMx spatial transcriptomics experiment to study predictors of fibrosis progression in non-alcoholic fatty liver disease.Scientific reports · 2023Article
- Inhibition of FGFR2 Signaling by Cynaroside Attenuates Liver Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Macrophage metabolism in nonalcoholic fatty liver disease.Frontiers in immunology · 2023Review
- Hepatocellular Carcinoma Chemoprevention with Generic Agents.Seminars in liver disease · 2022Review
- Current and future colorectal cancer screening strategies.Nature reviews. Gastroenterology & hepatology · 2022Review
- Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease.Science translational medicine · 2022Article
Corrections and comments
- Erratum issuedCorrection.2022
Authors and funding
59 authors at 17 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
aimsThere is a major unmet need to assess the prognostic impact of antifibrotics in clinical trials because of the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression.
methodsA fibrosis progression signature (FPS) was defined to predict fibrosis progression within 5 years in patients with hepatitis C virus and nonalcoholic fatty liver disease (NAFLD) with no to minimal fibrosis at baseline (n = 421) and was validated in an independent NAFLD cohort (n = 78). The FPS was used to assess response to 13 candidate antifibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n = 78) and cenicriviroc in patients with nonalcoholic steatohepatitis enrolled in a clinical trial (n = 19, NCT02217475). A serum protein-based surrogate FPS was developed and tested in a cohort of compensated cirrhosis patients (n = 122).
resultsA 20-gene FPS was defined and validated in an independent NAFLD cohort (adjusted odds ratio, 10.93; area under the receiver operating characteristic curve, 0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacologic target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate antifibrotics identified rational combination therapies based on epigallocatechin gallate, which were validated for enhanced antifibrotic effect in ex vivo culture of clinical liver tissues. In patients with nonalcoholic steatohepatitis treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of the PPARα pathway was absent in patients without fibrosis improvement, suggesting a benefit of combining PPARα agonism to improve the antifibrotic efficacy of cenicriviroc. A 7-protein serum protein-based surrogate FPS was associated with the development of decompensation in cirrhosis patients.
conclusionThe FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform antifibrotic drug development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.