Evidence map›Paper›PMID 38274490›Full record

ArticleJHEP reports : innovation in hepatology2024

A meta-analysis and real-world cohort study on the sex-related differences in efficacy and safety of immunotherapy for hepatocellular carcinoma.

Lorenz Balcar, Bernhard Scheiner, Claudia Angela Maria Fulgenzi, Antonio D'Alessio, Katharina Pomej, Marta Bofill Roig, Elias Laurin Meyer, Jaekyung Che, Naoshi Nishida, Pei-Chang Lee and 38 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 3 pooled it
4.5field-weighted citation impact, top 4% of its field
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

20 citing papers in PubMed, 3 syntheses or guidelines pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Article
  7. Article
  8. Sex and gender disparities in hepatocellular carcinoma: insights into risk, diagnosis, and therapeutic outcomes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Sex Matters: From Bile Acid Metabolism to Liver Cancer.Cellular and molecular gastroenterology and hepatology · 2024
    Article
  20. 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

48 authors at 20 institutions in 8 countries.

Lorenz BalcarDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Bernhard ScheinerDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Claudia Angela Maria FulgenziDivision of Cancer, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Antonio D'AlessioDivision of Cancer, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Katharina PomejDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Marta Bofill RoigSection for Medical Statistics, Center for Medical Data Science, Medical University of Vienna, Vienna, Austria.
Elias Laurin MeyerSection for Medical Statistics, Center for Medical Data Science, Medical University of Vienna, Vienna, Austria.
Jaekyung CheMedical Oncology, Department of Internal Medicine, CHA Bundang Medical Centre, CHA University, Seongnam, Republic of Korea.
Naoshi NishidaDepartment of Gastroenterology and Hepatology, Kindai University, Faculty of Medicine, Osaka, Japan.
Pei-Chang LeeDivision of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Linda WuDepartment of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY, USA.
Celina AngDepartment of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY, USA.
Anja KrallDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Anwaar SaeedDivision of Hematology/Oncology, Department of Medicine, University of Pittsburgh (UPMC), Pittsburgh, PA, USA.
Bernardo StefaniniDivision of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Antonella CammarotaDrug Development Unit, Sarah Cannon Research Institute UK, London, UK.
Tiziana PressianiMedical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy.
Yehia I AbugabalDept of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Shadi ChamseddineDept of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Brooke WietharnDivision of Medical Oncology, Department of Medicine, University of Kansas Cancer Center, Westwood, KS, USA.
Alessandro ParisiDepartment of Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria delle Marche, Ancona, Italy.
Yi-Hsiang HuangInstitute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan; Healthcare and Services Center, Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.
Samuel PhenDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Caterina VivaldiUnit of Medical Oncology 2, University Hospital of Pisa, Pisa, Italy.
Francesca SalaniDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Gianluca MasiDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Dominik BettingerDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases), Freiburg University Medical Centre, Freiburg, Germany.
Arndt VogelDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Johann von FeldenI. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany.
Kornelius SchulzeI. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany.
Marianna SillettaOperative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200 - 00128 Roma, Italy.
Michael TraunerDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Adel SamsonLeeds Institute of Medical Research at St. James's (LIMR), School of Medicine, Faculty of Medicine and Health, University of Leeds, St James's University Hospital, Leeds, UK.
Henning WegeI. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany.
Fabio PiscagliaDivision of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Peter R GalleI. Medical Department, University Medical Centre Mainz, Mainz, Germany.
Rudolf StauberDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Masatoshi KudoDepartment of Gastroenterology and Hepatology, Kindai University, Faculty of Medicine, Osaka, Japan.
Amit G SingalDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Aleena ItaniStephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Susanna V UlahannanStephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Neehar D ParikhDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Alessio CortelliniDivision of Cancer, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Ahmed KasebDept of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lorenza RimassaDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy.
Hong Jae ChonMedical Oncology, Department of Internal Medicine, CHA Bundang Medical Centre, CHA University, Seongnam, Republic of Korea.
David J PinatoDivision of Cancer, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Matthias PinterDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Medical University of Vienna · ATCampus Bio Medico University Hospital · ITThe University of Texas MD Anderson Cancer Center · USUniversität Hamburg · DEAzienda USL di Bologna · ITCHA University Bundang Medical Center · KRHumanitas University · ITKindai University · JPMedical University of Graz · ATMount Sinai Hospital · USThe University of Texas Southwestern Medical Center · USUniversità degli Studi del Piemonte Orientale “Amedeo Avogadro” · ITUniversity of Oklahoma Health Sciences Center · USUniversity of Pisa · ITAzienda Ospedaliera Universitaria Pisana · ITImperial College London · GBIRCCS Humanitas Research Hospital · ITJohannes Gutenberg University Mainz · DEMarche Polytechnic University · ITMedizinische Hochschule Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background & Aims: Sex-related differences in the immune pathogenesis of hepatocellular carcinoma (HCC), particularly related to oestrogen-dependent secretion of pro-tumourigenic cytokines, are well-known. Whether sex influences the efficacy and safety of immunotherapy is not known. Methods: We performed a restricted maximum likelihood random effects meta-analysis of five phase III trials that evaluated immune checkpoint inhibitors (ICIs) in advanced HCC and reported overall survival (OS) hazard ratios (HRs) stratified by sex to evaluate sex-related differences in OS. In a real-world cohort of 840 patients with HCC from 22 centres included between 2018 and 2023, we directly compared the efficacy and safety of atezolizumab + bevacizumab (A+B) between sexes. Radiological response was reported according to RECIST v1.1. Uni- and multivariable Cox regression analyses were performed for OS and progression-free survival (PFS). Results: In the meta-analysis, immunotherapy was associated with a significant OS benefit only in male (pooled HR 0.79; 95% CI 0.73-0.86) but not in female (pooled HR 0.85; 95% CI 0.70-1.03) patients with HCC. When directly comparing model estimates, no differences in the treatment effect between sexes were observed. Among 840 patients, 677 (81%) were male (mean age 66 ± 11 years), and 163 (19%) were female (mean age 67 ± 12 years). Type and severity of adverse events were similar between the two groups. OS and PFS were comparable between males and females upon uni- and multivariable analyses (aHR for OS and PFS: 0.79, 95% CI 0.59-1.04; 1.02, 95% CI 0.80-1.30, respectively). Objective response rates (24%/22%) and disease control rates (59%/59%) were also similar between sexes. Conclusion: Female phase III trial participants experienced smaller OS benefit following ICI therapy for advanced HCC, while outcomes following A+B treatment were comparable between sexes in a large real-world database. Based on the ambiguous sex-related differences in survival observed here, further investigation of sex-specific clinical and biologic determinants of responsiveness and survival following ICIs are warranted. Impact and implications: While immune checkpoint inhibitors have emerged as standard of care for the treatment of hepatocellular carcinoma, there are conflicting reports on whether the efficacy of cancer immunotherapy differs between females and males. Our study suggests ambiguous sex-related differences in outcomes from immunotherapy in hepatocellular carcinoma. Further investigation of sex-specific clustering in clinicopathologic and immunologic determinants of responsiveness to immune checkpoint inhibitor therapy should be prioritised. Systematic review registration: PROSPERO CRD42023429625.

Indexed as

gendergender medicineimmunotherapyliver cancersex

Identifiers

PMID38274490
PMCPMC10809085
OpenAlexW4389611789

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.