Evidence map›Paper›PMID 42061924›Full record

ArticleJHEP reports : innovation in hepatology2026

Multicenter study of bleeding and thromboembolic events with durvalumab tremelimumab vs. atezolizumab and bevacizumab in advanced HCC.

Najib Ben Khaled, Raphael Mohr, Leonie S Jochheim, Valentina Zarka, Monika Karin, Fabian Artusa, Julia M Schütte, Vera Himmelsbach, Ursula Ehmer, Katrin Böttcher and 21 more

Abstract readMulticenter StudyComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2026. 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. Review
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

31 authors.

Najib Ben KhaledDepartment of Medicine II, University Hospital, LMU Munich, Munich, Germany(†)(,)(‡).
Raphael MohrDepartment of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Berlin, Germany(†).
Leonie S JochheimDepartment of Gastroenterology, Hepatology and Transplant Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Valentina ZarkaDivision of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany(†)(,)(‡).
Monika KarinDepartment of Medicine II, University Hospital, LMU Munich, Munich, Germany(†)(,)(‡).
Fabian ArtusaDepartment of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Berlin, Germany(†).
Julia M SchütteDepartment of Gastroenterology, Hepatology and Transplant Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Vera HimmelsbachDepartment of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Frankfurt/Main, Germany(†).
Ursula EhmerTUM School of Medicine and Health, Department for Internal Medicine II, TUM University Hospital, Technical University of Munich, Munich, Germany (†)(,)(‡).
Katrin BöttcherTUM School of Medicine and Health, Department for Internal Medicine II, TUM University Hospital, Technical University of Munich, Munich, Germany (†)(,)(‡); Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany(†); M3 Research Center, University Hospital Tübingen, University of Tübingen, Tübingen, Germany(†).
Friedrich FoersterDepartment of Medicine I, University Medical Center of the Johannes-Gutenberg University Mainz, Germany(†).
Simon Johannes GairingDepartment of Medicine I, University Medical Center of the Johannes-Gutenberg University Mainz, Germany(†).
Paula BarkDepartment of Medicine I, University Medical Center of the Johannes-Gutenberg University Mainz, Germany(†).
Alexander WeichDivision of Gastroenterology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany(‡).
Ignazio PisedduDepartment of Medicine II, University Hospital, LMU Munich, Munich, Germany(†)(,)(‡).
Monika RauDivision of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany(†)(,)(‡).
Bernhard ScheinerDivision of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria(†).
Lorenz BalcarDivision of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria(†).
Marino VeneritoDepartment of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital Magdeburg, Magdeburg, Germany.
Philipp HeumannGastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany(‡).
Arne KandulskiGastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany(‡).
Catherine LeyhDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Düsseldorf, Germany(†).
Christoph RoderburgDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Düsseldorf, Germany(†).
Tom LüddeDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Düsseldorf, Germany(†).
Matthias PinterDivision of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria(†).
Julia MayerleDepartment of Medicine II, University Hospital, LMU Munich, Munich, Germany(†)(,)(‡).
Jens U MarquardtDepartment of Medicine I, University Medical Center, Lübeck, Germany(†).
Fabian FinkelmeierDepartment of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Frankfurt/Main, Germany(†).
Enrico N De ToniDepartment of Medicine II, University Hospital, LMU Munich, Munich, Germany(†)(,)(‡).
Andreas GeierDivision of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany(†)(,)(‡).
Florian P ReiterDivision of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany(†)(,)(‡). Electronic address: Reiter_F@ukw.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsAtezolizumab/bevacizumab (A/B) and durvalumab ± tremelimumab (DT/D) are preferred first-line regimens for the treatment of hepatocellular carcinoma (HCC). Although both therapies share an anti-PD-L1-backbone, only the A/B-combination is targeting vascular-endothelial-growth-factor (VEGF). This difference may have safety-implications, as the anti-VEGF component may elevate the risk of bleeding and thromboembolic events. This multicenter study analyzes bleeding or thromboembolic events in patients receiving therapy with DT/D, compared with A/B.

methodsPatients with HCC treated with A/B exclusively before the approval of DT/D, or treated with DT/D, were recruited from 11 tertiary centers and analyzed retrospectively. Information on baseline characteristics was collected. Kaplan-Meier analyses and multivariate Cox regression modeling was used to compare event rates.

resultsThis study included 490 patients (n = 165 DT/D; n = 325 A/B). The DT/D group showed a higher prevalence of gastroesophageal varices and increased spleen size. Median follow-up time was similar in both groups. A total of 74 patients (22.8%) treated with A/B showed a bleeding event of any grade vs. 22 patients (13.3%) treated with DT/D (p = 0.016). High-grade ≥3 bleeding episodes were more frequent in the A/B group with 47 patients (14.5%) vs. 12 patients (7.3%) in the DT/D group (p = 0.027). Kaplan-Meier analysis showed significantly shorter time to first bleeding (p = 0.037) with A/B as compared with DT/D. Multivariate regression confirmed that treatment with A/B was independently associated with an increased bleeding risk (p = 0.010). Variceal bleeding and thromboembolic events did not differ significantly between both groups.

conclusionsOverall and high-grade bleeding events were more frequent and occurred earlier in patients treated with A/B vs. DT/D, whereas variceal bleeding, grade 4-5 bleeding, and thromboembolic events did not differ significantly between groups. These findings should be confirmed in randomized trials or, if not feasible, through meta-analyses to provide more robust evidence for treatment decisions in advanced HCC. IMPACT AND IMPLICATIONS: This multicenter retrospective study was scientifically justified by the need to clarify whether the addition of VEGF inhibition to PD-L1-based immunotherapy confers differential bleeding or thromboembolic risks in patients with advanced HCC. The results are particularly relevant for clinicians and trialists, as they demonstrate a higher incidence and earlier onset of overall and high-grade bleeding events with atezolizumab/bevacizumab compared with durvalumab ± tremelimumab, despite similar rates of variceal bleeding and thromboembolic events. These findings may inform treatment selection, risk stratification, and surveillance strategies in routine practice, especially in patients with portal hypertension or other bleeding risk factors. Given the retrospective design and baseline-imbalances between treatment groups, the results should be interpreted cautiously and warrant confirmation in prospective randomized studies or, if not feasible, through meta-analyses.

Indexed as

Antineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, HepatocellularHemorrhageLiver NeoplasmsThromboembolismAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedFemaleHumansMaleMiddle AgedRetrospective StudiesAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalatezolizumabBevacizumabdurvalumabtremelimumabBleeding riskHepatocellular carcinomaImmunotherapyThromboembolic eventsVEGF inhibitors

Identifiers

PMID42061924
PMCPMC13141955

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