Evidence map›Paper›PMID 39949265›Full record

ArticleAlimentary pharmacology & therapeutics2025

Clinical Trial to Assess the Safety and Tolerability of Anti-IL 23 Monoclonal Antibody Guselkumab in Patients With Alcohol-Associated Liver Disease.

Luis Antonio Diaz, Sheldon Morris, Shravan Dave, Susy M Kim, Wathnita Sarik, Lisa Richards, Egbert Madamba, Ricki Bettencourt, Christian Fulinara, Thuy Pham and 9 more

Abstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Alimentary pharmacology & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. [Alcohol liver disease: immunoregulatory mechanisms and precision therapeutic targets].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
    Review
  2. Review
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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

19 authors.

Luis Antonio DiazMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.ORCID https://orcid.org/0000-0002-8540-4930
Sheldon MorrisMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.
Shravan DaveMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.ORCID https://orcid.org/0000-0002-2875-4926
Susy M KimMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.
Wathnita SarikMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.
Lisa RichardsMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.
Egbert MadambaMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.
Ricki BettencourtMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.
Christian FulinaraAlpha Clinic, University of California San Diego, San Diego, California, USA.
Thuy PhamAlpha Clinic, University of California San Diego, San Diego, California, USA.
Grant MillerDepartment of Medicine, University of California San Diego School of Medicine, San Diego, California, USA.
Raquel Carvalho-Gontijo WeberDepartment of Medicine, University of California San Diego School of Medicine, San Diego, California, USA.
Jeremiah D MomperMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.
Feng HeBiostatistics Research Center, School of Public Health, University of California, San Diego, California, USA.
Sonia JainBiostatistics Research Center, School of Public Health, University of California, San Diego, California, USA.ORCID https://orcid.org/0000-0001-8408-1247
Catriona JamiesonMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.
Tatiana KisselevaMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.
David BrennerMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.
Rohit LoombaMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA.ORCID https://orcid.org/0000-0002-4845-9991

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
Yeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2000 to 2022
$69.8M
The Southernearch Center for ALPD and CirrhosisP50AA011999 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ANNA S. GUKOVSKAYA · 1999 to 2026
$45.8M
Tissue-specific roles of FXR in CVD and NASHP01HL147835 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EVANS, RONALD M · 2020 to 2024
$12.2M
San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8M
Transcriptional co-regulators and macrophage gene expressionR01DK091183 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLASS, CHRISTOPHER K · 2011 to 2025
$9.9M
Inactivation of Hepatic Stellate Cells During Reversal of Liver FibrosisR01DK099205 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRENNER, DAVID A., KISSELEVA, TATIANA · 2014 to 2025
$4.8M
The Role of Portal Fibroblasts in Cholestatic Liver FibrosisR01DK101737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA · 2014 to 2025
$3.8M
Novel IL-23 inhibitor for the treatment of alcohol associated liver diseaseU01AA029019 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA, LOOMBA, ROHIT · 2020 to 2024
$3.7M
The role of IL-17 signaling in alcohol-induced HCCR01AA028550 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRENNER, DAVID A., KISSELEVA, TATIANA · 2021 to 2025
$2.3M
Collagen fibers and fragments regulate pancreatic cancer metabolism and growth.R01CA285997 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DAVID A. BRENNER, Michael Karin · 2024 to 2026
$2.2M
Development and validation of a novel 3D human in vitro model of nonalcoholic steatohepatitis to be used for novel therapeutic screening and research on disease mechanism.R44DK115242 · NIDDK · ORGANOVO, INC. · PI MINER, JEFFREY N. · 2017 to 2019
$1.7M
California HIV/AIDS Research ProgramCalifornia Institute for Regenerative MedicineJohn C Martin Foundation RP124NCATS NIH HHS 5UL1TR001442NCATS NIH HHS UL1 TR001442NCI NIH HHS R01 CA285997NHLBI NIH HHS P01 HL147835NHLBI NIH HHS P01HL147835NIAAA NIH HHS P50 AA011999NIAAA NIH HHS R01 AA028550NIAAA NIH HHS U01 AA029019NIAAA NIH HHS U01AA029019NIDDK NIH HHS P30 DK120515NIDDK NIH HHS P30DK120515NIDDK NIH HHS R01 DK091183NIDDK NIH HHS R01 DK099205NIDDK NIH HHS R01 DK101737NIDDK NIH HHS R01 DK111866NIDDK NIH HHS R44 DK115242NIDDK NIH HHS R56 DK088837NIEHS NIH HHS P42 ES010337NIH HHS AA011999NIH HHS AA028550NIH HHS DK091183NIH HHS DK099205NIH HHS DK101737NIH HHS DK120515NIH HHS P42ES010337NIH HHS R01CA285997NIH HHS R01DK111866NIH HHS R44DK115242NIH HHS R56DK088837Sanford Stem Cell Fitness and Space Medicine CenterVisby Medical Inc
6 · The paper itself

Abstract

backgroundThere are no FDA-approved therapies for alcohol-associated liver disease (ALD). Preclinical studies indicate that blocking IL-23/IL-17 signalling may reverse liver injury. Guselkumab, an IL-23-specific antibody approved for psoriasis, may be beneficial for ALD.

aimsWe aimed to assess the safety and tolerability of guselkumab in patients with ALD.

methodsThis phase-1 dose-escalation study included patients with ≥ 2 DSM-5 criteria for alcohol use disorder, significant steatosis (MRI-PDFF ≥ 8%) and MRE < 3.63 kPa (to exclude advanced disease). Guselkumab was given subcutaneously on Days 1 and 29 in 30, 70 or 100 mg dose cohorts. Primary endpoints were adverse events (AEs) and dose-limiting toxicity.

resultsWe enrolled 13 patients (three 30 mg, three 70 mg, and seven 100 mg). Eleven completed the study and two early discontinued in the 100 mg group. Of them, 77% were men, and the median age was 53 [IQR 49-61] years. The median MRI-PDFF and MRE were 18.4% [IQR 8.4%-34.0%] and 2.5 [2.2-2.6] kPa, respectively. The most frequent AEs were hyperuricemia (13%, mild only) and elevated lipase (11%, mild and moderate). There were no serious adverse events or significant variations in liver enzymes. There was a suppression of peripheral interleukin (IL)-17, IL-23, IL-1b and TNF-α in the 70 and 100 mg groups, and a significant decrease in alcohol consumption over time (AUDIT-C: 6 [3-7] vs. 5 [1-6], p = 0.023).

conclusionsGuselkumab is safe in doses up to 100 mg and may reduce inflammation markers in ALD. These findings support further phase 2 studies to evaluate the efficacy of guselkumab in ALD, particularly in patients with severe phenotypes.

Indexed as

Antibodies, MonoclonalInterleukin-23Liver Diseases, AlcoholicAntibodies, Monoclonal, HumanizedDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedTreatment OutcomeAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedguselkumabInterleukin-23alcoholic cirrhosisalcohol‐related liver diseaseALDcirrhosisliver diseasesteatotic liver disease

Identifiers

PMID39949265
PMCPMC12087978

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Registered trials

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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.