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Impact of switching from ranibizumab to aflibercept on the number of intravitreous injection and follow up visit in wet AMD:results of real life ELU study

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International Journal of Ophthalmology(English edition) 2020年第2期13卷 252-256页

作者： Frederic Queguiner Kristina Bezirganyan Jean Christophe Courjaret Laurence Curel Guillaume Penaranda Maud Righini Chossegros Ophthalmology and Clinical Research Departments Hopital Saint JosephMarseille F-13008France Biostatistics Department Alphabio LaboratoryMarseille F-13003France

●AIM:To study if one of the two molecules could lead to a lower number of follow up visits and intra-vitreous injection(IVI)with the same efficacy.●METHODS:ELU(or"elected"in French)study is a retrospective study conducted in real life in patients presenting suboptimal response after ranibizumab IVI(phase 1)and secondary switched to aflibercept(phase 2).The number of follow up visits and IVI were compared in both *** acuity(VA)evolution and"switching"reasons were secondary analyzed.●RESULTS:We retrospectively included data of 33 patients(38 eyes)with age-related macular degeneration(AMD;mean age:77±7.7 y).The number of monthly follow up visits[median(Q1;Q3)]:was significantly lower with aflibercept(phase 2),respectively 1.0(0.81;1.49)visits in phase 1,versus 0.79(0.67;0.86)visits in phase *** median number of monthly IVI also significantly decreased in phase 2,respectively 0.67(0.55;0.90)IVI in phase 1,versus 0.55(0.45;0.67)IVI in phase *** mean VA evolution(VA final-VA initial)was similar in both phases,(P>0.05).Whatever the reason for"switching"(loss of efficacy,tachyphylaxis,tolerance problems),there was no incidence on VA evolution over the time.●CONCLUSION:Our results show that switching from ranibizumab to aflibercept in"suboptimal"patients significantly reduce the number of follow up visits and IVI,with a comparable *** decrease in visit number could improve patients’quality of life and reduce surgical risk by reducing the number of injections.

关键词： wet age-related macular degeneration anti-VEGF aflibercept ranibizumab follow up visit intravitreal injection visual acuity

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Second-line therapy for advanced hepatocellular carcinoma with regorafenib or cabozantinib:Multicenter French clinical experience in real-life after matching

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World Journal of Gastrointestinal Oncology 2022年第8期14卷 1510-1527页

作者： Xavier Adhoute Marie De Matharel Laurent Mineur Guillaume Pénaranda Dann Ouizeman Clemence Toullec Albert Tran Paul Castellani Armelle Rollet Valérie Oules HervéPerrier Si Nafa Si Ahmed Marc Bourliere Rodolphe Anty Department of Gastroenterology and Hepatology Hôpital Saint-JosephMarseille 13000France Department of Gastroenterology and Hepatology Hôpital Universitaire de l’ArchetNice 06000France Department of Oncology Institut Sainte-CatherineAvignon 84000France Department of Biostatistics AlphaBio LaboratoryMarseille 13000France

BACKGROUND Starting a second-line systemic treatment for hepatocellular carcinoma(HCC)is a common *** only therapeutic options in France are two broadspectrum tyrosine kinase inhibitors(TKIs),regorafenib(REG)and cabozantinib(CBZ),but no comparative real-life studies are *** To evaluate the progression-free survival(PFS)of patients treated with REG or CBZ,we investigated the disease control rate(DCR),overall survival(OS),and safety of both *** identify the variables associated with disease progression over *** A retrospective multicenter study was performed on the clinical data of patients attending one of three referral centers(Avignon,Marseille,and Nice)between January 2017 and March 2021 using propensity score *** and OS were assessed using the Kaplan-Meier *** analysis(MA)of progression risk factors over time was performed in matched-pair *** Fifty-eight patients 68(62-74)years old with HCC,Barcelona clinic liver cancer(BCLC)B/C(86%),Child-Pugh(CP)-A/B(24%)received REG for 3.4(1.4-10.5)mo as second-line *** patients 68(60-73)years,BCLC B/C(75%),CP-A/B(25%)received CBZ for 3.7(1.8-4.9)mo after first-line treatment with sorafenib[3(2-4)(CBZ)vs 4(2.9-11.8)mo(REG),P=0.0226].Twenty percent of patients received third-line *** matching,PFS and DCR were not significantly different after a median follow-up of 6.2(2.7-11.7)mo(REG)vs 5.2(4-7.2)mo(CBZ),P=*** was no difference in grade 3/4 toxicities,dose reductions,or *** OS of CP-A patients was 8.3(5.2-24.8)vs 4.9(1.6-11.7)mo(CP-B),P=*** MA of risk factors for progression over time identified C-reactive protein(CRP)>10 mg/L,neutrophil-to-lymphocyte ratio(NLR)>3,and aspartate aminotransferase(AST)>45 IU as predictive *** This multicenter indirect comparative study found no significant difference in PFS between REG and CBZ as second-line therapy for advanced *** levels of inflam

关键词： Hepatocellular carcinoma Regorafenib Cabozantinib C-reactive protein Neutrophillymphocyte ratio

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Usefulness of the MESH score in a European hepatocellular carcinoma cohort

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World Journal of Hepatology 2017年第15期9卷 711-714页

作者： Xavier Adhoute Guillaume Pénaranda Jean-Luc Raoul Marc Bourlière Department of Hepato-Gastroenterology Hopital Saint-Joseph Marseille alphabio laboratory Marseille Department of Hepato-Gastroenterology and Digestive Oncology Institut Paoli-Calmette Marseille

The Barcelona Clinic Liver Cancer classification is the most widely-used hepatocellular carcinoma(HCC) staging system because it is simple,precise and linked to a treatment algorithm based on randomized *** each group includes a broad spectrum of tumors,with limited therapeutic options,particularly for intermediate and advanced ***,different additional scoring systems have been proposed to refine the prognosis and/or to improve the *** until now,there is no *** et al proposes a new scoring system,based on a large HCC cohort,with patients at different stages,treated using diverse *** score includes six parameters used in current *** is simple to calculate,reliable,with an ability to predict survival superior to other systems,which also works with our European HCC *** MESH score may be especially useful to differentiate subgroups with different prognosis for each treatment modality.

关键词： Hepatocellular carcinoma Barcelona Clinic Liver Cancer Scoring system MESH NIACE

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Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma:Real-life Data on Liver Disease,Treatment and Prognosis

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1106-1117页

作者： Xavier Adhoute Olivia Pietri Guillaume Pénaranda Thomas Wolf Patrick Beaurain Olivier Monnet Arthur Laquière Justine Bonomini Frédéric Neumann Olivier Levrel Jean-Pascal Buono Xavier Hanna Paul Castellani HervéPerrier Marc Bourliere Rodolphe Anty Department of Gastroenterology and Hepatology Hôpital Saint-JosephMarseilleFrance Department of Biostatistics AlphaBio-Biogroup LaboratoryMarseilleFrance Department of Radiology Hôpital Saint-JosephMarseilleFrance Department of Clinical Research Hôpital Saint-JosephMarseilleFrance Medipath EguillesFrance Department of Hepatobiliary Surgery Hôpital Saint-JosephMarseilleFrance Department of Gastroenterology and Hepatology Hôpital Universitaire de l’ArchetNiceFrance

Background and Aims:Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA)have common features and *** real-life study investigated their characteristics,treatment modalities,and ***:This retrospective comparative study was performed in 1,075 patients seen at one tertiary center between January 2008 and December *** survival(OS)was estimated by the Kaplan-Meier *** of iCCAs after histological and radiological review,and molecular profiling was ***:HCCs patients were more likely to have early-stage disease than iCCA *** patients were more likely to be female,especially those patients without cirrhosis(43%vs.17%).Cirrhosis was prominent among HCC patients(89%vs.34%),but no difference in underlying liver disease among cirrhotic patients was *** of HCC patients was 18.4(95%CI:6.4,48.3)months,that of iCCA patients was 7.0(95%CI:3.4,20.1)*** of Barcelona Clinic Liver Cancer C HCC patients was 7.8(95%CI:4.3,14.2)months,that of advanced/metastatic iCCA patients was 8.5(95%CI:5.7,12.3)*** patients treated with sorafenib,OS was longer in HCC patients who received subsequent tyrosine kinase inhibitor *** significant OS difference was found between iCCA patients with and without cirrhosis or according to histological subtype.A targetable molecular alteration was detected in 50%of the iCCA ***:In this French series,cirrhosis was common in iCCA,which showed etiological factors comparable to those of HCC,implying a distinct oncogenic *** entities had a dismal prognosis at advanced ***,systemic therapies sequencing in HCC and molecular profiling in iCCA offer new insights.

关键词： Intrahepatic cholangiocarcinoma Hepatocellular carcinoma Cirrhosis NASH Oncogenic alterations

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Increased fibrosis progression rates in hepatitis C patients carrying the prothrombin G20210A mutation

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World Journal of Gastroenterology 2011年第45期17卷 5007-5013页

作者： Nitsan Maharshak Philippe Halfon Varda Deutsch Hava Peretz Shlomo Berliner Sigal Fishman Shira Zelber-Sagi Uri Rozovski Moshe Leshno Ran Oren Department of Gastroenterology and Liver diseases Tel Aviv Sourasky Medical Center aff iliated to the Sackler School of Medicine Tel Aviv University Department of Virology Laboratoire Alphabio 23 Rue de Friedland Hpital Ambroise Paré The Hematology Institute Tel Aviv Sourasky Medical Center affi liated to the Sackler School of Medicine Tel Aviv University Clinical Biochemistry laboratory Tel Aviv Sourasky Medical Center affiliated to the Sackler School of Medicine Tel Aviv University Internal Medicine "E" Tel Aviv Sourasky Medical Center affi liated to the Sackler School of Medicine Tel Aviv University

AIM: To examine whether hepatitis C virus (HCV)-infected patients who carry hypercoagulable mutationssuffer from increased rates of liver fi brosis. METHODS: We analyzed DNA samples of 168 HCV patients for three common hypercoagulable gene mutations: prothrombin 20210 (PT20210), factor V Leiden (FV Leiden) and methylene tetrahydrofolate reductase (MTHFR). The patients were consecutively recruited as part of the prospective "Fibroscore Study" in France. The effect of the various mutations on the rate of fi-brosis was analyzed statistically and was correlated with epidemiological, clinical and biochemical data such as grade and stage of liver biopsies, patients' risk factors for liver cirrhosis, and timing of infection. RESULTS: Fifty two of the patients were categorized as "fast fi brosers" and 116 as "slow fi brosers"; 13% of the "fast fi brosers" carried the PT20210 mutation as compared with 5.5% of the "slow fi brosers", with an odds ratio of 4.76 (P = 0.033; 95% CI: 1.13-19.99) for "fast" liver fibrosis. Carriage of MTHFR or FV Leiden mutations was not associated with enhanced liver fi brosis. CONCLUSION: Carriage of the PT20210 mutation is related to an increased rate of liver fi brosis in HCV patients.

关键词： Hepatitis C virus Liver fi brosis Hyperco-agulation Prothrombin 20210

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Recommendations for the use of chemoembolization in patients with hepatocellular carcinoma: Usefulness of scoring system?

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World Journal of Hepatology 2015年第3期7卷 521-531页

作者： Xavier Adhoute Guillaume Penaranda Paul Castellani Herve Perrier Marc Bourliere Department of Hepatology Hopital Saint-Joseph 13285 Marseille France Laboratoire alphabio Hopital Europeen 13003 Marseille France

Several hepatocellular carcinoma(HCC) staging systems have been established, and a variety of countryspecific treatment strategies are also proposed. The barcelona- clinic liver cancer(BCLC) system is the most widely used in Europe. The Hong Kong liverCancer is a new prognostic staging system; it might become the reference system in Asia. Transarterial chemoembolization(TACE) is the most widely used treatment for HCC worldwide; but it showed a benefit only for intermediate stage HCC(BCLC B), and there is still no consensus concerning treatment methods and treatment strategies. In view of the highly diverse nature of HCC and practices, a scoring system designed to assist with decision making before the first TACE is performed or prior to repeating the procedure would be highly useful.

关键词： Hepatocellular carcinoma Transarterial chemoembolization Barcelona Clinic Liver Cancer Prognostic scoring systems

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Expected outcomes and patients’selection before chemoembolization—“Six-and-Twelve or Pre-TACE-Predict”scores may help clinicians:Real-life French cohorts results

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World Journal of Clinical Cases 2021年第18期9卷 4559-4572页

作者： Xavier Adhoute Edouard Larrey Rodolphe Anty Patrick Chevallier Guillaume Penaranda Albert Tran Jean-Pierre Bronowicki Jean-Luc Raoul Paul Castellani HervéPerrier Olivier Bayle Olivier Monnet Bernard Pol Marc Bourliere Department of Gastroenterology and Hepatology Hôpital Saint-JosephMarseille 13008France Department of Gastroenterology and Hepatology Hôpital Universitaire de l’ArchetNice 06000France Department of Radiology Hôpital Universitaire de l’ArchetNice 06000France Statistics Department AlphaBio LaboratoryMarseille 13003France Department of Gastroenterology and Hepatology Centre Hospitalo-Universitaire de NancyVandoeuvre les Nancy 54511France Department of Medical Oncology Institut de Cancérologie de l’OuestSite de NantesNantes 44805France Department of Radiology Hôpital Saint-JosephMarseille 13008France Department of Hepatobiliary Surgery Hôpital Saint-JosephMarseille 13008France

BACKGROUND Careful selection of hepatocellular carcinoma(HCC)patients prior to chemoembolization treatment is a daily reality,and is even more necessary with new available therapeutic options in *** propose two new models to better stratify patients and maximize clinical benefit:“6 and 12”and“pre/post-TACE-predict”(TACE,transarterial chemoembolization).METHODS We evaluated and compared their performance in predicting overall survival with other systems{Barcelona Clinic Liver Cancer(BCLC),Albumin-Bilirubin(ALBI)and NIACE[Number of tumor(s),Infiltrative HCC,alpha-fetoprotein,Child-Pugh(CP),and performance status]}in two HCC French cohorts of different stages enrolled between 2010 and *** The cohorts included 324 patients classified as BCLC stages A/B(cohort 1)and 137 patients classified as BCLC stages B/C(cohort 2).The majority of the patients had cirrhosis with preserved liver function.“Pre-TACE-predict”and“6 and 12”models identified three distinct categories of patients exhibiting different prognosis in cohort ***,their prognostic value was no better than the BCLC system or NIACE *** function based on CP and ALBI grades significantly impacted patient ***,the“post-TACE-predict”model had a higher predictive value than other *** stratification ability as well as predictive performance of these new models in an intermediate/advanced stage population was less efficient(cohort 2).CONCLUSION The newly proposed“Pre-TACE-predict”and“6 and 12”models offer an interesting stratification into three categories in a recommended TACE population,as they identify poor candidates,those with partial control and durable *** models'contribution was reduced in a population with advanced stage HCCs.

关键词： Hepatocellular carcinoma Transarterial chemoembolization Pre-TACEpredict Six-and-twelve Barcelona Clinic Liver Cancer Prognosis

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“Six-and-twelve” score for outcome prediction of hepatocellular carcinoma following transarterial chemoembolization. In-depth analysis from a multicenter French cohort

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World Journal of Hepatology 2020年第8期12卷 525-532页

作者： Xavier Adhoute Guillaume Pénaranda Jean-Luc Raoul Jean-Pierre Bronowicki Rodolphe Anty MarcBourlière Department of Gastroenterology and Hepatology Hôpital Saint-JosephMarseille 13008France alphabio laboratory Marseille 13003France Department of Medical Oncology Institut de Cancérologie de l'OuestNantes 44805France Department of Gastroenterology and Hepatology Centre Hospitalo-Universitaire deNancy 54511France Department of Gastroenterology and Hepatology Hôpital Universitaire de l’ArchetNice 06200France

The“six-and-twelve”(6&12)score is a new hepatocellular carcinoma(HCC)prognostic index designed for recommended transarterial chemoembolization(TACE)*** and easy to use by the sum of tumor size(cm)and number,this model identifies three groups with different survival time(the sum is≤6;or>6 but≤12;or>12);a survival benefit with TACE can be expected for HCC patients with a score not exceeding ***,Wang ZW et al showed that the“6&12”model was the best system correlated with radiological response after the first ***,we wanted to assess its survival prediction ability as well as its prognostic value and compared it to other systems(Barcelona Clinic Liver Cancer,Hong Kong Liver Cancer(HKLC)staging,Albumin-Bilirubin grade,tumor nodularity,infiltrative nature of the tumor,alpha-fetoprotein,Child-Pugh class,and Performance Status score,Cancer of the Liver Italian Program,Model to Estimate Survival for HCC scores,up-to-seven criteria)different from Wang ZW et al study in a multicenter French cohort of HCC including only recommended TACE candidates retrospectively *** previously demonstrated,we show that the"6&12”score can classify survival within this French cohort,with a prognostic value comparable to that of other systems,except HKLC *** importantly,the“6&12”score simplicity and ability in patients’stratification outperform other systems for a routine clinical practice.

关键词： Hepatocellular carcinoma Transarterial chemoembolization “Six-and-twelve”score Prognosis Albumin-Bilirubin grade Tumor nodularity,infiltrative nature of the tumor,alpha-fetoprotein,Child-Pugh class,and performance status score

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Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model

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World Journal of Hepatology 2016年第21期8卷 902-914页

作者： Sylvie Lagaye Sonia Brun Jesintha Gaston Hong Shen Ruzena Stranska Claire Camus Clarisse Dubray Géraldine Rousseau Pierre-Philippe Massault Jerome Courcambeck Firas Bassisi Philippe Halfon Stanislas Pol Institut Pasteur INSERM Institut Cochin INSERM U1016CNRS UMR8104Universite Paris Descartes(UMR S1016) Genoscience Pharma KU Leuven Rega Institute Laboratoire alphabio APHP Groupe Hospitalier La Pitie Salpe-triereService de Chirurgie digestive et Hepato bilio pancreatique APHP Groupe Hospitalier CochinService de Chirurgie digestiveHepato-biliaire et Endocrinienne Universite Paris Descartes APHP Groupe Hospitalier CochinUnite d’Hepatologie Institut Pasteur Departement de Recherche TranslationnelleINSERM

AIM: To evaluate the antiviral potency of a new antihepatitis C virus(HCV) antiviral agent targeting the cellular autophagy machinery. METHODS: Non-infected liver slices, obtained from human liver resection and cut in 350 μm-thick slices(2.7 × 106 cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant(multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with GNS-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription- polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays. RESULTS: The antiviral efficacy of a new antiviral drug, GNS-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dosedependent manner. At day 6 post-treatment, GNS-396 EC50 was 158 nmol/L without cytotoxic effect(compared to hydroxychloroquine EC50 = 1.17 μmol/L).CONCLUSION: Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative GNS-396 as antiviral could inhibit HCV infection in a dosedependent manner without cytotoxic effect.

关键词： Host antiviral therapy Hepatitis C virus Tissue culture Autophagy Quinoline derivative

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