Evidence map›Paper›PMID 39652104›Full record

ArticleJournal of gastroenterology2025

Serum IL-6 concentration is a useful biomarker to predict the efficacy of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma.

Ryoichi Miura, Atsushi Ono, Hikaru Nakahara, Yuki Shirane, Kenji Yamaoka, Yasutoshi Fujii, Shinsuke Uchikawa, Hatsue Fujino, Eisuke Murakami, Tomokazu Kawaoka and 8 more

Registry-linked trialAbstract read
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In one paragraph

Article in Journal of gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07774247 (A Multicenter, Phase II Study to Evaluate the Safety and Efficacy of Atezolizumab, Bevacizumab, and Tocilizumab in Patients With Advanced Hepatocellular Carcinoma), which is not on this map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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.

NCT07774247 phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

A Multicenter, Phase II Study to Evaluate the Safety and Efficacy of Atezolizumab, Bevacizumab, and Tocilizumab in Patients With Advanced Hepatocellular Carcinoma

TypeinterventionalSponsorCHA UniversityRan2026 to 2029Enrolled51ConditionsHepatocellular Carcinoma (HCC)ArmsAtezolizumab, Bevacizumab, Tocilizumab
3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
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  10. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Ryoichi MiuraDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
Atsushi OnoDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan. atsushi-o@hiroshima-u.ac.jp.ORCID 0000-0002-2482-945X
Hikaru NakaharaDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
Yuki ShiraneDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
Kenji YamaokaDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
Yasutoshi FujiiDepartment of Clinical Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Shinsuke UchikawaDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
Hatsue FujinoDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
Eisuke MurakamiDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
Tomokazu KawaokaDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
Daiki MikiDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
Masataka TsugeDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
Takeshi KishiBiosample Research Center, Radiation Effects Research Foundation, Hiroshima, Japan.
Waka OhishiDepartment of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan.
Naoya SakamotoDepartment of Pathology and Clinical Laboratories, National Cancer Center-Hospital East, Kashiwa, Chiba, Japan.
Koji ArihiroDepartment of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan.
Clair Nelson HayesDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
Shiro OkaDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.

Funding

Bristol Myers Squibb Foundation JP24tm0524006Japan Society for the Promotion of Science London 23K07463Takeda Foundation 2022043779
6 · The paper itself

Abstract

backgroundThis study aims to identify biomarkers for treatment response of atezolizumab plus bevacizumab (Atezo+Bev) in patients with hepatocellular carcinoma (HCC).

methods96 patients who received Atezo+Bev or lenvatinib as a first-line systemic therapy were enrolled as the training group after propensity score matching (PSM), and 42 patients treated with Atezo+Bev were enrolled as the validation group. 17 serum cytokines were measured by Luminex multiplex assay at the start of treatment. For further assessment of the association between cytokine levels and the tumor microenvironment (TME), immunohistochemistry (IHC) was performed on pre-treatment liver biopsy specimens.

resultsIn the derivation set, multivariate analysis identified elevated IL-6 as an independent risk factor in the Atezo+Bev group (HR 5.80: p<0.01), but not in the lenvatinib group; in a subset analysis of patients with low IL-6, PFS was longer in the Atezo+Bev training group than in the lenvatinib group (p = 0.02). A validation study also showed a significantly longer prognosis in the low IL-6 group for both PFS (p = 0.0001) and OS (p = 0.03). Serum IL-6 had a positive correlation with tumor IL-6 expression (ρ = 0.56, p < 0.0001) and an inverse correlation with the CD8/CD163-positive cell count ratio (ρ = -0.4, p < 0.01).

conclusionSerum IL-6 levels are thought to be involved in the suppression of tumor immunity and are useful in predicting the therapeutic effect of Atezo+Bev treatment.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, HepatocellularInterleukin-6Liver NeoplasmsAgedAntibodies, Monoclonal, HumanizedBiomarkers, TumorFemaleHumansMaleMiddle AgedPhenylurea CompoundsPrognosisQuinolinesTreatment OutcomeAntibodies, Monoclonal, HumanizedatezolizumabBevacizumabBiomarkers, TumorIL6 protein, humanInterleukin-6lenvatinibPhenylurea CompoundsQuinolinesAtezolizumab plus bevacizumabInterleukin-6Unresectable hepatocellular carcinoma

Identifiers

PMID39652104
PMCPMC11880141

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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.