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1. Imaging and histological features of tumor biopsy sample predict aggressive intrasegmental recurrence of hepatocellular carcinoma after radiofrequency ablation

Author

Elia Gigante, Yohann Haddad, Jean-Charles Nault, Olivier Sutter, Einas Abou Ali, Baptiste Bonnet, Gisèle N’Kontchou, Veronique Grando, Nathalie Ganne-Carrié, Pierre Nahon, Lorraine Blaise, Julien Calderaro, Nathalie Barget, Olivier Seror, and Marianne Ziol

Subjects
Medicine, Science
Abstract

Abstract Aggressive intrasegmental recurrence (AIR) is a form of local recurrence associated with a dismal prognosis and defined by multiple nodules or by an infiltrative mass with a tumor thrombus, occurring in the treated segment, after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to identify radiological and/or histological characteristics of tumor biopsy predictive of AIR. We retrospectively analyzed patients treated by No-Touch multi-bipolar RFA (mbpRFA) for a first HCC with a systematic per-procedural tumor biopsy positive for diagnosis of HCC. The first recurrence was classified as non-aggressive local recurrence, AIR or intrahepatic distant recurrence. 212 patients were included (168 men; mean age 67.1 years; mean tumor size 28.6 mm, 181 cirrhosis). AIR occurred in 21/212 patients (10%) and was associated with a higher risk of death (57% in patients with AIR vs 30% without AIR, p = 0.0001). Non-smooth tumor margins, observed in 21% of the patients and macro-trabecular massive histological subtype, observed in 12% of the patients were independently related to a higher risk of AIR (HR: 3.7[1.57;9.06], p = 0.002 and HR:3.8[2.47;10], p = 0.005 respectively). Non smooth margins at imaging and macro-trabecular massive histological subtype are associated with AIR and could be considered as aggressive features useful to stratify therapeutic strategy.

Published
2022
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2. THU-487-YI Upfront multi-bipolar radiofrequency ablation for hepatocarcinoma in transplant-eligible cirrhotic patients with salvage transplantation in case of recurrence

Author

Boros, Carina, Sutter, Olivier, Cauchy, Francois, Ganne-Carrié, Nathalie, Nahon, Pierre, Gisèle, NKontchou, Ziol, Marianne, Lemaire, Véronique Grando, Demory, Alix, Blaise, Lorraine, Dondero, Federica, Durand, Francois, Soubrane, Olivier, Lesurtel, Mickael, Seror, Olivier, and Nault, Jean Charles

Published
2024
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3. THU-459-YI Long-term oncological results of percutaneous radiofrequency ablation for intrahepatic cholangiocarcinoma: a multicentric retrospective study

Author

Alitti, Clémentine, Rode, Agnès, Trillaud, Hervé, Merle, Philippe, Blanc, Jean-Frédéric, Blaise, Lorraine, Demory, Alix, Gisèle, NKontchou, Lemaire, Véronique Grando, Ziol, Marianne, Nahon, Pierre, Ganne-Carrié, Nathalie, Petit, Arthur, Seror, Olivier, Sutter, Olivier, and Nault, Jean Charles

Published
2024
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4. Heterogeneity in adverse events related to atezolizumab-bevacizumab for hepatocellular carcinoma reported in real-world studies

Author

Claudia Campani, Dimitrios Pallas, Sabrina Sidali, Olga Giouleme, Lorraine Blaise, Véronique Grando, Gisele Nkontchou, Alix Demory, Pierre Nahon, Nathalie Ganne-Carrié, and Jean-Charles Nault

Subjects
liver cancer, immunotherapy, adverse effects, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Safety data for patients with hepatocellular carcinoma (HCC) treated with atezolizumab-bevacizumab in the real-world setting remain uncertain. Thus, the aim of this study was to evaluate the incidence of adverse events (AEs) in patients with HCC treated with atezolizumab-bevacizumab in the literature. Methods: In this systematic review and meta-analysis, we searched PubMed for original studies reporting percentages of AEs in patients with HCC receiving atezolizumab-bevacizumab between 2020 to 2023, using the search terms “Atezolizumab/Bevacizumab”, “HCC” and “Adverse events”. We summarized the incidence of AEs and performed a meta-analysis in order to evaluate the incidence of AEs reported in the literature. Results: A total of 30 studies (3,867 patients) were included. The analysis revealed heterogeneity in AE reporting, with arterial hypertension, proteinuria, and fatigue being the most frequently reported AEs whereas incidence of bleeding was reported in 66.7% of the studies and rare immune-related AEs were reported in 26.7% of the studies. The meta-analysis revealed pooled incidence rates of 79% for any grade AEs: 56% for grade 1/2 and 30% for grade ≥3. While the pooled rates of hypertension, anorexia, bleeding, pruritus, rash, and thyroid dysfunction were similar to those reported in the IMbrave150 trial, higher rates were observed in the literature for proteinuria, fatigue, ALT and AST elevations and gastrointestinal perforation. For grade ≥3 AEs, the percentages were consistent with the IMbrave150 trial, except for lower incidences of arterial hypertension and thrombosis in the literature. The exposure-adjusted incidence rates for proteinuria (55.7%), hypertension (45.3%) and fatigue (33.6%) were high. Heterogeneity was observed in the analysis of AEs across articles within the same cohorts of patients. Conclusion: We observed a significant variability in AE reporting for atezolizumab-bevacizumab treatment in HCC in the literature, underscoring the need for standardized reporting practices. Impact and implications: Considering the demonstrated safety of atezolizumab-bevacizumab in randomized-controlled trials, this meta-analysis offers valuable insights into reported occurrences of adverse events. Our study highlights significant heterogeneity among studies, underscoring the need to improve adverse event recording. Understanding the incidence and severity of treatment-related adverse events beyond clinical trials is essential for prompt intervention and may help in preventing treatment discontinuation and complications, potentially leading to better outcomes without significantly compromising quality of life due to adverse events.

Published
2024
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5. Risk factors for hepatocellular carcinoma in patients with alcoholic or viral C cirrhosis

Author

Nathalie Ganne Carrie, Lydie Costentin, Jacques Paries, Myint Tin Tin Htar, Michel Beaugrand, Jean Claude Trinchet, Veronique Grando–Lemaire, and Gisèle N'Kontchou

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Overweight, Gastroenterology, Body Mass Index, Sex Factors, Liver Cirrhosis, Alcoholic, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Aged, Proportional Hazards Models, Univariate analysis, Hepatology, Proportional hazards model, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Liver Neoplasms, Age Factors, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Surgery, Diabetes Mellitus, Type 2, Multivariate Analysis, Female, France, medicine.symptom, business, Body mass index, Follow-Up Studies
Abstract

Background & Aims: Influence of being overweight and diabetes mellitus on the occurrence of hepatocellular carcinoma (HCC) in patients with cirrhosis has not been evaluated prospectively. The aim of this study was to show the predictive value of these factors in a cohort of 771 patients with well-compensated alcohol- or hepatitis C (HCV)-related cirrhosis who were screened prospectively for HCC. Methods: The predictive value for HCC occurrence was assessed by using the log-rank test and the Cox proportional hazards model. At enrollment, the mean age was 61.4 ± 10 years and 431 patients were men. Cirrhosis was caused by alcohol (n = 478), HCV (n = 220), or the association of both factors (n = 73). The mean body mass index (BMI) was 25.4 kg/m2 and 231 patients were diabetic. Results: During a mean follow-up period of 4.2 ± 3 years, 220 patients developed HCC. In univariate analysis, a BMI of 25 kg/m2 or more, diabetes, male sex, age older than 60 years, and HCV infection were risk factors for HCC. In multivariate analysis, predictive factors were a BMI between 25–30 kg/m2 (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.4–2.7), BMI of 30 kg/m2 or more (HR, 2.8; 95% CI, 2.0–4.0), diabetes (HR, 1.6; 95% CI, 1.2–2.1), age 60–70 years (HR, 2.4; 95% CI, 1.3–4.3), age older than 70 years (HR, 3.0; 95% CI, 1.7–5.5), male sex (HR, 2.0; 95% CI, 1.4–2.7), HCV (HR, 1.6; 95% CI, 1.1–2.2), and mixed (HR, 2.6; 95% CI, 1.7–4.0) etiology. We found a positive linear relationship between BMI level and HCC incidence during follow-up evaluation. Conclusions: Overweight and diabetes mellitus are associated with an increased risk of HCC occurrence in patients with HCV- or alcohol-related cirrhosis.

Published
2006

6. Effectiveness of telaprevir or boceprevir in treatment-experienced patients with HCV genotype 1 infection and cirrhosis. : Triple therapy in HCV genotype 1 cirrhotics

Author

Thierry Poynard, Veronique Loustaud Ratti, Dominique Larrey, Isabelle Portal, Patrick Marcellin, Albert Tran, Vincent Di Martino, Patrick Hillon, Jean-Pierre Bronowicki, Isabelle Rosa, Damien Lucidarme, Marc Bourlière, Ghassan Riachi, Christophe Hézode, Pierre Attali, Yoann Barthe, Patrice Cacoub, Olivier Chazouillères, Pierre Bernard, Veronique Grando–Lemaire, Jérôme Gournay, Sophie Metivier, Thong Dao, Stanislas Pol, Jean-Pierre Zarski, Valérie Canva, Victor de Lédinghen, Ventzislava Petrov–Sanchez, Jean-Michel Pawlotsky, Armand Abergel, Laurent Alric, Didier Samuel, Fabrice Carrat, Hélène Fontaine, Jean Jacques Raabe, Céline Dorival, Fabien Zoulim, Xavier Causse, Dominique Guyader, T. Fontanges, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'hépatologie médicale [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Services d'hépatologie, Hospices Civils de Lyon ( HCL ), Service d'hépatologie, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi, Cellules souches normales et cancéreuses, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Service d'hépato-gastro-entérologie, Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Service de médecine interne et maladies digestives, CHU Toulouse [Toulouse], Pharmacochimie et Pharmacologie Pour le Développement ( PHARMA-DEV ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique ( CNRS ), Service d'Hépato-gastro-entérologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département d'hépato-gastroentérologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Centre de recherche biomédicale Bichat-Beaujon ( CRB3 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques ( RESINFIT ), CHU Limoges-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Service d'hépatologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], CHU Etaing, Image Science for Interventional Techniques ( ISIT ), Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Clermont Université-Centre National de la Recherche Scientifique ( CNRS ), Service des maladies du foie, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes], Foie, métabolismes et cancer, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Département digestif, CHU Nice, Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Hépato-gastro-entérologie et oncologie digestive, Centre Hospitalier Régional d'Orléans ( CHR ), Service d'Hépato-Gastro-Enterologie et Nutrition [Caen], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Mobilités : Attention, Orientation et Chronobiologie ( COMETE ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Groupe Hospitalier de l'Institut Catholique Lillois, Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Service de médecine interne [CHU Pitié-Salpétrière], Immunologie - Immunopathologie - Immunothérapeutique ( I3 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôpital Hôtel-Dieu [Paris], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Jean Verdier, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, CH Pierre Oudot Bourgoin-Jallieu, CHI Créteil, Recherches fondamentales, cliniques et thérapeutiques sur les hépatites virales, ANRS, Centre National de Référence Virus des hépatites B, C et Delta, Pôle de Pharmacie - Santé Publique - Information médicale [Saint-Antoine], Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), This study was sponsored and funded by The National Agency for Research on AIDS and Viral Hepatitis (ANRS).The ANRS C020 CUPIC cohort study was conducted with the support and participation of the Association Française pour l'Etude du Foie (AFEF), and CUPIC STUDY GROUP

Subjects
Liver Cirrhosis, Male, Cirrhosis, Comorbidity, Hepacivirus, medicine.disease_cause, Gastroenterology, Polyethylene Glycols, Telaprevir, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Pegylated interferon, boceprevir, Prospective Studies, Treatment Failure, Aged, 80 and over, Middle Aged, Recombinant Proteins, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Oligopeptides, medicine.drug, Adult, medicine.medical_specialty, Genotype, Proline, Hepatitis C virus, Antiviral Agents, 03 medical and health sciences, Boceprevir, Internal medicine, Ribavirin, medicine, chronic hepatitis C, Humans, telaprevir, Adverse effect, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aged, Hepatology, business.industry, cirrhosis, Interferon-alpha, Odds ratio, Hepatitis C, Chronic, medicine.disease, chemistry, Multivariate Analysis, Immunology, business, Follow-Up Studies
Abstract

International audience; BACKGROUND & AIMS: We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis. METHODS: In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.8% partial responders, and 8.0% null responders) were given either telaprevir (n = 299) or boceprevir (n = 212) for 48 weeks. We assessed percentages of patients with sustained viral responses 12 weeks after therapy and safety. This observational study did not allow for direct comparison of the 2 regimens. RESULTS: Among patients given telaprevir, 74.2% of relapsers, 40.0% of partial responders, and 19.4% of null responders achieved SVR12. Among those given boceprevir, 53.9% of relapsers, 38.3% of partial responders, and none of the null responders achieved SVR12. In multivariate analysis, factors associated with SVR12 included prior response to treatment response, no lead-in phase, HCV subtype 1b (vs 1a), and baseline platelet count greater than 100,000/mm(3). Severe adverse events occurred in 49.9% of cases, including liver decompensation, severe infections in 10.4%, and death in 2.2%. In multivariate analysis, baseline serum albumin level less than 35 g/L and baseline platelet counts of 100,000/mm(3) or less predicted severe side effects or death. CONCLUSIONS: Relatively high percentages of real-life, treatment-experienced patients with HCV genotype 1 infection and cirrhosis respond to the combination of peginterferon and ribavirin with telaprevir or boceprevir. However, side effects are frequent and often severe. Baseline levels of albumin and platelet counts can be used to guide treatment decisions. ClinicalTrials.gov number: NCT01514890.

Published
2014
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7. Dynamic of systemic immunity and its impact on tumor recurrence after radiofrequency ablation of hepatocellular carcinoma

Author

Philippe Rochigneux, Jean-Charles Nault, Françoise Mallet, Anne-Sophie Chretien, Nathalie Barget, Alejandro J. Garcia, Lucie Del Pozo, Valérie Bourcier, Lorraine Blaise, Véronique Grando-Lemaire, Gisèle N’Kontchou, Pierre Nahon, Olivier Seror, Marianne Ziol, Nathalie Ganne-Carrié, and Daniel Olive

Subjects
radiofrequency ablation, immune monitoring, innate immunity, nk cells, dendritic cells, pdl1, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Percutaneous radiofrequency ablation (RFA) is one of the main treatments of small hepatocellular carcinoma (HCC). However, it remains unclear whether this local treatment can induce systemic immune variations. Methods: We conducted a prospective study in a tertiary center including consecutive cirrhotic patients with unifocal HCC

Published
2019
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