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1. 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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2. Patient and physician expectations regarding disease and treatment of advanced HCC: The prospective PERCEPTION1 study

Author: Jean-Charles Nault, Nanthara Sritharan, Gontran Verset, Ivan Borbath, Marie Lequoy, Manon Allaire, Hélène Regnault, Isabelle Colle, Hans Orlent, Isabelle Sinapi, Christophe Moreno, Edouard Larrey, Sabrina Sidali, Clémence Hollande, Giuliana Amaddeo, Stanislas Pol, Pierre Nahon, Nathalie Ganne-Carrié, Vincent Levy, Coralie Bloch-Queyrat, Eric Trepo, and Mohammed Bouattour
Subjects: hepatocellular carcinoma, systemic treatment, immunotherapy, perception, life expectancy, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: We aimed to explore patient expectations regarding their treatments and prognosis in comparison to physicians' assessments in patients with advanced hepatocellular carcinoma (HCC) receiving systemic treatments. Methods: We prospectively enrolled 205 patients in France and Belgium with Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC receiving systemic treatment (NCT04823754). Patients completed a 28-question survey and the hospital anxiety and depression scale (HADS), while physicians filled a 17-question survey after the initial consultation. Univariate and multivariate models were used to assess factors associated with concordant patient-physician responses, HADS, as well as predicted (by physicians) and observed overall survival. Results: Patients had a median age of 68 years with 75% having BCLC C HCC; 86.3% received atezolizumab/bevacizumab. 60% of patients did not discuss life expectancy with the physician. 63% of the patients believed they had a life expectancy >5 years. Among shared questions between patients and physicians, 36.4% concordance was observed; major differences centered on life expectancy with patients more optimistic than physicians. A lower patient-physician concordance was seen with shorter-consultations (p = 0.003), female physicians (p = 0.02), BCLC C (p = 0.03) and >100 HCC patients/year per physician (p = 0.008). Compared to France, patients from Belgium were more likely to be satisfied with the consultation (p
Published: 2024
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3. MASLD-related HCC: Multicenter study comparing patients with and without cirrhosis

Author: Carole Vitellius, Elvire Desjonqueres, Marie Lequoy, Giuliana Amaddeo, Isabelle Fouchard, Gisele N’Kontchou, Clemence M. Canivet, Marianne Ziol, Hélène Regnault, Adrien Lannes, Frederic Oberti, Jerome Boursier, and Nathalie Ganne-Carrie
Subjects: hepatocarcinoma, steatotic liver disease, NAFLD, survival, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Despite its growing incidence, hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) in non-cirrhotic livers remains poorly characterized. We compared the characteristics, management, survival, and trends of MASLD-related HCC in patients with or without underlying cirrhosis in a large multicenter cohort. Methods: A total of 354 cases of MASLD-related HCC presented at the liver tumor meetings of four French university hospitals between 2007 and 2018 were included in the study. Data were extracted from the meetings’ databases and from the French Birth and Death Registry. Results: Of HCC cases, 35% occurred in the absence of cirrhosis. HCC was diagnosed through screening in 60% of patients with cirrhosis, and incidentally in 72% of patients without it. Patients without cirrhosis were older, had a greater tumor burden, but also better liver function than patients with cirrhosis. Patients without cirrhosis showed better overall survival than those with cirrhosis (p = 0.043). However, cirrhosis was not independently associated with overall survival, the independent predictors were age, liver function, tumor burden and BCLC classification. Patients without cirrhosis underwent surgery more frequently than patients with cirrhosis (41% vs. 11%, p
Published: 2024
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4. Treatment with bulevirtide in HIV-infected patients with chronic hepatitis D: ANRS HD EP01 BuleDelta and compassionate cohort

Author: Victor de Lédinghen, Claire Fougerou-Leurent, Estelle Le Pabic, Stanislas Pol, Dulce Alfaiate, Karine Lacombe, Marie-Noëlle Hilleret, Caroline Lascoux-Combe, Anne Minello, Eric Billaud, Isabelle Rosa, Anne Gervais, Vlad Ratziu, Nathalie Ganne, Georges-Philippe Pageaux, Vincent Leroy, Véronique Loustaud-Ratti, Philippe Mathurin, Julie Chas, Caroline Jezequel, Sophie Métivier, Jérôme Dumortier, Jean-Pierre Arpurt, Tarik Asselah, Bruno Roche, Antonia Le Gruyer, Marc-Antoine Valantin, Caroline Scholtès, Emmanuel Gordien, Christelle Tual, Amel Kortebi, Fatoumata Coulibaly, Eric Rosenthal, Miroslava Subic-Levrero, Dominique Roulot, Fabien Zoulim, François Raffi, Laurent Alric, Patrick Miailhes, Albert Tran, Christiane Stern, Xavier Causse, Simona Tripon, Ghassan Riachi, Olivier Chazouillères, Armando Abergel, Louis d’Alteroche, Jérôme Gournay, Garance Lagadic, Patrizia Carrieri, Ségolène Brichler, Martin Siguier, Jessica Krause, Juliette Foucher, Souad Ben Ali, Magdalena Meszaros, Anne Varaut, and Valérie Canva
Subjects: Cirrhosis, HDV, HBV, Pegylated interferon, Hepatitis D, HDV RNA, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: In France, bulevirtide (BLV) became available in September 2019 through an early access program to treat patients with HDV. The aim of this analysis was to evaluate the efficacy and safety of BLV in patients with HIV and HDV coinfection. Methods: Patients received BLV 2 mg ± pegylated interferon-α (pegIFNα) according to the physician’s decision. The primary endpoint (per-protocol analysis) was the virological response rate at Week 48, defined as the proportion of patients with undetectable serum HDV RNA or a HDV RNA decline >2 log10 IU/ml from baseline. Results: The characteristics of the 38 patients were as follows: 28 male, mean age 47.7 years, and mean baseline HDV RNA viral load 5.7 ± 1.2 log10 IU/ml. Median HIV viral load and mean CD4 count were 32 (30–65) copies/ml and 566 ± 307/mm3, respectively. Eight patients stopped treatment before Week 48. At Week 48, 10 of 19 patients (52.6%) in the 2 mg BLV group and five of seven patients (71.4%) in the 2 mg BLV + pegIFNɑ group had reached virological response (no HDV RNA available in four patients). At Week 48, seven of 19 patients in the 2 mg BLV group and three of six patients in the 2 mg BLV + pegIFNɑ group had a combined response (virological response and normal alanine aminotransferase level). Conclusions: Adults living with HIV coinfected with HDV can be treated by BLV with a virological response in more than 50% of patients. The combination of BLV and pegIFNɑ showed a strong virological response. Impact and implications: Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported.
Published: 2024
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5. International survey among hepatologists and pulmonologists on the hepatic hydrothorax: plea for recommendations

Author: Jean-François David Cadranel, Isabelle Ollivier-Hourmand, Jacques Cadranel, Thierry Thevenot, Honoré Zougmore, Eric Nguyen-Khac, Christophe Bureau, Manon Allaire, Jean-Baptiste Nousbaum, Véronique Loustaud-Ratti, Xavier Causse, Philippe Sogni, Bertrand Hanslik, Marc Bourliere, Jean-Marie Peron, Nathalie Ganne-Carrie, Thong Dao, Dominique Thabut, Bernard. Maitre, Nabil Debzi, Ryad Smadhi, Roger Sombie, Raimi Kpossou, Olivier Nouel, Julien Bissonnette, Isaac Ruiz, Mourad Medmoun, Sergio Negrin Dastis, Pierre Deltenre, Florent Artru, Chantal Raherison, Laure Elkrief, and Tristan Lemagoarou
Subjects: Hepatic hydrothorax, Therapeutic pleural puncture, Albumin infusion, Spontaneous bacterial empyema, Talcage pleurodesis, Indwelling pleural catheter, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Abstract Background The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. Methods Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. Results Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p
Published: 2023
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6. Implementing advanced practice nursing in France: A country‐wide survey 2 years after its introduction

Author: Julie Devictor, Espérie Burnet, Tatiana Henriot, Anne Leclercq, Nathalie Ganne‐Carrie, Kelley Kilpatrick, and Ljiljana Jovic
Subjects: advanced practice nursing, barriers and facilitators, French healthcare system, implementation, primary care, Nursing, RT1-120
Abstract: Abstract Objectives To examine the characteristics of the first Advanced Practice Nurses in France and to compare the French model to international standards. Background Common barriers and facilitators to their integration in healthcare provision have been identified internationally. In France, the legislative framework was introduced in 2016, and the first graduates entered the workforce in 2019. Methods The French model was examined in comparison with Hamric's conceptual framework and to the International Council of Nurses' guidelines and definitions. A cross‐sectional survey was also conducted, using three self‐administered online questionnaires. Two were distributed to 2019 and 2020 graduates and a third to the accredited programme directors. The characteristics of advanced practice nursing graduates were described and compared based on employment status and field of practice (primary vs secondary/tertiary care). Results Although the French model of advanced practice nursing meets Hamric's primary criteria and core competencies, it does not differentiate between Nurse Practitioner and Clinical Nurse Specialist roles. Of the 320 students enrolled in one of the 11 accredited training programmes 165 participated in the survey. Mean age was 40, and mean prior nursing experience was 15 years. By February 2021, 30% of respondents were still employed as Registered Nurses. Barriers to practice included insufficient income generation (primary care), the lack of position creation (secondary/tertiary care), the physician‐dependent patient referral process and delays in prescription credentials approval. Conclusions The implementation of advanced practice nursing in France faces several barriers. Legislative adjustments and greater financial incentives to practice seem warranted. Relevance to clinical practice: as in other countries, France introduced advanced practice nursing to respond to the Public Health challenge of improving access to quality health care in the context of increasing chronic disease prevalence and limited resource allocation. Facilitating its integration in the healthcare provision landscape seems paramount.
Published: 2023
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7. Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area: What's new 12 months later?

Author: Raffaele Brustia, Mohamed Bouattour, Manon Allaire, Marie Lequoy, Clémence Hollande, Hélène Regnault, Lorraine Blaise, Nathalie Ganne-Carrié, Valérie Vilgrain, Edouard Larrey, Chetana Lim, Olivier Scatton, Sanaa El Mouhadi, Violaine Ozenne, François Paye, Pierre Balladur, Anthony Dohan, Pierre-Philippe Massault, Stanislas Pol, Marco Dioguardi Burgio, Ailton Sepulveda, Francois Cauchy, Alain Luciani, Daniele Sommacale, Vincent Leroy, Julien Calderaro, Francoise Roudot-Thoraval, Jean-Charles Nault, and Giuliana Amaddeo
Subjects: 2019-nCoV, COVID-19, Management, Hepatocellular carcinoma, cirrhosis, Specialties of internal medicine, RC581-951
Abstract: Introduction and Objectives: The lockdown policy introduced in 2020 to minimize the spread of the COVID-19 pandemic, significantly affected the management and care of patients affected by hepatocellular carcinoma (HCC). The aim of this follow-up study was to determine the 12 months impact of the COVID-19 pandemic on the cohort of patients affected by HCC during the lockdown, within six French academic referral centers in the metropolitan area of Paris. Materials and Methods: We performed a 12 months follow-up of the cross-sectional study cohort included in 2020 on the management of patients affected by HCC during the first six weeks of the COVID-19 pandemic (exposed), compared to the same period in 2019 (unexposed). Overall survival were compared between the groups. Predictors of mortality were analysed with Cox regression. Results: From the initial cohort, 575 patients were included (n = 263 Exposed_COVID, n = 312 Unexposed_COVID). Overall and disease free survival at 12 months were 59.9 ± 3.2% vs. 74.3 ± 2.5% (p
Published: 2023
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8. 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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9. Fragility index of positive phase II and III randomised clinical trials of treatments for hepatocellular carcinoma (2002–2022)

Author: Sabrina Sidali, Nanthara Sritharan, Claudia Campani, Jules Gregory, François Durand, Nathalie Ganne-Carrié, Maxime Ronot, Vincent Lévy, and Jean-Charles Nault
Subjects: Fragility index, Fragility quotient, p value, Hepatocellular carcinoma, Randomised controlled clinical trial, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: The fragility index (FI), i.e., theminimum number of best survivors reassigned to the control group required to revert the statistically significant result of a clinical trial to non-significant, is a metric to evaluate the robustness of randomized controlled trials (RCTs). We aimed to assess the FI in the field of HCC. Methods: This is a retrospective analysis of phase 2 and 3 RCTs for the treatment of HCC published between 2002 and 2022. We included two-arm studies with 1:1 randomization and significant positive results for a primary time-to-event endpoint for the FI calculation, which involves the iterative addition of a best survivor from the experimental group to the control group, until positive significance (p
Published: 2023
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10. Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis

Author: Georges-Philippe Pageaux, Clovis Lusivika Nzinga, Nathalie Ganne, Didier Samuel, Céline Dorival, Fabien Zoulim, Carole Cagnot, Thomas Decaens, Dominique Thabut, Tarik Asselah, Philippe Mathurin, François Habersetzer, Jean-Pierre Bronowicki, Dominique Guyader, Isabelle Rosa, Vincent Leroy, Olivier Chazouilleres, Victor de Ledinghen, Marc Bourliere, Xavier Causse, Paul Cales, Sophie Metivier, Véronique Loustaud-Ratti, Ghassan Riachi, Laurent Alric, Moana Gelu-Simeon, Anne Minello, Jérôme Gournay, Claire Geist, Albert Tran, Armand Abergel, Isabelle Portal, Louis d’Alteroche, François Raffi, Hélène Fontaine, Fabrice Carrat, Stanislas Pol, and For the French ANRS CO22 Hepather Cohort
Subjects: Hepatitis C virus, Decompensated cirrhosis, Direst-acting antiviral agents, Survival, Hepatocellular carcinoma, Sustained virological response, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background In HCV-infected patients with advanced liver disease, the direct antiviral agents-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with direct antiviral agents from the French ANRS CO22 HEPATHER cohort. Methods We identified HCV patients who had experienced an episode of decompensated cirrhosis. Study outcomes were all-cause mortality, liver-related or non-liver-related deaths, hepatocellular carcinoma, liver transplantation. Secondary study outcomes were sustained virological response and its clinical benefits. Results 559 patients met the identification criteria, of which 483 received direct antiviral agents and 76 remained untreated after inclusion in the cohort. The median follow-up time was 39.7 (IQR: 22.7–51) months. After adjustment for multivariate analysis, exposure to direct antiviral agents was associated with a decrease in all-cause mortality (HR 0.45, 95% CI 0.24–0.84, p = 0.01) and non-liver-related death (HR 0.26, 95% CI 0.08–0.82, p = 0.02), and was not associated with liver-related death, decrease in hepatocellular carcinoma and need for liver transplantation. The sustained virological response was 88%. According to adjusted multivariable analysis, sustained virological response achievement was associated with a decrease in all-cause mortality (HR 0.29, 95% CI 0.15–0.54, p
Published: 2022
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11. Systemic treatments with tyrosine kinase inhibitor and platinum-based chemotherapy in patients with unresectable or metastatic hepatocholangiocarcinoma

Author: Elia Gigante, Christian Hobeika, Brigitte Le Bail, Valérie Paradis, David Tougeron, Marie Lequoy, Mohamed Bouattour, Jean-Frederic Blanc, Nathalie Ganne-Carrié, Henri Tran, Clémence Hollande, Manon Allaire, Giuliana Amaddeo, Hélène Regnault, Paul Vigneron, Maxime Ronot, Laure Elkrief, Gontran Verset, Eric Trepo, Aziz Zaanan, Marianne Ziol, Massih Ningarhari, Julien Calderaro, Julien Edeline, and Jean-Charles Nault
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Backgrounds and aims: Even if no systemic treatment is currently validated for unresectable hepato-cholangiocarcinoma (cHCC-CCA), tyrosine kinase inhibitors (TKI), and platinum-based chemotherapy are frequently used in clinical practice. Our study aims to describe the effectiveness of first-line systemic treatments in patients with cHCC-CCA. Patients and Methods: Patients with histological diagnosis of unresectable or metastatic cHCC-CCA confirmed by a centralized review (WHO classification 2019) and who received systemic treatment from 2009 to 2020 were included retrospectively in 11 centers. The outcomes of patients with cHCC-CCA were compared with patients with hepatocellular carcinoma (HCC) treated by sorafenib (n=117) and with intrahepatic cholangiocarcinoma (iCCA, n=94) treated mainly by platinum-based chemotherapy using a frailty Cox model. The efficacy of tyrosine kinase inhibitors and platinum-based chemotherapies in patients with cHCC-CCA was assessed using a doubly robust estimator. Results: A total of 83 patients with cHCC-CCA were included and were predominantly male (72%) with underlying cirrhosis (55%). 67% of patients had extrahepatic metastases and 31% macrovascular tumor invasion. cHCC-CCAs were more often developed on cirrhosis (55.4%) than iCCA (26.6%) but less frequently than HCC (80.2%)(p
Published: 2022
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12. Management of patients with pre-therapeutic advanced liver fibrosis following HCV eradicationKey points

Author: Pierre Nahon and Nathalie Ganne-Carrié
Subjects: Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Summary: Patients with HCV-related bridging fibrosis or cirrhosis remain at risk of developing life-threatening complications even after achieving a sustained virological response. Although it is reduced, the risk of liver-related events in these patients justifies their inclusion in surveillance programmes dedicated to the early detection of hepatocellular carcinoma and the screening for portal hypertension. Biochemical parameters or non-invasive tests might indicate the potential progression of liver injury despite viral clearance. Specific attention must be focused on the management of comorbidities, while dedicated educational programmes must be encouraged to increase compliance and commitment to surveillance. Better knowledge of the long-term evolution of these patients, who now live longer, is essential to improve risk stratification and refine screening strategies in this growing population. Keywords: HCV, Hepatocellular carcinoma, Liver failure, Portal hypertension, surveillance, SVR
Published: 2019
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13. Safety and efficacy of the combination simeprevir-sofosbuvir in HCV genotype 1- and 4-mono-infected patients from the French ANRS CO22 hepather cohort

Author: Anne Laurain, Sophie Metivier, Georges Haour, Dominique Larrey, Céline Dorival, Christophe Hezode, Fabien Zoulim, Patrick Marcellin, Marc Bourliere, Jean-Pierre Zarski, Dominique Thabut, Laurent Alric, Nathalie Ganne-Carrie, Paul Cales, Jean-Pierre Bronowicki, Ghassan Riachi, Claire Geist, Xavier Causse, Armand Abergel, Olivier Chazouilleres, Philippe Mathurin, Dominique Guyader, Didier Samuel, Albert Tran, Véronique Loustaud-Ratti, Ventzislava Petrov-Sanchez, Alpha Diallo, Clovis Luzivika-Nzinga, Hélène Fontaine, Fabrice Carrat, Stanislas Pol, and on behalf of the ANRS/AFEF HEPATHER study group
Subjects: Direct acting antivirals, Hepatitis C virus, Real life cohort, Simeprevir, Sofosbuvir, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Although real-life results of sofosbuvir/simeprevir have been extensively reported from the United States, data from other geographical areas are limited. In the French observational cohort, ANRS CO22 HEPATHER, 9432 patients were given the new oral antivirals from December 2013 to June 30, 2018. We report the results of sofosbuvir/simeprevir in genotypes 1- and 4-infected patients. Methods Demographics and history of liver disease were collected at entry in the cohort. Clinical, adverse events, and virological data were collected throughout treatment and post-treatment follow-up. The choice of treatment duration or addition of ribavirin was left up to the physician. Results Five hundred ninety-nine HCV (467 genotype 1 and 132 genotype 4) mono-infected, naïve for all oral-DAAs regimen patients were given sofosbuvir/simeprevir with (n = 63) or without ribavirin (n = 536) for 12 or 24 weeks; 56% had cirrhosis (4% decompensated) and 71% had prior treatment failure to interferon-based regimen. 7 patients (1.16%) were lost to follow-up. The overall SVR12 rate was 92.6%. The SVR12 was 90% in GT1a, 94.2% in GT1b and 91.6% in GT4 with no significant difference for genotype, treatment duration or ribavirin addition. Severity of liver disease was not associated with a lower SVR12 rate on multivariate analysis but was associated with a higher rate of severe side effects. Early treatment discontinuations were rare; no new safety signals were reported. Conclusion In this real life, observational, prospective cohort study, the 12-week sofosbuvir/simeprevir+/−ribavirin combination appears to be efficient and safe. Trial registration Trial registration with ClinicalTrials.gov NCT01953458.
Published: 2019
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14. Impact of cirrhosis aetiology on incidence and prognosis of hepatocellular carcinoma diagnosed during surveillance

Author: Nathalie Ganne-Carrié, Pierre Nahon, Cendrine Chaffaut, Gisèle N’Kontchou, Richard Layese, Etienne Audureau, Sylvie Chevret, Isabelle Archambeaud, Louis d’Alteroche, Frédéric Oberti, Dominique Roulot, Christophe Moreno, Alexandre Louvet, Thông Dao, Romain Moirand, Odile Goria, Eric Nguyen-Khac, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Stanislas Pol, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Jean-Marie Péron, Albert Tran, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, Tarik Asselah, Dominique Guyader, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Jean-Pierre Bronowicki, Thomas Decaens, Ghassan Riachi, Paul Calès, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Claire Wartelle, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Brigitte Bernard-Chabert, Sophie Hillaire, and Vincent Di Martino
Subjects: alcoholic liver disease, cirrhosis, primary liver cancer, competing risk analysis, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: In this study we aimed to analyse the impact of the aetiology of cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program. Methods: Individual data from a randomized trial and 2 prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models. Results: Among 3,533 patients (1,926 virus [VIR], 1,167 alcohol [ALC], 440 combined [MIX]), 431 were diagnosed with HCC after a median follow-up of 57.1 months. The 5-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but early BCLC stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of worse ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact. Conclusion: Compared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have: i) the lowest 5-year HCC incidence; ii) worse overall prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment. Lay summary: It has been suggested that early detection of hepatocellular carcinoma (HCC) may be futile in patients with alcohol-related cirrhosis. By comparing outcomes in more than 3,000 patients with compensated cirrhosis included in surveillance programs, this study suggests that HCC surveillance enables early diagnosis in most patients with alcohol-related cirrhosis despite a higher competing risk of death in these patients. We also report similar access to first-line curative HCC treatment in these patients compared to those with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death irrespective of the cause of cirrhosis. Registration: CHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links (https://clinicaltrials.gov/ct2/show/NCT00190385) and https://clinicaltrials.gov/ct2/show/NCT01213927, respectively). The full CirVir protocol is available via the ANRS Web site (http://anrs.fr).
Published: 2021
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15. New insights into the pathophysiology and clinical care of rare primary liver cancersKey points

Author: Elia Gigante, Valérie Paradis, Maxime Ronot, François Cauchy, Olivier Soubrane, Nathalie Ganne-Carrié, and Jean-Charles Nault
Subjects: Mixed tumor, Hepatocholangiocarcinoma, Fibrolamellar carcinoma, Hepatic hemangioendothelioma, Hepatocellular carcinoma, Hepatic angiosarcoma, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Summary: Hepatocholangiocarcinoma, fibrolamellar carcinoma, hepatic haemangioendothelioma and hepatic angiosarcoma represent less than 5% of primary liver cancers. Fibrolamellar carcinoma and hepatic haemangioendothelioma are driven by unique somatic genetic alterations (DNAJB1-PRKCA and CAMTA1-WWTR1 fusions, respectively), while the pathogenesis of hepatocholangiocarcinoma remains more complex, as suggested by its histological diversity. Histology is the gold standard for diagnosis, which remains challenging even in an expert centre because of the low incidences of these liver cancers. Resection, when feasible, is the cornerstone of treatment, together with liver transplantation for hepatic haemangioendothelioma. The role of locoregional therapies and systemic treatments remains poorly studied. In this review, we aim to describe the recent advances in terms of diagnosis and clinical management of these rare primary liver cancers.
Published: 2021
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16. Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area

Author: Giuliana Amaddeo, Raffaele Brustia, Manon Allaire, Marie Lequoy, Clémence Hollande, Hélène Regnault, Lorraine Blaise, Nathalie Ganne-Carrié, Olivier Séror, Edouard Larrey, Chetana Lim, Olivier Scatton, Sanaa El Mouhadi, Violaine Ozenne, François Paye, Pierre Balladur, Anthony Dohan, Pierre-Philippe Massault, Stanislas Pol, Marco Dioguardi Burgio, Valérie Vilgrain, Ailton Sepulveda, Francois Cauchy, Alain Luciani, Daniele Sommacale, Vincent Leroy, Francoise Roudot-Thoraval, Mohamed Bouattour, and Jean-Charles Nault
Subjects: 2019-nCoV, COVID-19, Management, Hepatocellular carcinoma, Cirrhosis, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Patients affected by hepatocellular carcinoma (HCC) represent a vulnerable population during the COVID-19 pandemic and may suffer from altered allocation of healthcare resources. The aim of this study was to determine the impact of the COVID-19 pandemic on the management of patients with HCC within 6 referral centres in the metropolitan area of Paris, France. Methods: We performed a multicentre, retrospective, cross-sectional study on the management of patients with HCC during the first 6 weeks of the COVID-19 pandemic (exposed group), compared with the same period in 2019 (unexposed group). We included all patients discussed in multidisciplinary tumour board (MTB) meetings and/or patients undergoing a radiological or surgical programmed procedure during the study period, with curative or palliative intent. Endpoints were the number of patients with a modification in the treatment strategy, or a delay in decision-to-treat. Results: After screening, n = 670 patients were included (n = 293 exposed to COVID, n = 377 unexposed to COVID). Fewer patients with HCC presented to the MTB in 2020 (p = 0.034) and fewer had a first diagnosis of HCC (n = 104 exposed to COVID, n = 143 unexposed to COVID, p = 0.083). Treatment strategy was modified in 13.1% of patients, with no differences between the 2 periods. Nevertheless, 21.5% vs. 9.5% of patients experienced a treatment delay longer than 1 month in 2020 compared with 2019 (p
Published: 2021
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17. 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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18. Influence of ABO Blood Group on the Risk of Complications in Alcoholic or Viral C Cirrhosis? (ABOCIRRALVIR)

Author: Thong DAO, Annie BOREL-DERLON, Nathalie GANNE-CARRIE, Pierre NAHON, and Sylvie CHEVRET
Published: 2020

19. Cost-Utility Analysis of Transarterial Radioembolization With Yttrium-90 Resin Microspheres Compared With Sorafenib in Locally Advanced and Inoperable Hepatocellular Carcinoma

Author: Assenat, Eric, Delhom-Christol, Elisabeth, Guiu, Boris, Ilonca, Alina D., Lonjon, Julie, Pageaux, Georges-Philippe, Abdel-Rehim, Mohamed, Al-laham, Wassim, Bouattour, Mohamed, Castera, Laurent, Dieudonné, Arnaud, Lebtahi, Rachida, Ronot, Maxime, Sibert, Annie, Vilgrain, Valérie, Barraud, Hélène, Bazin, Christophe, Bronowicki, Jean-Pierre, Laurent, Valérie, Mathias, Elodie, Chagneau-Derrode, Carine, Perdrisot, Rémy, Silvain, Christine, Tasu, Jean-Pierre, RenéGerolami, Patrick Borentain, Mundler, Olivier, Seitz, Jean-Francois, Vidal, Vincent, Aubé, Christophe, Bouvier, Antoine, Couturier, Olivier, Oberti, Frédéric, Vervueren, Laurent, Brenot-Rossi, Isabelle, Raoul, Jean-Luc, Sar-ran, Anthony, Chalaye, Julia, Costentin, Charlotte, Itti, Emmanuel, Kobeiter, Hicham, Luciani, Alain, Adam, René, Lewin, Maïté, Samuel, Didier, Edeline, Julien, Garin, Etienne, Rolland, Yan, Archambeaud, Isabelle, Eugene, Thomas, Frampas, Eric, Cassinotto, Christophe, Guyot, Martine, Hiriart, Jean-Baptiste, Lapuyade, Bruno, Vergniol, Julien, Bachellier, Philippe, Detour, Julien, Duclos, Bernard, Greget, Michel, Habersetzer, Francois, Imperiale, Alessio, Merle, Philippe, Rode, Agnès, Morvan, Julie, Nguyen-Khac, Eric, Yzet, Thierry, Baudin, Guillaume, Chevallier, Patrick, Mahamat, Abakar, Piche, Thierry, Razzouk, Micheline, Hillon, Patrick, Loffroy, Romaric, Toubeau, Michel, Vincent, Julie, Barabino, Gabriele, Bouarioua, Nadia, Cuilleron, Muriel, Ecochard, Marie, Prevot-Bitot, Nathalie, Leroy, Vincent, Roux, Julie, Sengel, Christian, Bourcier, Valérie, Carrie, Nathalie Ganne, Seror, Olivier, Costo, Sylvie, Dao, Thông, Pelage, Jean-Pierre, Dumortier, Jérôme, Giammarile, Francesco, Valette, Pierre-Jean, Ghazzar, Nadia, Pellerin, Olivier, Taieb, Julien, Weinmann, Pierre, Berlot, Alexandra Heurgue, Marcus, Claude, Sommacale, Daniele, Castilla-Lièvre, Maria-Angéla, Maitre, Sophie, Marthey, Lysiane, Zarca, Kevin, Mimouni, Maroua, Pereira, Helena, Chatellier, Gilles, and Durand-Zaleski, Isabelle
Published: 2021
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20. Circulating tumour DNA in patients with hepatocellular carcinoma across tumour stages and treatments.

Author: Campani, Claudia, Imbeaud, Sandrine, Couchy, Gabrielle, Ziol, Marianne, Hirsch, Theo Z., Rebouissou, Sandra, Noblet, Bénédicte, Nahon, Pierre, Hormigos, Katia, Sidali, Sabrina, Seror, Olivier, Taly, Valerie, Carrie, Nathalie Ganne, Laurent-Puig, Pierre, Zucman-Rossi, Jessica, and Nault, Jean-Charles
Subjects: CELL-free DNA, CIRCULATING tumor DNA, SOMATIC mutation, TELOMERASE reverse transcriptase, DNA analysis, HORMONE receptor positive breast cancer
Published: 2024
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21. Integrating genetic variants into clinical models for hepatocellular carcinoma risk stratification in cirrhosis

Author: Pierre Nahon, Jessica Bamba-Funck, Richard Layese, Eric Trépo, Jessica Zucman-Rossi, Carole Cagnot, Nathalie Ganne-Carrié, Cendrine Chaffaut, Erwan Guyot, Marianne Ziol, Angela Sutton, Etienne Audureau, Tarik Asselah, Dominique Guyader, Stanislas Pol, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Thomas Decaensi, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, null Louis d’Alteroche, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Isabelle Archambeaud, Louis d’Alteroche, Frédéric Oberti, Christophe Moreno, Alexandre Louvet, Romain Moirand, Odile Goria, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, and Sylvie Chevret
Subjects: Hepatology
Abstract: This study aimed to evaluate the ability of single nucleotide polymorphisms (SNPs) to refine hepatocellular carcinoma (HCC) risk stratification.Six SNPs in PNPLA3, TM6SF2, HSD17B13, APOE, and MBOAT7 affecting lipid turnover and one variant involved in the Wnt-β-catenin pathway (WNT3A-WNT9A rs708113) were assessed in patients with alcohol-related and/or HCV-cured cirrhosis included in HCC surveillance programs (prospective CirVir and CIRRAL cohorts). Their prognostic value for HCC occurrence was assessed using Fine-Gray models combined into a 7-SNP genetic risk score (GRS). Prediction ability of two clinical scores (a routine nongenetic model determined by multivariate analysis and the external aMAP score) without then with the addition of the GRS was evaluated by C-indices. The standardized net benefit was derived from decision curves.Among 1145 patients, 86 (7.5%) developed HCC after 43.7 months. PNPLA3 and WNT3A-WNT9A variants were independently associated with HCC occurrence. The GRS stratified the population into 3 groups with progressively increased 5-yr HCC incidence [Group 1 (n=627, 5.4%), Group 2 (n=276, 10.7%), and Group 3 (n=242, 15.3%); P0.001]. The multivariate model identified age, male sex, diabetes, platelet count, GGT levels, albuminemia and the GRS as independent risk factors. The clinical model performance for 5-yr HCC prediction was similar to that of the aMAP score (C-Index 0.769). The addition of the GRS to both scores modestly improved their performance (C-Index 0.786 and 0.783, respectively). This finding was confirmed by decision curve analyses showing only fair clinical net benefit.Patients with cirrhosis can be stratified into HCC risk classes by variants affecting lipid turnover and Wnt-β-catenin pathway. The incorporation of this genetic information modestly improves the performance of clinical scores.The identification of patients at higher probability of developing liver cancer is pivotal to improve the performance of surveillance. Risk assessment can be achieved by combining several clinical and biological parameters used in routine practice. The addition of patients' genetic characteristics can modestly improve this prediction and will ultimately pave the way for precision medicine in patients eligible for HCC surveillance, allowing physicians to trigger personalized screening strategies.
Published: 2023
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22. A history of variceal bleeding is associated with further bleeding under atezolizumab–bevacizumab in patients with <scp>HCC</scp>

Author: Edouard Larrey, Bertille Campion, Manon Evain, Philippe Sultanik, Lorraine Blaise, Héloïse Giudicelli, Mathilde Wagner, Philippe Cluzel, Marika Rudler, Nathalie Ganne‐Carrié, Dominique Thabut, and Manon Allaire
Subjects: Male, Bevacizumab, Liver Cirrhosis, Carcinoma, Hepatocellular, Hepatology, Liver Neoplasms, Humans, Prospective Studies, Sorafenib, Esophageal and Gastric Varices, Gastrointestinal Hemorrhage, Retrospective Studies
Abstract: Atezolizumab-bevacizumab is the new standard for advanced hepatocellular carcinoma (HCC) but its impact on portal hypertension (PHT) is unknown. We aimed to identify predictive factors of acute variceal bleeding (AVB) and to monitor PHT parameters under treatment.We conducted a prospective study including all cirrhotic patients treated with atezolizumab-bevacizumab since 2020. We performed monitoring of PHT using upper endoscopy at inclusion and at 6 months and hepatic venous pressure gradient (HVPG) at inclusion, 3 and 6 months after the beginning of treatment. We also included a retrospective series of patients treated with sorafenib. Time-to-events data were estimated by Kaplan-Meier with the log-rank test, along with Cox models.Forty-three patients treated with atezolizumab-bevacizumab were included (male 79.1%, Child-Pugh A 86%). At baseline, 48.8% were treated with curative anticoagulation, 16.3% already experienced AVB and 25.6% had large oesophageal varices (EV). Sorafenib group characteristics were similar. Vascular invasion was present in 60.5% and median was HVPG 8.5 mm Hg. No significant modification in HVPG and EV size was observed at 6 months in the whole cohort but also when considering vascular invasion and radiological response. 14% presented AVB within a median time of occurrence of 3 months, without bleeding-related death. In multivariate analysis, history of AVB (HR = 10.58, p = .03) was associated with AVB. AVB incidence was higher in atezolizumab-bevacizumab compared to sorafenib group (21% vs. 5% at 1 year, p = .02).Atezolizumab-bevacizumab treatment was associated with a higher risk of AVB compared to sorafenib. A history of AVB was associated with AVB during follow-up, which questions the use of bevacizumab in this setting.
Published: 2022
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23. Impact of sarcopenia on tumor response and survival outcomes in patients with hepatocellular carcinoma treated by trans-arterial (chemo)-embolization

Author: Gael, Roth, Yann, Teyssier, Maxime, Benhamou, Mélodie, Abousalihac, Stefano, Caruso, Christian, Sengel, Olivier, Seror, Julien, Ghelfi, Arnaud, Seigneurin, Nathalie, Ganne-Carrie, Elia, Gigante, Lorraine, Blaise, Olivier, Sutter, Thomas, Decaens, and Jean-Charles, Nault
Subjects: Sarcopenia, Carcinoma, Hepatocellular, Liver Neoplasms, Malnutrition, Gastroenterology, Humans, General Medicine, Chemoembolization, Therapeutic, Retrospective Studies
Abstract: At the diagnosis of hepatocellular carcinoma (HCC), more than 90% of HCC patients present cirrhosis, a clinical condition often associated to malnutrition. Sarcopenia is an indirect marker of malnutrition assessable on computed tomography (CT).To evaluate the prognostic value of sarcopenia in patients with HCC treated by trans-arterial (chemo)-embolization.Patients with HCC treated by a first session of trans-arterial (chemo)embolization and an available CT scan before treatment were included. Sarcopenia was assessed using skeletal muscle index at baseline and at the first radiological assessment. Radiological response was recorded after the first session of treatment using mRECIST.Of 225 patients treated by trans-arterial bland embolization (Sarcopenia is associated with tumor progression and poor survival outcomes after trans-arterial (chemo)-embolization for HCC.
Published: 2022
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24. Perspective on This Article from Effect of Long-term Propranolol Treatment on Hepatocellular Carcinoma Incidence in Patients with HCV-Associated Cirrhosis

Author: Michel Beaugrand, Eric Vicaut, Jean-Claude Trinchet, Nathalie Ganne-Carrie, Véronique Grando-Lemaire, Valérie Bourcier, Dominique Roulot, Amel Mahmoudi, Mounir Aout, and Gisèle Nkontchou
Abstract: Perspective on This Article from Effect of Long-term Propranolol Treatment on Hepatocellular Carcinoma Incidence in Patients with HCV-Associated Cirrhosis
Published: 2023
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25. Data from Effect of Long-term Propranolol Treatment on Hepatocellular Carcinoma Incidence in Patients with HCV-Associated Cirrhosis

Author: Michel Beaugrand, Eric Vicaut, Jean-Claude Trinchet, Nathalie Ganne-Carrie, Véronique Grando-Lemaire, Valérie Bourcier, Dominique Roulot, Amel Mahmoudi, Mounir Aout, and Gisèle Nkontchou
Abstract: Propranolol bears antioxidant, anti-inflammatory, and antiangiogenic properties and antitumoral effects and therefore is potentially active in the prevention of hepatocellular carcinoma (HCC). We retrospectively assessed the impact of propranolol treatment on HCC occurrence in a cohort of 291 patients with compensated viral C (HCV) cirrhosis, prospectively followed and screened for HCC detection.Of the 291 patients included in the cohort, 93 patients [50 males: mean age, 59.5 ± 12 years; body mass index (BMI), 25.7 ± 4.4 kg/m2; and platelet count, 111 ± 53 Giga/L] developed esophageal varices (OV) or had OV at inclusion and 198 patients (111 males: mean age, 55.8 ± 13 years; BMI, 25.7 ± 5 kg/m2; platelet count, 137 ± 59 Giga/L) did not. Among patients with OV, 50 received treatment by propranolol. During a median follow-up of 54 months interquartile range (32–82), 61 patients developed an HCC. The 3- and 5-year HCC incidence was 4% and 4%, and 10% and 20% for patients treated and not treated by propranolol, respectively (Gray test, P = 0.03). In multivariate analysis, propranolol treatment was associated with a decrease risk of HCC occurrence [HR, 0.25; 95% confidence interval (CI), 0.09–0.65; P = 0.004], and was the only independent predictive factor of HCC occurrence in patients with OV (HR, 0.16; CI, 0.06–0.45; P = 0.0005). The benefit of propranolol was further supported by propensity scores analyses.Conclusion: This retrospective long-term observational study suggests that propranolol treatment may decrease HCC occurrence in patients with HCV cirrhosis. These findings need to be verified by prospective clinical trial. Cancer Prev Res; 5(8); 1007–14. ©2012 AACR.
Published: 2023
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26. Effect of lockdown on digestive system cancer care amongst older patients during the first wave of COVID-19: The CADIGCOVAGE multicentre cohort study

Author: Nathalie Ganne, François Hemery, Laurent Quero, Frédéric Prat, Thomas Aparicio, Nicola de Angelis, Gilles Galula, Richard Layese, Marc-Antoine Benderra, Atanas Pachev, Christophe Tournigand, Elena Paillaud, Florence Canouï-Poitrine, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, Cooperator Multidisciplinary Oncology Group (GERCOR), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Département de Santé Publique [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Service d'Oncologie médicale [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Male, Paris, medicine.medical_specialty, Digestive cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Digestive System Neoplasms, Health Services Accessibility, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Lockdown, Older patients, medicine, Humans, 030212 general & internal medicine, Pandemics, Aged, Retrospective Studies, Aged, 80 and over, Public health, Hepatology, SARS-CoV-2, business.industry, Mortality rate, Gastroenterology, COVID-19, Cancer, Emergency department, medicine.disease, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Communicable Disease Control, Cohort, Female, Observational study, business, Cohort study
Abstract: International audience; Background: The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and treatment. Most patients newly diagnosed with digestive system cancer are aged 65 and over. Methods: We performed a retrospective, observational, multicentre cohort study based on prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer between January 2018 until August 2020 were enroled. Results: Data on 7882 patients were analysed. The first COVID-19 lockdown period led to a 42.4% decrease in newly treated digestive system cancers, and the post-lockdown period was associated with a 17% decrease. The decrease in newly treated digestive system cancer did not differ as a function of age, sex, comorbidities, primary tumour site, and disease stage. The proportion of patients admitted to an emergency department increased during the lockdown period. We do not observe a higher 3-month mortality rate in 2020, relative to the corresponding calendar periods in 2018 and 2019. Conclusion: To avoid a decrease in newly treated cancers during future lockdown periods, access to healthcare will have to be modified. Although 3-month mortality did not increase in any of the patient subgroups, the 2020 cohort must be followed up for long-term mortality.
Published: 2022
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27. Supplementary Data from ESM1 as a Marker of Macrotrabecular-Massive Hepatocellular Carcinoma

Author: Marianne Ziol, Olivier Seror, Jessica Zucman-Rossi, Nathalie Ganne-Carrié, Jean-Michel Pawlotsky, Alexis Laurent, Christophe Aubé, Valérie Paradis, Boris Guiu, Nathalie Barget, Jeanne Ramos, Georges Philippe Pageaux, Valérie Vilgrain, Mohamed Bouattour, Sophie Michalak, Frédéric Oberti, Justine Cohen, Jean-Charles Nault, Hélène Regnault, Giuliana Amaddeo, Alain Luciani, Stefano Caruso, Marouane Boubaya, Cong Trung Nguyen, Léa Meunier, and Julien Calderaro
Abstract: Supplemental Data
Published: 2023
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28. Supplementary Table 1 from Serum Proteoglycans as Prognostic Biomarkers of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis

Author: Pierre Nahon, Angela Sutton, Maryse Delehedde, Nathalie Charnaux, Philippe Lasalle, Jessica Coelho, Jean-Claude Trinchet, Olivier Seror, Michel Beaugrand, Gisèle N'Kontchou, Nathalie Ganne-Carrie, Sylvie Chevret, Christelle Laguillier, Erwan Guyot, and Jean-Charles Nault
Abstract: PDF file - 72K, Clinical and biological variables associated with overall mortality and recurrence-free survival in patients with early HCC based on Cox univariable and multivariable models.
Published: 2023
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29. Supplementary Material and Methods, SUpplementary Figures 1-2, Supplementary Tables 1-5, Supplementary References from Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity In Vitro

Author: Jessica Zucman-Rossi, Marianne Ziol, Jean-Charles Nault, Nathalie Ganne-Carrié, Leanne de Koning, Bettina Grasl-Kraupp, Paulette Bioulac-Sage, Gabrielle Couchy, Yoann Martin, Nataliya Rohr-Udilova, Anna-Line Calatayud, Sandrine Imbeaud, Samia Rekik, Tiziana La Bella, and Sandra Rebouissou
Abstract: Supplementary Figure 1. Sensitivity to selective MET inhibitors in liver cancer cell lines is related to MET gene amplification. Supplementary Figure 2. Tivantinib sensitivity is associated with high expression of genes involved in cell cycle regulation. Supplementary Table 1. Liver cancer cell lines. Supplementary Table 2. Clinical features of HCC series. Supplementary Table 3. List of the 188 genes analyzed by quantitative RT-PCR. Supplementary Table 4. Mutations and copy number variations identified in 13 genes among the 35 liver cancer cell lines (GRCh37). Supplementary Table 5. Association between tivantinib sensitivity and mutation status of the 12 most frequently mutated genes in HCC tumors and MET across the panel of 35 liver cancer cell lines.
Published: 2023
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30. Supplementary Figure 1 from Serum Proteoglycans as Prognostic Biomarkers of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis

Author: Pierre Nahon, Angela Sutton, Maryse Delehedde, Nathalie Charnaux, Philippe Lasalle, Jessica Coelho, Jean-Claude Trinchet, Olivier Seror, Michel Beaugrand, Gisèle N'Kontchou, Nathalie Ganne-Carrie, Sylvie Chevret, Christelle Laguillier, Erwan Guyot, and Jean-Charles Nault
Abstract: PDF file - 194K, Subgroup analysis according to the Levels of serum proteoglycans and VEGF.
Published: 2023
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31. Data from Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity In Vitro

Author: Jessica Zucman-Rossi, Marianne Ziol, Jean-Charles Nault, Nathalie Ganne-Carrié, Leanne de Koning, Bettina Grasl-Kraupp, Paulette Bioulac-Sage, Gabrielle Couchy, Yoann Martin, Nataliya Rohr-Udilova, Anna-Line Calatayud, Sandrine Imbeaud, Samia Rekik, Tiziana La Bella, and Sandra Rebouissou
Abstract: Purpose: Tivantinib was initially reported as a selective MET inhibitor and is under phase III evaluation in "MET-high" hepatocellular carcinoma (HCC) patients. However, it has been also proposed as an antimitotic agent. We aimed to evaluate the antitumor effect of tivantinib in HCC cells by combining pharmacologic and molecular profiling.Experimental Design: Sensitivity to tivantinib, JNJ-38877605, PHA-665752, vinblastine, and paclitaxel was tested in a panel of 35 liver cancer cell lines analyzed with exome sequencing, mRNA expression of 188 genes, and protein expression. Drug effect was investigated by Western blot analysis and mitotic index quantification. Expression of candidate biomarkers predicting drug response was analyzed in 310 HCCs.Results: Tivantinib sensitivity profiles in the 35 cell lines were similar to those obtained with antimitotic drugs. It induced blockage of cell mitosis, and high cell proliferation was associated with sensitivity to tivantinib, vinblastine, and paclitaxel. In contrast, tivantinib did not suppress MET signaling, and selective MET inhibitors demonstrated an antiproliferative effect only in MHCC97H, the unique cell line displaying MET gene amplification. HCC tumors with high expression of cell proliferation genes defined a group of patients with poor survival. Interestingly, highly proliferative tumors also demonstrated high MET expression, likely explaining better therapeutic response of MET-high HCC patients to tivantinib.Conclusions: Tivantinib acts as an antimitotic compound, and cell proliferation markers are the best predictors of its antitumor efficacy in cell lines. Ki67 expression should be tested in clinical trials to predict tivantinib response. Clin Cancer Res; 23(15); 4364–75. ©2017 AACR.
Published: 2023
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32. Data from ESM1 as a Marker of Macrotrabecular-Massive Hepatocellular Carcinoma

Author: Marianne Ziol, Olivier Seror, Jessica Zucman-Rossi, Nathalie Ganne-Carrié, Jean-Michel Pawlotsky, Alexis Laurent, Christophe Aubé, Valérie Paradis, Boris Guiu, Nathalie Barget, Jeanne Ramos, Georges Philippe Pageaux, Valérie Vilgrain, Mohamed Bouattour, Sophie Michalak, Frédéric Oberti, Justine Cohen, Jean-Charles Nault, Hélène Regnault, Giuliana Amaddeo, Alain Luciani, Stefano Caruso, Marouane Boubaya, Cong Trung Nguyen, Léa Meunier, and Julien Calderaro
Abstract: Purpose:Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a novel morphological subtype of HCC associated with early relapse after resection or percutaneous ablation, independently of classical clinical and radiological prognostic factors. The aim of the present study was to identify immunohistochemical markers of MTM-HCC, to ease its diagnosis and implementation into clinical practice.Experimental Design:To identify potential biomarkers of MTM-HCC, we first analyzed gene expression profiling data from The Cancer Genome Atlas study and further selected two candidate biomarkers. Performance of both biomarkers for diagnosis of MTM-HCC was further tested by immunohistochemistry in two independent series of 67 and 132 HCC biopsy samples.Results:Analysis of RNA sequencing data showed that MTM-HCC was characterized by a high expression of neoangiogenesis-related genes. Two candidate biomarkers, Endothelial-Specific Molecule 1 (ESM1) and Carbonic Anhydrase IX (CAIX), were selected. In the discovery series, sensitivity and specificity of ESM1 expression by stromal endothelial cells for the detection of MTM-HCC were 97% (28/29), and 92% (35/38), respectively. Sensitivity and specificity of CAIX were 48% (14/29) and 89% (34/38). In the validation set, sensitivity and specificity of ESM1 for the identification of MTM-HCC were 93% (14/15) and 91% (107/117), respectively. Interobserver agreement for ESM1 assessment was good in both series (Cohen Kappa 0.77 and 0.76).Conclusions:Using a molecular-driven selection of biomarkers, we identified ESM1 as a reliable microenvironment immunohistochemical marker of MTM-HCC. The results represent a step toward the implementation of HCC morpho-molecular subtyping into clinical practice.
Published: 2023
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33. Influence of the ABO Blood Group System on Hepatocellular Carcinoma Recurrence After Liver Transplantation

Author: Kayvan, Mohkam, Raëf, Abdallah, Gisèle, N'kontchou, Nathalie, Ganne, Louise, Barbier, Ephrem, Salamé, Petru, Bucur, Michel, Rayar, Fabien, Robin, Karim, Boudjema, Daniel, Pietrasz, Daniel, Cherqui, René, Adam, Chetana, Lim, Eric, Savier, Olivier, Scatton, Charlotte, Maulat, Bertrand, Suc, Fabrice, Muscari, Alexis, Laurent, Christophe, Duvoux, Bruno, Heyd, Célia, Turco, Alexandre, Doussot, Philippe, Merle, Teresa, Antonini, Mickaël, Lesurtel, Cyril, Cossé, François, Durand, Olivier, Soubrane, François, Cauchy, and Jean-Yves, Mabrut
Subjects: Transplantation, Carcinoma, Hepatocellular, Risk Factors, Liver Neoplasms, Humans, Neoplasm Recurrence, Local, ABO Blood-Group System, Liver Transplantation, Retrospective Studies
Abstract: The ABO blood group system may influence tumorigenesis, but its prognostic value in liver transplantation (LT) for hepatocellular carcinoma (HCC) has never been assessed.All consecutive patients who underwent LT for HCC between 2013 and 2017 at 9 centers were analyzed. Predictors of tumor recurrence were identified using multivariable analysis, while comparison between group A and non-A recipients was performed after propensity score matching.Among 925 LT recipients, 406 were blood group A, 94 group B, 380 group O, and 45 group AB. On multivariable analysis, group A was associated with tumor recurrence (hazard ratio [HR] = 1.574 [95% confidence interval; 95% CI = 1.034-2.394] P = 0.034). After propensity score matching, 1- and 5-y recurrence rates were 7.4% and 20.1% in group A recipients versus 3.3% and 13.2% in non-A recipients (HR = 1.66 [95% CI = 1.12-2.45], P = 0.011). One and 5-y recurrence-free survivals were 85.2% and 66.8% in group A recipients versus 88.5% and 71.3% in non-A recipients (HR = 1.38 [95% CI = 1.01-1.90], P = 0.045). Among recipients within Milan criteria (n = 604), 1- and 5-y recurrence rates were 5.8% and 12.7% in group A recipients versus 3.1% and 12.2% in non-A recipients (HR = 1.197 [95% CI = 0.721-1.987], P = 0.485). Among recipients outside Milan criteria (n = 182), 1- and 5-y recurrence rates were 12.1% and 43.8% in group A recipients versus 3.9% and 15.6% in non-A recipients (HR = 3.175 [95% CI = 1.526-6.608], P = 0.002).ABO blood system influences the oncological outcome of recipients undergoing LT for HCC. Its incorporation in the prognostication model of LT for HCC may allow improving the management of LT candidates.
Published: 2021
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34. Sulfatase 2 Along with Syndecan 1 and Glypican 3 Serum Levels are Associated with a Prognostic Value in Patients with Alcoholic Cirrhosis-Related Advanced Hepatocellular Carcinoma

Author: Nesrine Mouhoubi, Jessica Bamba-Funck, Angela Sutton, Lorraine Blaise, Olivier Seror, Nathalie Ganne-Carrié, Marianne Ziol, Gisèle N'Kontchou, Nathalie Charnaux, Pierre Nahon, Jean-Charles Nault, and Erwan Guyot
Subjects: Journal of Hepatocellular Carcinoma
Abstract: Nesrine Mouhoubi,1 Jessica Bamba-Funck,1,2 Angela Sutton,1,2 Lorraine Blaise,3 Olivier Seror,4 Nathalie Ganne-CarriÃ©,3,5 Marianne Ziol,6,7 GisÃ¨le NâKontchou,3 Nathalie Charnaux,1,2 Pierre Nahon,3,5 Jean-Charles Nault,3,5,&ast; Erwan Guyot1,2,&ast; 1UniversitÃ© Sorbonne Paris Nord, Laboratory for VascularTranslational Science, LVTS, INSERM, UMR 1148, Bobigny, F- 93000, France; 2Service de biochimie, HÃ´pital Avicenne, hÃ´pitaux universitaires Paris-Seine-Saint-Denis, Assistance publique HÃ´pitaux de Paris, Bobigny, F-93000, France; 3Service dâhÃ©patologie, HÃ´pital Avicenne, AP-HP, hÃ´pitaux universitaires Paris-Seine-Saint-Denis, Assistance publique HÃ´pitaux de Paris, Bondy, F-93143, France; 4Service de radiologie, HÃ´pital Avicenne, hÃ´pitaux universitaires Paris-Seine-Saint-Denis, Assistance publique HÃ´pitaux de Paris, Bobigny, F-93000, France; 5Inserm, UMR 1162, GÃ©nomique fonctionnelle des tumeUrs solides, Paris, F-75010, France; 6Centre de Ressources Biologiques BB-0033-00027, HÃ´pital Avicenne, hÃ´pitaux universitaires Paris-Seine-Saint-Denis, Assistance publique HÃ´pitaux de Paris, Bobigny, F-93000, France; 7Service dâanatomie et cytologie pathologique, HÃ´pital Avicenne, hÃ´pitaux universitaires Paris-Seine-Saint-Denis, Assistance publique HÃ´pitaux de Paris, Bobigny, F-93000, France&ast;These authors contributed equally to this workCorrespondence: Erwan Guyot, HÃ´pitaux Universitaires Paris Seine-Saint-Denis, Laboratoire Biochimie-Pharmacologie et Biologie MolÃ©culaire, 125 Rue de Stalingrad, Bobigny, 93000, France, Tel +33 1 48 95 56 29, Fax +33 1 48 95 56 27, Email erwan.guyot@aphp.frPurpose: Sulfatase 2 (SULF2) is an enzyme related to heparan sulfate modifications. Its expression, as for some heparan sulfate proteoglycans expression, has been linked to hepatocellular carcinoma (HCC) at mRNA level and immunohistochemistry staining on biopsy samples. This study aims to evaluate the prognostic value of serum levels of SULF2 in patients with alcoholic cirrhosis with or without HCC.Patients and Methods: Two hundred and eighty-seven patients with alcoholic cirrhosis were enrolled in this study: 164 without HCC, 57 with early HCC, and 66 with advanced HCC at inclusion. We analyzed the association between SULF2 serum levels and prognosis using KaplanâMeier method and univariate and multivariate analysis using a Cox model.Results: Child-Pugh C Patients have higher serum levels of SULF2 than Child-Pugh A patients. Serum levels of SULF2 were also higher in patients with advanced HCC compared with the other groups. In patients with advanced HCC, high serum levels of SULF2 were associated with less favorable overall survival. Combination of SULF2 with Glypican 3 (GPC3) and Syndecan 1 (SDC1) serum levels enhanced the ability to discriminate worst prognostic in advanced HCC.Conclusion: SULF2 along with GPC3 and SDC1 serum levels have been shown to be associated with a prognostic value in advanced HCC.Keywords: sulfatase 2, proteoglycans, prognosis, hepatocellular carcinoma, cirrhosis
Published: 2022

35. Baseline ALBI score and early variation of serum AFP predicts outcomes in patients with HCC treated by atezolizumab-bevacizumab

Author: Claudia Campani, Jessica Bamba‐Funck, Bertille Campion, Sabrina Sidali, Lorraine Blaise, Nathalie Ganne‐Carrié, Alix Demory, Olivier Sutter, Edouard Larrey, Manon Evain, Haroun Ghannouchi, Mathilde Wagner, Fabio Marra, Angela Sutton, Manon Allaire, and Jean‐Charles Nault
Subjects: Hepatology
Abstract: The combination of atezolizumab and bevacizumab (AtezoBev) is the current first-line treatment for patients with hepatocellular carcinoma (HCC). Our aim was to evaluate the prognostic role of alpha-foetoprotein (AFP) early response and its combination with albumin-bilirubin (ALBI) in these patients.Patients with HCC under AtezoBev with AFP 20 ng/ml were included in three centres. The optimal threshold of AFP variation after 3 weeks of treatment was identified for overall survival (OS) and radiological response (RR) using RECIST 1.1 and mRECIST and its ability to predict progression-free survival (PFS) and OS was tested using univariate and multivariate analysis in derivation and validation cohorts.Seventy-five patients with AFP values20 ng/ml were included. Fifty-eight patients were male with a median age of 63.5 years; 73% had cirrhosis and HCC stage was classified as BCLC B (18.7%) or C (81.3%). In the derivation cohort (n = 38), a decline in AFP ≥ 20% at 3 weeks (AFP early response) was associated with RR using mRECIST criteria (OR: 13.09 95% CI: 1.44-19.34 p = .02), PFS (HR: 0.42; 95% CI: 0.19-0.93, p = .03) and OS (HR: 0.35; 95% CI: 0.15-0.83, p = .01). AFP early response was confirmed as predictor of RR (p = .02 for mRECIST) and OS (p = .03) in the validation cohort (n= 37). In the whole cohort, the combination of ALBI and AFP early response was significantly associated with OS (p = .046) and PFS (p = .012) with a poor prognosis in patients belonging to the ALBI2-AFP non-responders class.AFP early response at 3 weeks predicts oncological outcomes in HCC patients treated with AtezoBev and combination with ALBI grade refines prognostic discrimination.
Published: 2022

36. Low alcohol consumption influences outcomes in individuals with alcohol-related compensated cirrhosis in a French multicenter cohort

Author: Alexandre Louvet, Valérie Bourcier, Isabelle Archambeaud, Louis d’Alteroche, Cendrine Chaffaut, Frédéric Oberti, Christophe Moreno, Dominique Roulot, Thông Dao, Romain Moirand, Jean-Charles Duclos-Vallée, Odile Goria, Eric Nguyen-Khac, Stanislas Pol, Nicolas Carbonell, Jérôme Gournay, Laure Elkrief, Isabelle Fouchard-Hubert, Sylvie Chevret, Nathalie Ganne-Carrié, null Louis d’Alteroche, Jean-Marie Péron, Victor de Lédinghen, Violaine Ozenne, Jean Henrion, Albert Tran, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, CHU Lille, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Erasme [Bruxelles], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pontchaillou [Rennes], Hôpital Paul Brousse, Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Amiens-Picardie, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIRRAL group, École pratique des hautes études (EPHE), CHU Trousseau [Tours], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), and Hopital Saint-Louis [AP-HP] (AP-HP)
Subjects: liver decompensation, [PHYS]Physics [physics], Alcohol-related liver disease, Cirrhosis, Hepatology, Recurrence, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background and aims: The harmful impact of heavy alcohol recurrence has been confirmed in patients with alcohol-related cirrhosis although this is based on old studies. The drivers of long-term outcome still need to be clearly investigated.Method: All patients with biopsy-proven compensated alcohol-related cirrhosis included in the CIRRAL cohort (22 centers) were prospectively studied. Prognostic variables of survival and liver event-free survival were assessed using multivariable Cox models with stepwise selection. The prognostic impact of alcohol recurrence during follow-up (computed in glasses-years in the same way as pack-years for tobacco) was assessed using a time-dependent covariable.Results: From 2010 to 2016, 650 patients were included. The median age at baseline was 58.4 years old, 67.4% were men and the median BMI was 27.8 kg/m2, 63.8% had a history of liver decompensation, and 70.2% had discontinued alcohol. At 5 years, 30.9% of abstinent patients developed recurrence and this risk was higher in patients with a history of drug abuse and in those with shorter alcohol discontinuation times. Median survival was 97 months. Age, alcohol consumption at baseline, platelet count and Child-Pugh score >5 were associated with overall and liver event-free survival on multivariate analysis. Alcohol consumption during follow-up of more than 25 glasses-year was independently associated with lower survival and with a trend toward significant liver event-free survival, but the risk increased from 1 glass-year, though not significantly. Simon & Makuch plots confirm the benefit of no alcohol consumption (
Published: 2022
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37. Non-invasive diagnosis and follow-up of chronic infection with hepatitis B virus

Author: Vincent Leroy, Stéphane Chevaliez, Marie Decraecker, Dominique Roulot, Jean Nana, Tarik Asselah, Xavier Causse, David Durantel, Vincent Thibaut, Nathalie Ganne-Carrié, Christophe Bureau, Victor de Lédinghen, Marc Bourlière, 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), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Grenoble Alpes (UGA), CHU Grenoble, Hôpital Beaujon [AP-HP], Centre Hospitalier Régional d'Orléans (CHRO), Centre de Recherche en Cancérologie de Lyon (UNICANCER/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), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Saint-Joseph [Marseille], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Humans, Hepatology, MESH: Hepatitis B, Chronic, [SDV]Life Sciences [q-bio], Gastroenterology, MESH: Follow-Up Studies, ab, MESH: DNA, Viral, MESH: Hepatitis B Surface Antigens, MESH: Hepatitis B virus, MESH: RNA, MESH: Liver Neoplasms, MESH: Persistent Infection, MESH: Liver Cirrhosis, MESH: Carcinoma, Hepatocellular, MESH: Hepatitis B e Antigens
Abstract: Diagnosis of chronic hepatitis B virus (HBV) infection, initial staging of infection and monitoring of treated and untreated patients are mainly based on clinical, biological and imaging criteria allowing a complete non-invasive management for the majority of patients. Along to the conventional virological tools, rapid diagnostic tests and blotting paper tests for HBV DNA are validated alternatives. After diagnosis, the initial work-up should include HIV, HCV and HDV serologies, HBeAg status, and HBsAg and HBV DNA quantification. Assessment of severity (inflammation and fibrosis) is based on ALT serum levels and non-invasive evaluation of liver fibrosis by elastography or blood tests, which must be interpreted cautiously using specific cutoffs and taking into account ALT levels. Taken together, these parameters allow disease classification and treatment decision. Decision of hepatocellular carcinoma screening by ultra-sound every six months may be difficult in non-cirrhotic patients and the use of risk-scores such as PAGE-B is encouraged. Chronic HBV infection often has a dynamic and often unpredictable profile and regular monitoring is mandatory. In untreated patients, regular (3-12 months) follow-up should include ALT and HBV DNA serum levels. Periodical HBsAg quantification and non-invasive evaluation of liver fibrosis may refine disease outcome and prognosis. In treated patients, checking efficacy is mainly based on HBV DNA negativity. In patients with advanced fibrosis, evolution of liver stiffness can be useful for portal hypertension evaluation, but its improvement should not be considered to stop hepatocellular carcinoma screening. Finally, new parameters (HBV RNA, HBcrAg) are promising but their use is still restricted for research.
Published: 2022
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38. Non-invasive diagnosis and follow-up of portal hypertension

Author: Victor de Lédinghen, Thomas Sersté, Christophe Bureau, Marika Rudler, Dominique Thabut, Nathalie Ganne-Carrié, Delphine Weil, Charlotte Bouzbib, Laurent Castera, Christophe Cassinotto, Frédéric Oberti, M. Bourlière, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Pierre, Service d’Hépato-Gastroentérologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Joseph [Marseille], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: medicine.medical_specialty, Cirrhosis, Portal venous pressure, [SDV]Life Sciences [q-bio], MESH: Elasticity Imaging Techniques, Chronic liver disease, Gastroenterology, Asymptomatic, MESH: Esophageal and Gastric Varices, Internal medicine, Medicine, In patient, MESH: Hypertension, Portal, MESH: Humans, Hepatology, medicine.diagnostic_test, business.industry, Non invasive, MESH: Follow-Up Studies, medicine.disease, Endoscopy, MESH: Endoscopy, Gastrointestinal, Portal hypertension, medicine.symptom, MESH: Liver Cirrhosis, business
Abstract: Compensated advanced chronic liver disease (cACLD) describes the spectrum of advanced fibrosis/cirrhosis in asymptomatic patients at risk of developing clinically significant portal hypertension (CSPH, defined by a hepatic venous pressure gradient (HVPG) 10 mmHg). Patients with cACLD are at high risk of liver-related morbidity and mortality. In patients at risk of chronic liver disease, cACLD is strongly suggested by a liver stiffness (LSM) value >15 kPa or clinical/biological/radiological signs of portal hypertension, and ruled out by LSM 150 G/L (favourable Baveno VI criteria) at the time of diagnosis. There is no non-invasive method alternative for oeso-gastroduodenal endoscopy in patients with unfavourable Baveno criteria (liver stiffness 20 kPa or platelet count 50 G/l). Platelet count and liver stiffness measurements must be performed once a year in patients with cACLD with favourable Baveno VI criteria at the time of diagnosis. A screening oeso-gastroduodenal endoscopy is recommended if Baveno VI criteria become unfavourable.
Published: 2022
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39. Health-related quality of life in locally advanced hepatocellular carcinoma treated by either radioembolisation or sorafenib (SARAH trial)

Author: Helena Pereira, Mohamed Bouattour, Marco D. Burgio, Eric Assenat, Jules Grégory, Jean-Pierre Bronowicki, Gilles Chatellier, Valérie Vilgrain, Elisabeth Delhom-Christol, Marjolène Fourcade, Boris Guiu, Alina Diana Ilonca, Julie Lonjon, Georges-Philippe Pageaux, Mohamed Abdel-Rehim, Wassim Allaham, Laurent Castera, Arnaud Dieudonné, Rachida Lebtahi, Maxime Ronot, Annie Sibert, Hélène Chor, Julie Devictor, Hélène Barraud, Christophe Bazin, Laetitia Imbert, Valérie Laurent, Elodie Mathias, Carine Chagneau-Derrode, Christelle Gallais, Rémy Perdrisot, Christine Silvain, Jean Pierre Tasu, Patrick Borentain, Bardia Farman, René Gerolami, Olivier Mundler, Jean-Francois Seitz, Vincent Vidal, Christophe Aubé, Francis Bouchet, Antoine Bouvier, Olivier Couturier, Frédéric Oberti, Laurent Vervueren, Isabelle Brenot-Rossi, Julien Darreon, Jean Luc Raoul, Anthony Sarran, Julia Chalaye, Charlotte Costentin, Emmanuel Itti, Hicham Kobeiter, Alain Luciani, Hélène Masset, René Adam, Maïté Lewin, Didier Samuel, Julien Edeline, Etienne Garin, Sophie Laffont, Yan Rolland, Isabelle Archambeaud, Thomas Carlier, Thomas Eugene, Eric Frampas, Christophe Cassinotto, Martine Guyot, Jean-Baptiste Hiriart, Bruno Lapuyade, Karine Tendero, Julien Vergniol, Philippe Bachellier, Julien Détour, Bernard Duclos, Michel Greget, Francois Habersetzer, Alessio Imperiale, Elise Enderlin, Philippe Merle, Agnès Rode, Julie Morvan, Eric Nguyen-Khac, Antoine Talbot, Thierry Yzet, Guillaume Baudin, Patrick Chevallier, Abakar Mahamat, Fabien Maurel, Thierry Piche, Micheline Razzouk, Patrick Hillon, Romaric Loffroy, Michel Toubeau, Julie Vincent, Jean-Marc Vrigneaud, Gabriele Barabino, Nadia Bouarioua, Muriel Cuilleron, Marie Ecochard, Nathalie Prevot-Bitot, Evelyne Rousset, Vincent Leroy, Ghislaine Reboulet, Julie Roux, Christian Sengel, Valérie Bourcier, Nathalie Ganne-Carrie, Olivier Seror, Sylvie Costo, Thông Dao, Cédric Desmonts, Jean-Pierre Pelage, Didier Defez, Jérôme Dumortier, Francesco Giammarile, Pierre-Jean Valette, Michela Bernardini, Nadia Ghazar, Olivier Pellerin, Julien Taieb, Pierre Weinmann, Alexandra Heurgue-Berlot, Claude Marcus, Daniele Sommacale, Maria-Angéla Castilla-Lièvre, Aurélie Forbes, Sophie Maitre, Lysiane Marthey, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), and Université de Bourgogne (UB)-Université de Bourgogne (UB)
Subjects: Male, Sorafenib, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Tare weight, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Locally advanced, Quality of life, Internal medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Social functioning, Health related quality of life, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, Embolization, Therapeutic, digestive system diseases, Confidence interval, Oncology, Hepatocellular carcinoma, Quality of Life, Female, business, medicine.drug
Abstract: Background The aim of this ancillary study of the SARAH trial is to compare health-related quality of life (HRQoL) in patients with locally advanced or inoperable hepatocellular carcinoma (HCC) treated with transarterial radioembolisation (TARE) or sorafenib. Methods This study included randomised patients who received either TARE or at least one dose of sorafenib with no major deviation in the protocol and who had at least one QoL follow-up assessment in addition to the baseline evaluation. QoL was assessed from the date of randomisation using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, until disease progression or other reasons for stopping study participation. Data were analysed using linear mixed and time-dependent models. Results A total of 285 patients were included (122 and 163, in the TARE and sorafenib groups, respectively). Questionnaire completion rates were similar (77.5% versus 80.4%, in the TARE and sorafenib groups, respectively, p = 0.25). Longitudinal HRQoL analysis showed a significant treatment and time effects for fatigue and global health status, and significant treatment, time and treatment by time interaction effects for appetite loss, diarrhoea and social functioning. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7–4.3) versus 2.6 months (95% CI 2.0–3.0) in the TARE and sorafenib groups, respectively. Conclusions HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. These data could be used to optimise management of patients with advanced or inoperable HCC.
Published: 2021
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40. Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: The SURFASA score

Author: Olivier Chazouillères, Florent Artru, Eleonora De Martin, Philippe Mathurin, Camille Besch, Christophe Duvoux, François Durand, Odile Goria, Hélène Fontaine, Hélène Agostini, Isabelle Ollivier-Hourmand, Noemi Reboux, Olivier Roux, Filomena Conti, Nathalie Ganne-Carrié, Didier Samuel, Georges-Philippe Pageaux, Philippe Ichai, Marilyne Debette-Gratien, Christine Silvain, Alexandra Heurgue, Jean-Marie Peron, Sylvie Radenne, Jérôme Dumortier, Audrey Coilly, Pauline Houssel-Debry, Sandrine Barge, Marc Bourlière, Pascal Potier, Jean-Charles Duclos-Vallée, Vincent Di Martino, Mylène Sebagh, and Victor de Ledinghen
Subjects: 0301 basic medicine, medicine.medical_specialty, Multivariate analysis, Hepatology, medicine.drug_class, Bilirubin, business.industry, medicine.medical_treatment, Odds ratio, Autoimmune hepatitis, Liver transplantation, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, Internal medicine, medicine, Corticosteroid, 030211 gastroenterology & hepatology, Prospective cohort study, business, Survival rate
Abstract: Background & Aims In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated. Methods This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3–D0)/D0. Results A total of 128 patients were included, with a median age of 52 (39–62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23–21.06; p Conclusion In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort. Lay summary The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
Published: 2021
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41. Body weight changes and duration of estrogen exposure modulate the evolution of hepatocellular adenomas after contraception discontinuation

Author: Alix Demory, Jean‐Marie Péron, Julien Calderaro, Janick Selves, Fatima‐Zohra Mokrane, Giuliana Amaddeo, Valérie Paradis, Marianne Ziol, Olivier Sutter, Lorraine Blaise, Nathalie Ganne‐Carrié, Valérie Vilgrain, François Cauchy, Jessica Zucman‐Rossi, Maxime Ronot, and Jean‐Charles Nault
Subjects: Hepatology
Abstract: The natural history of hepatocellular adenomas (HCAs) remains to be better described, especially in nonresected patients. We aim to identify the predictive factors of HCA evolution after estrogen-based contraception discontinuation.We retrospectively included patients with a histological diagnosis of HCA from three centers. Clinical, radiological, and pathological data were collected to identify predictive factors of radiological evolution per Response Evaluation Criteria in Solid Tumors, version 1.1, and occurrence of complications (bleeding, malignant transformation). We built a score using variables that modulate estrogen levels: body mass index and duration of estrogen-based contraception. An external cohort was used to validate this score. 183 patients were included in the cohort, including 161 women (89%) using estrogen-based contraception for a median of 12 years. Thirty percent of patients had at least one HNF1A-inactivated HCA, 45.5% at least one inflammatory HCA, and 11% at least one HCA with activation of β-catenin (bHCA). Twenty-one symptomatic bleedings (11%) and eleven malignant transformations (6%) occurred. Ages 37 years old (p = 0.004) and HCA 5 cm at imaging were independently associated with symptomatic bleeding (p = 0.003), whereas a bHCA was associated with malignant transformation (p 0.001). After a median follow-up of 5 years, radiological regression was observed in 31%, stabilization in 47%, and progression in 22% of patients. Weight loss was associated with regression (p 0.0001) and weight gain with progression (p = 0.02). The estrogen exposure score predicted radiological regression (odds ratio, 2.33; confidence interval 95%, 1.29-4.19; p = 0.005) with a linear relationship between the rate of estrogen exposure and the probability of regression. This result was confirmed in an external cohort of 72 female patients (p = 0.003).Weight variation is strongly associated with radiological evolution after oral contraception discontinuation. A score of estrogen exposure, easily assessable in clinical practice at diagnosis, predicts regression of HCA.
Published: 2022

42. Implementing advanced practice nursing in France: A country-wide survey 2 years after its introduction

Author: Julie Devictor, Espérie Burnet, Tatiana Henriot, Anne Leclercq, Nathalie Ganne‐Carrie, Kelley Kilpatrick, and Ljiljana Jovic
Subjects: General Nursing
Abstract: To examine the characteristics of the first Advanced Practice Nurses in France and to compare the French model to international standards.Common barriers and facilitators to their integration in healthcare provision have been identified internationally. In France, the legislative framework was introduced in 2016, and the first graduates entered the workforce in 2019.The French model was examined in comparison with Hamric's conceptual framework and to the International Council of Nurses' guidelines and definitions. A cross-sectional survey was also conducted, using three self-administered online questionnaires. Two were distributed to 2019 and 2020 graduates and a third to the accredited programme directors. The characteristics of advanced practice nursing graduates were described and compared based on employment status and field of practice (primary vs secondary/tertiary care).Although the French model of advanced practice nursing meets Hamric's primary criteria and core competencies, it does not differentiate between Nurse Practitioner and Clinical Nurse Specialist roles. Of the 320 students enrolled in one of the 11 accredited training programmes 165 participated in the survey. Mean age was 40, and mean prior nursing experience was 15 years. By February 2021, 30% of respondents were still employed as Registered Nurses. Barriers to practice included insufficient income generation (primary care), the lack of position creation (secondary/tertiary care), the physician-dependent patient referral process and delays in prescription credentials approval.The implementation of advanced practice nursing in France faces several barriers. Legislative adjustments and greater financial incentives to practice seem warranted.as in other countries, France introduced advanced practice nursing to respond to the Public Health challenge of improving access to quality health care in the context of increasing chronic disease prevalence and limited resource allocation. Facilitating its integration in the healthcare provision landscape seems paramount.
Published: 2022

43. Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus

Author: Thierry Poynard, Guillaume Lassailly, Juliette Foucher, Manh-Thông Dao, Xavier Duval, Isabelle Hourmand-Ollivier, Séverine Hommel, Vincent Di Martino, Pierre-Henri Bernard, Dominique Larrey, Nathalie Boyer, Anais Labrunie, Marc Bardou, Paul Carrier, Marilyne Debette-Gratien, Marie Essig, Eric Nguyen-Khac, Armand Abergel, Victor de Ledinghen, Véronique Loustaud-Ratti, Claire Vanlemmens, Nathalie Ganne-Carrié, Anne Gervais, Jean-Baptiste Hiriart, Fouchard-Hubert Isabelle, Christine Aurières, Pauline Pinet, Thierry Thevenot, Jérémie Jacques, Philippe Mathurin, Dominique Thabut, Christophe Renou, Daniel Cohen, Marianne Maynard, Valérie Canva, Julien Vergniol, Bertrand Hanslik, Anaïs Brayette, Sophie Alain, Matthieu Schnee, Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Pôle Universitaire d’Addictologie en Limousin, CH Esquirol [Limoges] (CH Esquirol), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-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), Plate forme de bioinformatique et biostatistique (CEBIMER), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), 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), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Limoges], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hepatology, Hopital, Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Service d'Hépato-gastro-entérologie et oncologie digestive (CHU de Bordeaux), CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Paris School of Economics (PSE), Université Paris 1 Panthéon-Sorbonne (UP1)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Paris Jourdan Sciences Economiques (PJSE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Normandie Université (NU), Service d'Hépatologie [CHRU Besançon], Hôpital Haut-Lévêque [CHU Bordeaux], Hôpital Claude Huriez [Lille], CHU Lille, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Université Paris Cité (UPCité), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Hôpital Saint-Éloi [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Hepatitis B virus, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Renal function, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Nucleoside analogues, Internal medicine, medicine, Cumulative incidence, Renal insufficiency, education, education.field_of_study, Hepatology, business.industry, Proximal tubulopathy, Incidence (epidemiology), Hazard ratio, Entecavir, Hepatitis B, medicine.disease, 030220 oncology & carcinogenesis, Prospective Study, 030211 gastroenterology & hepatology, business, Biomarkers, medicine.drug
Abstract: International audience; BACKGROUND The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. Multiple early markers are available, but no consensus exists on their use. AIM To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated vs untreated hepatitis B virus (HBV)-monoinfected patients. METHODS A prospective, non-randomized, multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted. The patients were separated into three groups: Naive, starting entecavir (ETV) treatment, or starting tenofovir disoproxil (TDF) treatment. Data on the early markers of SPT, the eGFR and phosphatemia, were collected quarterly. SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%. The prevalence and cumulative incidence of SPT at month 24 (M24) were calculated. Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests, whereas chi-squared or Fisher's exact tests were used to analyze qualitative data. Multivariate analyses were used to adjust for any potential confounding factors. RESULTS Of the 196 patients analyzed, 138 (84 naive, 28 starting ETV, and 26 starting TDF) had no SPT at inclusion. At M24, the prevalence of SPT was not statistically different between naive and either treated group (21.1% vs 30.7%, P < 0.42 and 50.0% vs 30.7%, P = 0.32 for ETV and TDF, respectively); no patient had an eGFR lower than 50 mL/min/1.73 m(2) or phosphatemia less than 0.48 mmoL/L. In the multivariate analysis, no explanatory variables were identified after adjustment. The cumulative incidence of SPT over 24 mo (25.5%, 13.3%, and 52.9% in the naive, ETV, and TDF groups, respectively) tended to be higher in the TDF group vs the naive group (hazard ratio: 2.283, P = 0.05). SPT-free survival at M24 was 57.6%, 68.8%, and 23.5% for the naive, ETV, and TDF groups, respectively. The median survival time without SPT, evaluated only in the TDF group, was 5.9 mo. CONCLUSION The prevalence and incidence of SPT was higher in TDF-treated patients compared to naive patients. SPT in the naive population suggests that HBV can induce renal tubular toxicity.
Published: 2020
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44. Individual and population screening of varices needing treatment by a simple, safe and accurate test

Author: Federico Ravaioli, Arthur Berger, Oana Farcau, Antonio Colecchia, Horia Stefanescu, Camille Candillier, Pierre Nahon, Christophe Bureau, Nathalie Ganne-Carriè, Annalisa Berzigotti, Victor de Ledinghen, Salvatore Petta, Paul Calès, null multicentric groups, null Bologna, null Cluj, null Bondy, null Toulouse, null Bern, null Bordeaux, and null Palermo
Subjects: Hepatology, Gastroenterology
Published: 2023
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45. International multicenter validation of GES score for HCC risk stratification in chronic hepatitis C patients

Author: Shiha, Gamal, primary, Soliman, Reham, additional, Mikhail, Nabiel N. H., additional, Carrat, Fabrice, additional, Azzi, Jessica, additional, Nathalie, Ganne‐Carrié, additional, Toyoda, Hidenori, additional, Uojima, Haruki, additional, Nozaki, Akito, additional, Takaguchi, Koichi, additional, Hiraoka, Atsushi, additional, Atsukawa, Masanori, additional, Abe, Hiroshi, additional, Matsuura, Kentaro, additional, Mikami, Shigeru, additional, Watanabe, Tsunamasa, additional, Tsuji, Kunihiko, additional, Ishikawa, Toru, additional, Suri, Vithika, additional, Osinusi, Anu, additional, Ni, Liyun, additional, Zou, Jun, additional, Sarin, Shiv Kumar, additional, Kumar, Manoj, additional, Jalal, Prasun Kumar, additional, Hashim, Mahmoud A., additional, Hassan, Manal, additional, Lopez, Sonia Alonso, additional, Bañares, Rafael, additional, Ahumada, Adriana M., additional, Mousa, Nasser Hamed, additional, Eslam, Mohammed, additional, and Waked, Imam, additional
Published: 2022
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46. Comparison of screening strategies with two new tests to score and diagnose varices needing treatment

Author: Paul Calès, Federico Ravaioli, Arthur Berger, Oana Farcau, Davide Festi, Horia Stefanescu, Carole Vitellius, Pierre Nahon, Christophe Bureau, Nathalie Ganne-Carriè, Annalisa Berzigotti, Victor de Ledinghen, Salvatore Petta, Calès, Paul, Ravaioli, Federico, Berger, Arthur, Farcau, Oana, Festi, Davide, Stefanescu, Horia, Vitellius, Carole, Nahon, Pierre, Bureau, Christophe, Ganne-Carriè, Nathalie, Berzigotti, Annalisa, de Ledinghen, Victor, and Petta, Salvatore
Subjects: Liver Cirrhosis, Hepatology, Non-invasive test, Platelet Count, Gastroenterology, Esophageal and Gastric Varices, Varicose Veins, Elastometry, Non-alcoholic Fatty Liver Disease, Oesophageal varice, Screening, Elasticity Imaging Techniques, Humans, Portal hypertension, Retrospective Studies
Abstract: Background and aims: We aimed to improve non-invasive screening of varices needing treatment (VNT) and compare different screening strategies. Methods: 2,290 patients with chronic liver disease were included in a retrospective study. Etiologies were: virus: 50.0%, NAFLD: 29.5%, alcohol: 20.5%, VNT: 14.9%. Test descriptors were performance (spared endoscopy) and safety (missed VNT). VNT tests were evaluated according to their safety levels either for individual screening (95% negative predictive value (NPV)), population screening (95% sensitivity) or undifferentiated screening (100% sensitivity/NPV) without missed VNT. The tests provided three categories: missed VNT
Published: 2022
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47. Non-invasive diagnosis and follow-up of chronic infection with Hepatitis C Virus

Author: Stéphane Chevaliez, Sarah Shili-Masmoudi, Lucile Moga, Isaac Ruiz, Nathalie Ganne-Carrié, Albert Tran, M. Bourlière, Christophe Bureau, Victor de Lédinghen, Alain Luciani, Hôpital l'Archet, Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Henri Mondor, 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), Hôpital Avicenne [AP-HP], Université Sorbonne Paris Nord, Hôpital Rangueil, CHU Toulouse [Toulouse], Hôpital Saint-Joseph [Marseille], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Malbec, Odile
Subjects: Liver Cirrhosis, HBsAg, medicine.medical_specialty, Hepatitis C virus, [SDV]Life Sciences [q-bio], Hepacivirus, medicine.disease_cause, Gastroenterology, Virus, Fibrosis, Internal medicine, medicine, Humans, Hepatology, business.industry, Liver Diseases, virus diseases, Hepatitis C, Chronic, medicine.disease, Hepatitis C, digestive system diseases, [SDV] Life Sciences [q-bio], Chronic infection, Liver, HBeAg, Hepatocellular carcinoma, Elasticity Imaging Techniques, Portal hypertension, Persistent Infection, business, Follow-Up Studies
Abstract: Diagnosis of chronic hepatitis B virus (HBV) infection, initial staging of infection and monitoring of treated and untreated patients are mainly based on clinical, biological and imaging criteria allowing a complete non-invasive management for the majority of patients. Along to the conventional virological tools, rapid diagnostic tests and blotting paper tests for HBV DNA are validated alternatives. After diagnosis, the initial work-up should include HIV, HCV and HDV serologies, HBeAg status, and HBsAg and HBV DNA quantification. Assessment of severity (inflammation and fibrosis) is based on ALT serum levels and non-invasive evaluation of liver fibrosis by elastography or blood tests, which must be interpreted cautiously using specific cut-offs and taking into account ALT levels. Taken together, these parameters allow disease classification and treatment decision. Decision of hepatocellular carcinoma screening by ultra-sound every six months may be difficult in non-cirrhotic patients and the use of risk-scores such as PAGE-B is encouraged. Chronic HBV infection often has a dynamic and often unpredictable profile and regular monitoring is mandatory. In untreated patients, regular (3-12 months) follow-up should include ALT and HBV DNA serum levels. Periodical HBsAg quantification and non-invasive evaluation of liver fibrosis may refine disease outcome and prognosis. In treated patients, checking efficacy is mainly based on HBV DNA negativity. In patients with advanced fibrosis, evolution of liver stiffness can be useful for portal hypertension evaluation, but its improvement should not be considered to stop hepatocellular carcinoma screening. Finally, new parameters (HBV RNA, HBcrAg) are promising but their use is still restricted for research.
Published: 2022
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48. Clinical, histological and molecular profiling of different stages of alcohol-related liver disease

Author: Meritxell Ventura-Cots, Josepmaria Argemi, Patricia D Jones, Carolin Lackner, Mohamed El Hag, Juan G Abraldes, Edilmar Alvarado, Ana Clemente, Samhita Ravi, Antonio Alves, Mohamed Alboraie, Jose Altamirano, Sergio Barace, Francisco Bosques, Robert Brown, Juan Caballeria, Joaquin Cabezas, Sofia Carvalhana, Helena Cortez-Pinto, Adilia Costa, Delphine Degré, Carlos Fernandez-Carrillo, Nathalie Ganne-Carrie, Guadalupe Garcia-Tsao, Joan Genesca, John Koskinas, Nicolas Lanthier, Alexandre Louvet, Juan José Lozano, Michael R Lucey, Steven Masson, Philippe Mathurin, Nahum Mendez-Sanchez, Rosa Miquel, Christophe Moreno, Taofic Mounajjed, Gemma Odena, Won Kim, Pau Sancho-Bru, R Warren Sands, Justyna Szafranska, Laurine Verset, Bern Schnabl, Christine Sempoux, Vijay Shah, Debbie Lindsay Shawcross, Rudolf E Stauber, Beate K Straub, Elizabeth Verna, Dina Tiniakos, Eric Trépo, Victor Vargas, Càndid Villanueva, John T Woosley, Marianne Ziol, Sebastian Mueller, Peter Stärkel, Ramon Bataller, Repositório da Universidade de Lisboa, UCL - (SLuc) Service de gastro-entérologie, and UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie
Subjects: Hepatitis, Alcoholic, alcohol, Gastroenterology, Histopathology, Alcoholic liver disease, Fibrosis, Liver, alcohol-induced injury, gene expression, histopathology, Humans, Prospective Studies, Gene expression, Alcohol, Alcohol-induced injury, Retrospective Studies, alcoholic liver disease
Abstract: © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ., Objective: Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking. Design: Two large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed. Results: Age and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism. Conclusions: Despite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients., This work was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA 1U01AA021908-01, 1U01AA020821 and P50AA011999) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK P30DK120531 and P30DK120515). PSwas supported by Fondo de Investigación Sanitaria Carlos III, cofinanced by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, 'Una manera de hacer Europa' PI17/00673; PI20/00765 and Miguel Servet, CPII16/0004. MV-C is a recipient of the Juan Rodés JR19/00015. JA is a recipient of a grant from Agencia Estatal de Salud (PI20/01663).
Published: 2022

49. Common genetic variation in alcohol-related hepatocellular carcinoma: a case-control genome-wide association study

Author: Eric Trépo, Stefano Caruso, Jie Yang, Sandrine Imbeaud, Gabrielle Couchy, Quentin Bayard, Eric Letouzé, Nathalie Ganne-Carrié, Christophe Moreno, Abderrahim Oussalah, Cyrille Féray, Jean Frédéric Blanc, Bruno Clément, Patrick Hillon, Jérôme Boursier, Valérie Paradis, Julien Calderaro, Viviane Gnemmi, Jean-Charles Nault, Jean-Louis Guéant, Jacques Devière, Isabelle Archambeaud, Carole Vitellius, Bruno Turlin, Jean-Pierre Bronowicki, Thierry Gustot, Angela Sutton, Marianne Ziol, Pierre Nahon, Jessica Zucman-Rossi, Clément Meiller, Qian Cao, Théo Z. Hirsch, Sandra Rebouissou, Delphine Degré, Lukas Otero Sanchez, Nicolas Rosewick, Eric Quertinmont, Mireille Desille-Dugast, Muriel François-Vié, Cécile Moins, Emmanuelle Leteurtre, Guillaume Lassailly, Massih Ningarhari, Emmanuel Boleslawski, Vanessa Cottet, Université libre de Bruxelles (ULB), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), People's Hospital of Peking University (PKUPH), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Paul Brousse, CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre de Ressources Biologiques Santé (CRB Santé), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Beaujon [AP-HP], 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), Hôpital Henri Mondor, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Hôtel-Dieu de Nantes, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpitaux Universitaires Paris Seine-Saint-Denis [Sevran] (HUP2SD), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), BB-0033-00027, H2020 Marie Skłodowska-Curie Actions, MSCA, University Hospitals, UH: NCT03311152, Bpifrance, Agence Nationale de la Recherche, ANR: ANR-11-LABX-0021, Institut National de la Santé et de la Recherche Médicale, Inserm, Assistance Publique - Hôpitaux de Paris, AP-HP, Ligue Contre le Cancer, Fondation de France, Institut National Du Cancer, INCa, Université Libre de Bruxelles, Conseil régional de Bourgogne-Franche-Comté, Korean Association for the Study of the Liver, KASL, GENTHEP Consortium: Clément Meiller, Qian Cao, Théo Z Hirsch, Sandra Rebouissou, Delphine Degré, Lukas Otero Sanchez, Nicolas Rosewick, Eric Quertinmont, Mireille Desille-Dugast, Muriel François-Vié, Cécile Moins, Emmanuelle Leteurtre, Guillaume Lassailly, Massih Ningarhari, Emmanuel Boleslawski, Vanessa Cottet, ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011), École pratique des hautes études (EPHE), Jonchère, Laurent, Laboratoires d'excellence - Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - - Lipstic2011 - ANR-11-LABX-0021 - LABX - VALID, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), Faculté de Médecine [Bruxelles] [ULB], Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)], Biochimie – Biologie moléculaire et Nutrition [CHRU Nancy], Institut National de la Santé et de la Recherche Médicale [INSERM], Centre Hépato-Biliaire [Hôpital Paul Brousse] [CHB], Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn], Lipides - Nutrition - Cancer [Dijon - U1231] [LNC], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand [CHU Dijon], Centre Hospitalier Universitaire d'Angers [CHU Angers], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques [HIFIH], Université Paris-Est Créteil Val-de-Marne - Paris 12 [UPEC UP12], Institut Mondor de Recherche Biomédicale [IMRB], Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], Université Sorbonne Paris Nord, Centre Hospitalier Régional Universitaire de Nancy [CHRU Nancy], Nutrition-Génétique et Exposition aux Risques Environnementaux [NGERE], Nutrition, Métabolismes et Cancer [NuMeCan], Laboratoire de Recherche Vasculaire Translationnelle [LVTS (UMR_S_1148 / U1148)], Hôpital Européen Georges Pompidou [APHP] [HEGP], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI], and Equipe EPICAD (LNC - U1231)
Subjects: Adult, Male, Carcinoma, Hepatocellular, Genotype, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Polymorphism, Single Nucleotide, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Wnt3A Protein, Humans, Genetic Predisposition to Disease, Aged, Aged, 80 and over, Liver Neoplasms, Genetic Variation, Middle Aged, Wnt Proteins, [SDV] Life Sciences [q-bio], Oncology, Case-Control Studies, Phospholipases A2, Calcium-Independent, Female, Alcohol-Related Disorders, Acyltransferases, Genome-Wide Association Study
Abstract: International audience; Background: Hepatocellular carcinoma is a frequent consequence of alcohol-related liver disease, with variable incidence among heavy drinkers. We did a genome-wide association study (GWAS) to identify common genetic variants for alcohol-related hepatocellular carcinoma. Methods: We conducted a two-stage case-control GWAS in a discovery cohort of 2107 unrelated European patients with alcohol-related liver disease aged 20–92 years recruited between Oct 22, 1993, and March 12, 2017. Cases were patients with alcohol-related hepatocellular carcinoma diagnosed by imaging or histology. Controls were patients with alcohol-related liver disease without hepatocellular carcinoma. We used an additive logistic regression model adjusted for the first ten principal components to assess genetic variants associated with alcohol-related hepatocellular carcinoma. We did another analysis with adjustment for age, sex, and liver fibrosis. New candidate associations (pandlt;1 × 10−6) and variants previously associated with alcohol-related hepatocellular carcinoma were evaluated in a validation cohort of 1933 patients with alcohol-related liver disease aged 29–92 years recruited between July 21, 1995, and May 2, 2019. We did a meta-analysis of the two case–control cohorts. Findings: The discovery cohort included 775 cases and 1332 controls. Of 7 962 325 variants assessed, we identified WNT3A-WNT9A (rs708113; p=1·11 × 10−8) and found support for previously reported regions associated with alcohol-related hepatocellular carcinoma risk at TM6SF2 (rs58542926; p=6·02 × 10−10), PNPLA3 (rs738409; p=9·29 × 10−7), and HSD17B13 (rs72613567; p=2·49 × 10−4). The validation cohort included 874 cases and 1059 controls and three variants were replicated: WNT3A-WNT9A (rs708113; p=1·17 × 10−3), TM6SF2 (rs58542926; p=4·06 × 10−5), and PNPLA3 (rs738409; p=1·17 × 10−4). All three variants reached GWAS significance in the meta-analysis: WNT3A-WNT9A (odds ratio 0·73, 95% CI 0·66–0·81; p=3·93 × 10−10), TM6SF2 (1·77, 1·52–2·07; p=3·84×10−13), PNPLA3 (1·34, 1·22–1·47; p=7·30 × 10−10). Adjustment for clinical covariates yielded similar results. We observed an additive effect of at-risk alleles on alcohol-related hepatocellular carcinoma. WNT3A-WNT9A rs708113 was not associated with liver fibrosis. Interpretation: WNT3A-WNT9A is a susceptibility locus for alcohol-related hepatocellular carcinoma, suggesting an early role of the Wnt–β-catenin pathway in alcohol-related hepatocellular carcinoma carcinogenesis.
Published: 2022
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50. Non-invasive diagnosis and follow-up of rare genetic liver diseases

Author: Rodolphe Sobesky, Olivier Guillaud, Charlotte Bouzbib, Philippe Sogni, Aurélia Poujois, France Woimant, Jean Charles Duclos-Vallée, Marc Bourlière, Victor de Lédinghen, Nathalie Ganne-Carrié, Christophe Bureau, Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), National reference Centre for Wilson's Disease [Paris] (CRMR Wilson), Service de neurologie [Univ. Paris VII], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Hôpital Saint-Joseph [Marseille], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Avicenne [AP-HP], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), École pratique des hautes études (EPHE), and Malbec, Odile
Subjects: medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Disease, Gastroenterology, Liver disease, Rare Diseases, Hepatolenticular Degeneration, Fibrosis, Internal medicine, alpha 1-Antitrypsin Deficiency, medicine, Humans, Hepatology, medicine.diagnostic_test, business.industry, Cystic fibrosis screening, Non invasive, medicine.disease, Molecular analysis, [SDV] Life Sciences [q-bio], Liver, Liver biopsy, business, Biomarkers, Copper, Follow-Up Studies
Abstract: International audience; Rare genetic liver diseases can result in multi-systemic damage, which may compromise the patient's prognosis. Wilson's disease and alpha-1 antitrypsin deficiency must be investigated in any patient with unexplained liver disease. Cystic fibrosis screening of new-borns is now implemented in most high-prevalence countries. The diagnosis of these diseases can be strongly suggested with specific non-invasive tests. Molecular analysis gene for these diseases is long and tedious but is recommended to confirm the diagnosis and help for the family screening. Liver biopsy is not systematic and is discussed when it helps diagnosis. Currently, for these three diseases, non-invasive fibrosis markers could identify patients with risk of cirrhosis and complications. Rare genetic liver diseases can result in multi-systemic damage, which may compromise the patient's prognosis. Wilson's disease, must be investigated in any patient with unexplained liver disease and/or unexplained neurological or neuropsychiatric disorders. The diagnosis is based on a combination of clinical, biological features, including copper balance. The exchangeable copper/total copper ratio is a new sensible and specific biological marker, useful for the diagnosis of the disease. Timely diagnosis and treatment will prevent serious complications from the disease. Neurological evaluation and familial screening are essential in patients with Wilson's disease.
Published: 2022
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