Evidence map›Paper›PMID 42758714›Full record

ArticlePloS one2026

Divergent effects of semaglutide and CRV431 Co-therapy on liver fibrosis and HCC in MASLD mouse model.

Asha Z Goodman, Winston T Stauffer, Philippe A Gallay

Abstract read
In one paragraph

Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Asha Z GoodmanDepartment of Immunology & Microbiology, Scripps Research, La Jolla, California, United States of America.ORCID https://orcid.org/0000-0001-9015-4844
Winston T StaufferDepartment of Immunology & Microbiology, Scripps Research, La Jolla, California, United States of America.
Philippe A GallayDepartment of Immunology & Microbiology, Scripps Research, La Jolla, California, United States of America.

Funding

Non-immunosuppressive Sanglifehrin Analogs as Therapeutic Agents for Viral Hepatitis-induced Liver Damage DevelopmentR01AI143931 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI GALLAY, PHILIPPE ANDRE · 2020 to 2024
$2.2M
NIAID NIH HHS R01 AI143931
6 · The paper itself

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by progressive fibrosis and an increased risk of hepatocellular carcinoma (HCC). Recently, approved drug treatments for MASLD, including thyroid hormone receptor beta (THR-β) and glucagon-like peptide-1 (GLP-1) receptor agonists, have been effective in treating the underlying metabolic causes of MASLD. However, more effective and acute treatments, particularly for already advanced or cirrhotic steatohepatitis, remain elusive. Other drug candidates, such as cyclophilin inhibitors, which have shown promise for treating advanced MASLD, are still under investigation. Because advanced MASLD reflects both upstream metabolic stress and downstream, self-sustaining injury responses promoting inflammation and fibrogenesis, we investigated whether pairing GLP-1 agonism (metabolic correction) with cyclophilin inhibition (fibrosis and inflammation remodeling) would yield additive or emergent benefits. Thus, we evaluated Semaglutide, Rencofilstat (CRV431), and their co-administration in a C57BL/6J model of diet- and toxin-induced MASLD via a Western diet, sucrose supplementation, and chronic carbon tetrachloride exposure. Semaglutide monotherapy significantly reduced body weight and decreased HCC burden (Kruskal-Wallis Analysis, p < 0.0001) whereas fibrosis quantified by picrosirius red staining did not differ significantly across the treatment groups (Welch's Analysis of Variance, p = 0.1725). Co-therapy did not improve collagen deposition compared with monotherapy. These findings indicate that the combination of GLP-1 receptor agonism with cyclophilin inhibition does not confer additive antifibrotic benefits in this advanced MASLD model, underscoring stage-dependent constraints on therapeutic synergy.

Indexed as

Carcinoma, HepatocellularCyclosporineGlucagon-Like PeptidesLiver CirrhosisLiver NeoplasmsNon-alcoholic Fatty Liver DiseaseAnimalsDisease Models, AnimalDrug Therapy, CombinationMaleMiceMice, Inbred C57BLSemaglutideCyclosporineGlucagon-Like PeptidesSemaglutide

Identifiers

PMID42758714
PMCPMC13588371

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.