Evidence map›Paper›PMID 41654224›Full record

ArticleJournal of hepatology2026

Serum procalcitonin: A novel tumor biomarker for diagnosis and disease monitoring in fibrolamellar hepatocellular carcinoma.

Jean-Charles Nault, Claudia Campani, Theo Z Hirsch, Ethan Neumann, Waqar Arif, Sandrine Imbeaud, Marina Baretti, Marianne Ziol, Sabrina Sidali, Pauline Roger and 18 more

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Article in Journal of hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors.

Jean-Charles NaultCentre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm, F-75006, Paris, France; APHP, Hôpital Avicenne, Liver Unit, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Université Paris Sorbonne Nord Bobigny, France. Electronic address: naultjc@gmail.com.
Claudia CampaniCentre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm, F-75006, Paris, France; Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Florence, Italy.
Theo Z HirschCentre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm, F-75006, Paris, France.
Ethan NeumannJohns Hopkins Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Johns Hopkins Bloomberg Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Waqar ArifJohns Hopkins Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Johns Hopkins Bloomberg Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Sandrine ImbeaudCentre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm, F-75006, Paris, France.
Marina BarettiJohns Hopkins Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Johns Hopkins Bloomberg Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Marianne ZiolCentre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm, F-75006, Paris, France; AP-HP, Hôpital Avicenne, Service d'Anatomopathologie, Bobigny, 93000, France.
Sabrina SidaliCentre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm, F-75006, Paris, France.
Pauline RogerCentre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm, F-75006, Paris, France.
Manon AllaireAP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France; INSERM UMR 1138, Centre de recherche des Cordeliers, Paris, 75006, France.
Mohamed BouattourDepartment of Liver Cancer and Innovative Therapy Unit, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, AP-HP. Nord, Clichy, France Université Paris Cité, Centre de Recherche Sur L'Inflammation (CRI), INSERM, U1149, CNRS, Paris, France.
Fabio MarraDepartment of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Florence, Italy.
Brice FresneauDepartment of Children and Adolescents Oncology, Gustave Roussy, Villejuif, France; INSERM U1018 CESP, Radiation Epidemiology Team, Paris-Saclay University, Gustave Roussy Cancer Campus, Villejuif, France.
Neus LlarchBarcelona Clinic Liver Cancer (BCLC) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain Liver Oncology Unit, Liver Unit, ICMDM Hospital Clinic de Barcelona, Barcelona, Spain Universitat de Barcelona, Barcelona, Spain.
Jean-Marie PeronDepartment of Hepatogastroenterology, Rangueil University Hospital, 31059 Toulouse, France.
René GerolamiIHU Méditerranée Infection, Marseille, France, MEPHI, Aix-Marseille Université, Marseille, France; Unité hépatologie, Hôpital de la Timone, Marseille, France, Assistance Publique-Hôpitaux de Marseille (APHM), Marseille, France.
Eric Nguyen KhacHepato-Gastroenterology Department, CHU Amiens, Amiens, France.
Pierre NahonCentre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm, F-75006, Paris, France; APHP, Hôpital Avicenne, Liver Unit, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Université Paris Sorbonne Nord Bobigny, France.
Nathalie Ganne-CarriéCentre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm, F-75006, Paris, France; APHP, Hôpital Avicenne, Liver Unit, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Université Paris Sorbonne Nord Bobigny, France.
Julien CaldéraroDepartment of Pathology, Henri-Mondor Hospital, MINT-Hep, Mondor Integrative Hepatology Assistance Publique-Hôpitaux Paris (AP-HP), Créteil, France; INSERM, U955, Créteil, France; Université Paris-Est Créteil (UPEC), Créteil, France.
Aurélie BeaufrèreUniversité Paris Cité, Centre de Recherche Sur L'Inflammation (CRI), INSERM, U1149, Paris, France; AP-HP.Nord, Department of Pathology, FHU MOSAIC, SIRIC InsiTu, DMU DREAM, Beaujon Hospital, 100 Boulevard du Général Leclerc, 92110, Clichy, France.
Valérie ParadisUniversité Paris Cité, Centre de Recherche Sur L'Inflammation (CRI), INSERM, U1149, Paris, France; AP-HP.Nord, Department of Pathology, FHU MOSAIC, SIRIC InsiTu, DMU DREAM, Beaujon Hospital, 100 Boulevard du Général Leclerc, 92110, Clichy, France.
Catherine GuettierService d'anatomie pathologique, hôpitaux Bicêtre-Paul Brousse-Béclère, 78, rue du Général-Leclerc, 94270 Le Kremlin-Bicêtre, France Faculté de médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
CAPRIH FFCD cohort
Angela SuttonAP-HP, HUPSSD, Avicenne Hospital, Sorbonne Paris Nord University, Biochemistry Department, 93000 Bobigny, France; Hypoxie et Poumon, Inserm U1272, Université Sorbonne Paris Nord, 93000 Bobigny, France.
Mark YarchoanJohns Hopkins Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Johns Hopkins Bloomberg Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Jessica Zucman-RossiCentre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm, F-75006, Paris, France; Department of Oncology, Assistance Publique-Hôpitaux Paris (AP-HP), HEGP Institut du Cancer Paris CARPEM, Paris, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsFibrolamellar carcinoma (FLC) is a rare primary liver cancer that predominantly affects young patients with normal known serum tumor biomarkers. An observation of elevated procalcitonin (PCT) in one patient prompted us to investigate PCT as a biomarker in a larger FLC cohort.

methodsWe measured serum PCT levels in 34 samples from 18 patients with FLC and in 64 patients with hepatocellular carcinoma (HCC), 24 with cholangiocarcinoma (CCA), and 20 with cirrhosis. Using RNA sequencing, we analyzed expression of CALCA, which encodes PCT, in 27 FLC tumors, 331 HCC tumors, 39 CCA tumors, 71 hepatoblastomas, 34 hepatocellular adenomas, and 55 non-tumor liver samples. Spatial transcriptomics was performed on three FLC tumors, and PCT immunohistochemistry was performed on 13 FLC tumors and 34 other primary or secondary liver cancers.

resultsIn eight patients with FLC from the European cohort, median serum PCT was significantly elevated (55.2 μg/L) compared to patients with HCC (0.14 μg/L), CCA (0.16 μg/L), and cirrhosis (0.11 μg/L; p = 0.0005). These findings were validated in a US cohort of 10 patients with FLC compared to HCC and CCA (p = 0.0002). Across these cohorts, elevated serum PCT was observed in 83% of FLC cases vs. 3% of HCC and CCA cases (p <0.0001). In four patients, changes in serum PCT levels correlated with radiologic response according to RECIST 1.1. RNA sequencing demonstrated significant overexpression of CALCA in FLC compared to other primary liver tumors (p <0.0001), and spatial transcriptomics localized CALCA expression specifically to tumor cells. Immunohistochemistry confirmed PCT overexpression in 77% of FLC tumors but not in other liver cancers.

conclusionProcalcitonin is a sensitive and specific serum biomarker for FLC among primary liver cancers, with potential utility for diagnosis and monitoring of treatment response. IMPACT AND IMPLICATIONS: This study is justified by the lack of reliable serum biomarkers for fibrolamellar carcinoma (FLC) and demonstrates that procalcitonin is specifically overexpressed by FLC tumor cells and detectable in the blood of the patients with FLC. These findings are important for clinicians and researchers, as they identify a readily available biomarker that may facilitate diagnosis, improve disease monitoring, and support clinical trial design in a rare cancer that predominantly affects young patients. In clinical practice, serum PCT measurement could be incorporated as a non-invasive adjunct to imaging for the diagnosis and longitudinal assessment of FLC, although prospective studies in larger and more diverse cohorts are needed to refine diagnostic cut-offs and confirm specificity.

Indexed as

Biomarkers, TumorCarcinoma, HepatocellularLiver NeoplasmsProcalcitoninAdultAgedCalcitoninCholangiocarcinomaFemaleHumansMaleMiddle AgedBiomarkers, TumorCalcitoninProcalcitoninbiomarkerCALCAdiagnosisfibrolamellar carcinomahepatocellular carcinomaimmunotherapyprocalcitoninprognosisserum

Identifiers

PMID41654224

What OpenQuestion holds

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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.