Evidence map›Paper›PMID 40778804›Full record

ArticleLiver international : official journal of the International Association for the Study of the Liver2025

High Grade Hepatotoxicity From Dual Checkpoint Inhibitors Is More Common in Hepatocellular Carcinoma Than Other Cancers.

Elsie Ennin, Niharika Mallepally, Myra Ali, Layla Shojaie, Sean Dewberry, Melissa Trieu, Evanthia T Roussos Torres, Kali Zhou, Jeffrey Kahn, Jennifer L Dodge and 1 more

Abstract read
In one paragraph

Article in Liver international : official journal of the International Association for the Study of the Liver, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

11 authors.

Elsie EnninDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.ORCID 0009-0001-0089-2075
Niharika MallepallyDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Myra AliDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Layla ShojaieDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Sean DewberryDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Melissa TrieuDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Evanthia T Roussos TorresDivision of Hematology and Oncology, Norris Comprehensive Cancer Center, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Kali ZhouDivision of Gastrointestinal and Liver Diseases, Research Center for Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.ORCID 0000-0001-8554-2906
Jeffrey KahnDivision of Gastrointestinal and Liver Diseases, Research Center for Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.ORCID 0000-0001-8618-4776
Jennifer L DodgeDivision of Gastrointestinal and Liver Diseases, Research Center for Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Lily DaraDivision of Gastrointestinal and Liver Diseases, Research Center for Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Funding

Southern California Clinical and Translational Science InstituteUL1TR001855 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Thomas A Buchanan, Michele D. Kipke · 2016 to 2026
$81.3M
Targeting Cell Death Pathways in Immune-mediated Liver Injury from Checkpoint InhibitorsR03DK132437 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DARA, LILY · 2022 to 2023
$248k
NCATS NIH HHS UL1 TR001855NCATS NIH HHS UL1TR001855NIDDK NIH HHS R03 DK132437NIDDK NIH HHS R03DK132437
6 · The paper itself

Abstract

BACKGROUND &

aimsImmune checkpoint inhibitors (ICIs) are therapy for many malignancies including hepatocellular carcinoma (HCC), yet the impact of HCC on immune-mediated liver injury from checkpoint inhibitors (ILICI) remains poorly understood and no direct comparison exists for hepatotoxicity rates between ICI and sorafenib in HCC.

methodsIn this retrospective cohort study, we extracted data on adult patients treated with five ICI regimens for HCC or non-HCC cancers, and HCC patients who received sorafenib between 2010 and 2020. The primary outcome was grade ≥ 3 ILICI or sorafenib (DILI). Logistic regression estimated adjusted odds ratios (OR) for liver injury.

resultsWe identified 530 patients, 129 (24%) HCC-ICI, 256 (48%) non-HCC ICI, and 145 (27%) HCC-sorafenib. Compared to non-HCC ICI, HCC-ICI and HCC-sorafenib were more often male (57%, 82%, 77%), Hispanic (14%, 35%, 34%), and cirrhotic (1%, 85%, 88%). Twenty-three patients developed grade ≥ 3 ILICI. ILICI incidence was higher for HCC-ICI (11%, CI 6-18) versus non-HCC ICI (4%, CI 2-6, p = 0.006) and DILI in HCC-sorafenib (3%, CI 1-8, p = 0.02) with incidence highest for ipilimumab-nivolumab (HCC-ICI 42%, CI 15-72 versus non-HCC 10%, CI 3-24; p = 0.02). On multivariable regression, ILICI was associated with HCC (OR 4.5, CI 1.8-11.4, p = 0.002) and treatment with ipilimumab-nivolumab (OR 6.9, CI 2.6-18.3, p < 0.001). Incidence of liver injury in HCC remained elevated for ICI versus sorafenib (OR 3.5, CI 1.2-10.4, p = 0.02).

conclusionsWe identified an elevated risk of liver injury in HCC patients receiving ICIs compared to ICI-treated non-HCC cancers and sorafenib-treated HCC, with dual ipilimumab-nivolumab therapy carrying the highest risk.

Indexed as

Carcinoma, HepatocellularChemical and Drug Induced Liver InjuryImmune Checkpoint InhibitorsLiver NeoplasmsSorafenibAdultAgedFemaleHumansIncidenceLogistic ModelsMaleMiddle AgedRetrospective StudiesImmune Checkpoint InhibitorsSorafenibCTLA‐4ILICIimmune‐related adverse eventsimmunotherapyliver injuryPD‐1

Identifiers

PMID40778804
PMCPMC12345591

What Socratic holds

Textmetadata
LicenceTDM
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.