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Liver angiogenesis as a risk factor for hepatocellularcarcinoma development in hepatitis C virus cirrhotic patients

World Journal of Gastroenterology 2007年第37期13卷 5009-5014页

作者： Roberto Mazzanti Luca Messerini Camilla E Comin Lorenzo Fedeli nathalie gannè-carrie Michel Beaugrand Dipartimento di Medicina Interna Sezione di Oncologia Medica Centro di Eccellenza DENOthe Azienda Ospedaliero-Universitaria Careggi Istituto Toscano Tumori Università degli Studi di Firenze Florence Italy Dipartimento di Patologia Umana ed Oncologia Istituto Toscano Tumori Università degli Studi di Firenze Florence Italy nathalie gannè-carrie Michel Beaugrand Service d'Hepato-Gastroenterologie Hopital Jean Verdier Assistance Publique-Hopitaux de Paris et UFR SMBH-Universite Paris XIII Bondy France nathalie gannè-carrie Michel Beaugrand Service d’Hepato-Gastroenterologie Hopital Jean Verdier Assistance Publique-Hopitaux de Paris et UFR SMBH-Universite Paris XIII Bondy France

AIM： To evaluate the predictive value of hepatocyte proliferation and hepatic angiogenesis for the occurrence of Hepatocellular carcinoma （HCC） in hepatitis C virus （HCV） cirrhotic patients.METHODS： One hundred-five patients （69 males, 36 females; age range, 51-90 year; median 66 year） with biopsy proven HCV cirrhosis were prospectively monitored for HCC occurrence for a median time of 64 too. Angiogenesis was assessed by using microvessel density （MVD）, hepatocyte turnover by MIB1 and PCNA indexes at inclusion in liver biopsies.RESULTS： Forty six patients （43.8%） developed HCC after a median time of 55 （6-120） mo while 59 （56.2%） did not. Patients were divided into two groups according to the median value of each index. The difference between patients with low （median MVD = 3; range 0-20） and high （median MVD = 7; range 1-24） MVD was statist（caUy s（gn（ficant （χ^2= 22.06; P 〈 0.0001） wh（ch was not the case for MIB1 or PCNA （MIB-I： χ^2 = 1.41; P = 0.2351; PCNA： χ^2 = 1.27; P = 0.2589）. The median MVD was higher in patients who developed HCC than in those who did not. HOe-free interval was significantly longer in patients with the MVD ≤ 4 （P = 0.0006）. No relationship was found between MIB1 or PCNA and MVD （MIB-1 r^2 = 0.00007116, P = 0.9281; PCNA： P =0.001950; P = 0.6692）. MVD only was able to predict the occurrence of HCC in these patients. Among other known risk factors for HCC, only male sex was statistically associated with an increased risk. CONCLUSION： Liver angiogenesis has a role for in HCV- related liver carcinogenesis and for defining patients at higher risk.

关键词： Liver cancer Hepatitis C virus Angiogenesis Proliferating cell nuclear antigen

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Impact of sarcopenia on tumor response and survival outcomes in patients with hepatocellular carcinoma treated by trans-arterial (chemo)-embolization

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World Journal of Gastroenterology 2022年第36期28卷 5324-5337页

作者： 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 Jean-Charles Nault Univ.Grenoble-Alpes Grenoble 38058France Department of Hepatology Gastroenterology and Digestive OncologyCHU Grenoble AlpesGrenoble 38043France Institute for Advanced Biosciences INSERM U1209/CNRS UMR 5309Grenoble 38043France Department of Radiology CHU Grenoble AlpesGrenoble 38043France Department of Radiology CHU Avicenne-APHPBobigny 93000France Functional Genomics of Solid Tumors Laboratory Centre de Recherche des Cordeliers-INSERM UMR 1138InsermUniversitéParisParis 75006France Unitéde Formation et de Recherche SantéMédecine et Biologie Humaine UniversitéParis NordParis 93430France Service d'Epidémiologie et Evaluation Médicale CHU Grenoble AlpesGrenoble 38043France Department of Hepatology CHU Avicenne-APHPBobigny 93000France

BACKGROUND At the diagnosis of hepatocellular carcinoma(HCC),more than 90%of HCC patients present cirrhosis,a clinical condition often associated to *** is an indirect marker of malnutrition assessable on computed tomography(CT).AIM To evaluate the prognostic value of sarcopenia in patients with HCC treated by trans-arterial(chemo)-*** Patients with HCC treated by a first session of trans-arterial(chemo)embolization and an available CT scan before treatment were *** was assessed using skeletal muscle index at baseline and at the first radiological *** response was recorded after the first session of treatment using *** Of 225 patients treated by trans-arterial bland embolization(n=71)or trans-arterial chemoembolization(n=154)for HCC between 2007 and 2013,Barcelona Clinic of Liver Cancer stage was A,B,and C in 27.5%,55%,and 16.8%of cases,*** was present in 57.7%of the *** with sarcopenia presented a higher rate of progressive disease(19%vs 8%,P=0.0236),a shorter progression-free survival(8.3 vs 13.2 mo,P=0.0035),and a shorter median overall survival(19.4 mo vs 35.5 mo,P=0.0149)compared with non-sarcopenic ***,patients whose sarcopenia appeared after first transarterial treatment had the worst prognosis(P=0.0004).CONCLUSION Sarcopenia is associated with tumor progression and poor survival outcomes after trans-arterial(chemo)-embolization for HCC.

关键词： Hepatocellular carcinoma Transarterial chemoembolization Bland embolization Sarcopenia Skeletal muscle index

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Elucidating regulatory processes of intense physical activity by multi-omics analysis

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Military Medical Research 2024年第4期11卷 479-499页

作者： Ernesto S.Nakayasu Marina A.Gritsenko Young-Mo Kim Jennifer E.Kyle Kelly G.Stratton carrie D.Nicora nathalie Munoz Kathleen M.Navarro Daniel Claborne Yuqian Gao Karl K.Weitz Vanessa L.Paurus Kent J.Bloodsworth Kelsey A.Allen Lisa M.Bramer Fernando Montes Kathleen A.Clark Grant Tietje Justin Teeguarden Kristin E.Burnum-Johnson Biological Sciences Division Pacific Northwest National LaboratoryRichlandWA 99352USA Environmental and Molecular Sciences Division Pacific Northwest National LaboratoryRichlandWA 99352USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthWestern States DivisionDenverCO 80204USA Computational Analytics Division Pacific Northwest National LaboratoryRichlandWA 99352USA National Security Directorate Pacific Northwest National LaboratoryRichlandWA 99352USA Los Angeles County Fire Department Los AngelesCA 90063USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthRespiratory Health DivisionMorgantownWV 26505USA Environmental and Molecular Toxicology Oregon State UniversityCorvallisOR 97331USA

Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,military,and sports.A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work ***:To study regulatory processes in intense physical activity simulating real-life conditions,we performed a multi-omics analysis of 3 biofluids(blood plasma,urine,and saliva)collected from 11 wildland firefighters before and after a 45 min,intense exercise *** profiles ***-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics ***:Our multi-omics analysis identified and quantified 3835 proteins,730 lipids and 182 metabolites combining the 3 different types of *** blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy *** urine analysis showed a strong,concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites,reabsorption of nutrients and maintenance of fluid *** saliva,we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides.A systematic literature review identified 6 papers that support an altered susceptibility to respiratory ***:This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility,suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

关键词： Multi-omics analysis Intense exercise Human performance Biofluids Metabolism Immunity

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

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World Journal of Hepatology 2020年第12期12卷 1326-1340页

作者： Anais Brayette Marie Essig Paul carrier Marilyne Debette-Gratien Anais Labrunie Sophie Alain Marianne Maynard nathalie ganne-carrie Eric Nguyen-Khac Pauline Pinet Victor De Ledinghen Christophe Renou Philippe Mathurin Claire Vanlemmens Vincent Di Martino Anne Gervais Juliette Foucher Fouchard-Hubert Isabelle Julien Vergniol Isabelle Hourmand-Ollivier Daniel Cohen Xavier Duval Thierry Poynard Marc Bardou Armand Abergel Manh-Thong Dao Thierry Thevenot Jean-Baptiste Hiriart Valerie Canva Guillaume Lassailly Christine Aurières nathalie Boyer Dominique Thabut Pierre-Henri Bernard Matthieu Schnee Dominique Larrey Bertrand Hanslik Severine Hommel Jeremie Jacques Veronique Loustaud-Ratti U1248 INSERM Department of Hepatology and GastroenterologyUniv.LimogesCHU LimogesLimoges F-87000France U1248 INSERM Department of Nephrology and TransplantationCHU LimogesLimoges F-87000France Department of Center of Epidemiology Biostatistics and Research MethodologyCHU LimogesLimoges F-87000France U1092 INSERM Department of VirologyCHU LimogesLimoges F-87000France Department of Hepatology Croix-Rousse University Hospital of LyonLyon 69004France Department of Hepatology Jean Verdier University Hospital of BondyBondy 93140France Department of Hepato-Gastroenterology Amiens University HospitalAmiens 80054France Department of Infectious Diseases CHU LimogesLimoges F-87000France Department of Hepatology Haut Leveque HospitalBordeaux University HospitalPessac 33604France Department of Gastroenterology Hyeres HospitalHyeres 83407France Department of Hepato-Gastroenterology Claude Huriez University HospitalLille 59037France Department of Hepatology Jean Minjoz University HospitalBesançon 25030France Department of Infectious Diseases Bichat University HospitalParis 75018France Department of Hepatology University Hospital of AngersAngers 49933France Department of Hepato-Gastroenterology and Nutrition University Hospital of CaenCaen 14033France Department of General Medecine University Hospital of CaenCaen 14000France Department of Hepatology La Pitié-Salpêtrière University HospitalParis 75651France Department of Hepatology and Gastroenterology Dijon University HospitalDijon 21079France Department of Hepatology and Gastroenterology Estaing University HospitalClermont Ferrand 63003France Department of Hepatology Beaujon University HospitalClichy 92110France Department of Hepatology Saint-AndréUniversity HospitalBordeaux 33000France Department of Hepatology and Gastroenterology La Roche-Sur-Yon Hospital CenterLa Roche-Sur-Yon 85000France Department of Hepatology and Gastroenterology University Hospital of MontpellierMontpellier 34295France Department of Addictology Hospita

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 *** early markers are available,but no consensus exists on their *** 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 *** A prospective,non-randomized,multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was *** patients were separated into three groups:Naïve,starting entecavir(ETV)treatment,or starting tenofovir disoproxil(TDF)*** on the early markers of SPT,the eGFR and phosphatemia,were collected *** 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 *** data were analyzed using analyses of variance or Kruskal-Wallis tests,whereas chi-squared or Fisher’s exact tests were used to analyze qualitative *** analyses were used to adjust for any potential confounding *** Of the 196 patients analyzed,138(84 naïve,28 starting ETV,and 26 starting TDF)had no SPT at *** M24,the prevalence of SPT was not statistically different between naïve 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 m²or phosphatemia less than 0.48 mmoL/*** the multivariate analysis,no explanatory variables were identified after *** cumulative incidence of SPT over 24 mo(25.5%,13.3%,and 52.9%in the naïve,ETV,and TDF groups,respectively)tended to be higher in the TDF group vs the naïve group(hazard ratio:2.283,P=0.05).SPT-free survival at M24 was 57.6%,68.8%,and 23.5%for the naïve,ETV,and TD

关键词： Hepatitis B virus Proximal tubulopathy Biomarkers Renal insufficiency Nucleoside analogues

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