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Fibrosis assessment using Fibro Meter combined to first generation tests in hepatitis C

World Journal of Hepatology 2017年第6期9卷 310-317页

作者： Maria Chiara Chindamo Jerome Boursier Ronir Raggio Luiz Isabelle Fouchard-Hubert Vera Lúcia Nunes Pannain Joao Marcello de Araújo Neto Henrique Sérgio Moraes Coelho Renata de Mello Perez Paul Calès Cristiane Alves Villela-Nogueira Departament of Internal Medicine Federal University of Rio de Janeiro Department of Hepatology University Hospital hifih laboratory UPRES 3859SFR 4208Bretagne Loire University Institute of Public Health Studies Federal University of Rio de Janeiro Departament of Pathology Federal University of Rio de Janeiro Gastroenterology Department University of the State of Rio de Janeiro D’Or Institute for Research and Education

AIMTo evaluate the performance of FibroMeterVirus3G combined to the first generation tests aspartate aminotransferase-to-platelet ratio index (APRI) or Forns index to assess significant fibrosis in chronic hepatitis C (CHC). METHODSFirst generation tests APRI or Forns were initially applied in a derivation population from Rio de Janeiro in Brazil considering cut-offs previously reported in the literature to evaluate significant fibrosis. FibroMeterVirus3G was sequentially applied to unclassified cases from APRI or Forns. Accuracy of non-invasive combination of tests, APRI plus FibroMeterVirus3G and Forns plus FibroMeterVirus3G was evaluated in the Brazilian derivation population. APRI plus FibroMeterVirus3G combination was validated in a population of CHC patients from Angers in France. All patients were submitted to liver biopsy staged according to METAVIR score by experienced hepatopathologists. Significant fibrosis was considered as METAVIR F ≥ 2. The fibrosis stage classification was used as the reference for accuracy evaluation of non-invasive combination of tests. Blood samples for the calculation of serum tests were collected on the same day of biopsy procedure or within a maximum 3 mo interval and stored at -70 °C. RESULTSSeven hundred and sixty CHC patients were included (222 in the derivation population and 538 in the validation group). In the derivation population, the FibroMeterVirus3G AUROC was similar to APRI AUROC (0.855 vs 0.815, P = 0.06) but higher than Forns AUROC (0.769, P Virus3G cut-off to discriminate significant fibrosis was 0.61 (80% diagnostic accuracy; 75% in the validation population, P = 0.134). The sequential combination of APRI or Forns with FibroMeterVirus3G in derivation population presented similar performance compared to FibroMeterVirus3G used alone (79% vs 78% vs 80%, respectively, P = 0.791). Unclassified cases of significant fibrosis af

关键词： Chronic hepatitis C Fibrosis Liver biopsy Non-invasive methods FibroMeterVirus3G Combination algorithms

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FibroMeters:诊断肝纤维化的血液学检测指标组合(英文)

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传染病信息 2013年第3期26卷 134-140页

作者： Paul Calès Jérme Boursier Frédéric Oberti Isabelle Hubert Yves Gallois Marie Christine Rousselet Valérie Moal Laurent Macchi Alain Chevailler Julien Chaigneau Gilles Hunault hifih laboratory LUNAM University Hepato-gastroenterology department University Hospital Biochemistry laboratory Hepato-gastroenterology department University Hospital Pathology department University Hospital Hematology laboratory University Hospital Immunology laboratory University Hospital

FibroMeters是具有多项特异性的诊断肝纤维化的血液学检测指标组合,其3个主要诊断目标为显著肝纤维化、肝硬化以及肝纤维化的定量,并由专业系统针对不同病因进行调整从而保证获得准确的结果。因此,主要存在 6 种不同的 FibroMeters:即... 详细信息

FibroMeters是具有多项特异性的诊断肝纤维化的血液学检测指标组合,其3个主要诊断目标为显著肝纤维化、肝硬化以及肝纤维化的定量,并由专业系统针对不同病因进行调整从而保证获得准确的结果。因此,主要存在 6 种不同的 FibroMeters:即针对肝纤维化的3种主要病因慢性病毒性肝炎、酒精性肝病和非酒精性脂肪性肝病的肝纤维化分期和肝纤维化定量。以肝组织病理学方法诊断肝纤维化程度进行对照,FibroMeters 表现出非常高的诊断准确率,是惟一能100%正确区分丙型肝炎患者不伴有肝纤维化或伴有肝硬化的检测方法。在适用性方面,FibroMeters 对于显著肝纤维化的 90%预测值高于其他血清学检测方法。使用包括 7 类内容在内的详细的肝纤维化分期方法,87%的丙型肝炎患者可以获得准确的肝纤维化分期。在实际工作条件下,FibroMeters 重复性高于肝组织病理结果,也高于超声弹性检测。因诊断性能表现非常稳定,FibroMeters 在不同的中心都是稳健的检测方法。目前可选择的检测有:针对肝硬化诊断的 CirrhoMeter,在一项丙型肝炎肝硬化患者的队列中其诊断准确率为 93%(受试者工作特征曲线下面积:0.92),阳性预测值为 100%;针对肝纤维化定量检测的QuantiMeter,是惟一能通过无创方法直接量化肝纤维化程度的手段,对于随访肝硬化及其临床相关事件可能特别有用。除HCV 感染外,FibroMeters对HBV或HIV同时感染患者诊断准确率高,尤其是对酒精性肝病或非酒精性脂肪肝患者,FibroMeters有较高的诊断准确率(对于显著纤维化,受试者工作特征曲线下面积分别为0.96和0.94)。

关键词：肝纤维化活组织检查血清学弹性显像技术

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Hemodynamic and antifibrotic effects of a selective liver nitric oxide donor V-PYRRO/NO in bile duct ligated rats

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World Journal of Gastroenterology 2006年第41期12卷 6639-6645页

作者： Frédéric Moal Nary Veal Eric Vuillemin Eric Barrière Jianhua Wang Lionel Fizanne Frédéric Oberti Olivier Douay Yves Gallois Dominique Bonnefont-Rousselot Marie Christine Rousselet Paul Calès Laboratoire hifih UPRES 3859 Université Angers France Laboratoire de Biochimie Université Angers France INSERM U481 Hopital Beaujon Clichy France Laboratoire de Biochimie Hopital de 1a Salpêtrière Paris France

AIM: To assess whether a liver specific nitric oxide (NO) donor (V-PYRRO/NO) would prevent the development of portal hypertension and liver fibrosis in rats with bile duct ligation (BDL). METHODS: Treatment (placebo or V-PYRRO/NO 0.53 μmol/kg per hour) was administered i.v. to rats 2 d before BDL (D-2) and maintained until the day of hemodynamic measurement (D26). Intra-hepatic NO level was estimated by measuring liver cGMP level. Effects of V-PYRRO/NO on liver fibrosis and lipid peroxidation were also assessed. RESULTS: Compared to placebo treatment, V-PYRRO/ NO improved splanchnic hemodynamics in BDL rats: portal pressure was significantly reduced by 27% (P < 0.0001) and collateral circulation development was almost completely blocked (splenorenal shunt blood flow by 74%, P = 0.007). Moreover, V-PYRRO/NO significantly prevented liver fibrosis development in BDL rats (by 30% in hepatic hydroxyproline content and 31% in the area of fibrosis, P < 0.0001 respectively), this effect being probably due to a decrease in lipid peroxidation by 44% in the hepatic malondialdehyde level (P = 0.007). Interestingly, we observed a significant and expected increase in liver cGMP, without any systemic hemodynamic effects (mean arterial pressure, vascular systemic resistance and cardiac output) in both sham- operated and BDL rats treated with V-PYRRO/NO. This result is in accordance with studies on V-PYRRO/NO metabolism showing a specific release of NO in the *** in BDL rats improved liver fibrosis and splanchnic hemodynamics without any noxious systemic hemo- dynamic effects.

关键词： Nitric oxide Portal hypertension Liver fibrosis Hemodynamics Rats

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Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy

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World Journal of Gastroenterology 2007年第8期13卷 1195-1203页

作者： Pascal Veillon Christopher Payan Hélène Le Guillou-Guillemette Catherine Gaudy Franoise Lunel laboratory of Virology Angers University Hospital 4 rue Larrey 49933 Angers cedex 9 France HIFIH Laboratory UPRES EA 3859 IFR 132 University of Angers rue de Haute Reculée 49045 Angers France Departement of Microbiology EA 3882 Brest University Hospital 2 avenue Foch 29609 Brest cedex France University Francois Rabelais INSERM ERI 19 Faculty of Medecine 10 Boulevard Tonnellé BP 3223 37032 Tours Cedex France

AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNA- dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear. METHODS: HCV quasispecies were studied by clon- ing and sequencing of sequential isolates from patients infected by HCV genotype 1b. Patients were treated by IFN-α2b for 3 mo followed by IFN-α2b alone or com- bined IFN-R therapy for 9 additional months. Patients were categorized intro two groups based on their re- sponse to the treatments: 7 with sustained virological re- sponse (SVR) (quasispecies = 150) and 3 non-respond- ers (NR) to IFN-R (quasispecies = 106). RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispe- cies during therapy. Analysis of amino acids substitu- tions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate thetwo groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients. CONCLUSION: These results suggest that detailed mo- lecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection.

关键词： Hepatitis C virus Quasispecies NS5A region Interferon sensitivity-determining region V3 domain

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Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis:an international registry study

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Chinese Medical Journal 2023年第3期136卷 341-350页

作者： Huai Zhang Rafael S.Rios Jerome Boursier Rodolphe Anty Wah-Kheong Chan Jacob George Yusuf Yilmaz Vincent Wai-Sun Wong Jiangao Fan Jean-Francois Dufour George Papatheodoridis Li Chen Jorn M.Schattenberg Junping Shi Liang Xu Grace Lai-Hung Wong Naomi F.Lange Margarita Papatheodoridi Yuqiang Mi Yujie Zhou Christopher D.Byrne Giovanni Targher Gong Feng Minghua Zheng Department of Biostatistics and Medical Record The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325000China Department of Hepatology MAFLD Research CenterThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325000China Service d’Hépato-Gastroentérologie et Oncologie Digestive Centre Hospitalier Universitaire d’AngersAngersFrance Laboratoire hifih UPRES EA3859SFR ICAT 4208Universitéd’AngersAngersFrance Université Cote d’Azur CHUINSERMU1065C3M06204 NiceFrance Gastroenterology and Hepatology Unit Department of MedicineFaculty of MedicineUniversity of MalayaKuala LumpurMalaysia Storr Liver Centre Westmead Institute for Medical ResearchWestmead Hospital and University of SydneySydneyNSWAustralia Department of Gastroenterology School of MedicineMarmara UniversityIstanbulTurkey Department of Gastroenterology School of MedicineRecep Tayyip Erdogan UniversityRizeTurkey Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong 999077China Department of Gastroenterology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200000China University Clinic for Visceral Surgery and Medicine InselspitalUniversity Hospital BernBernSwitzerland Graduate School for Health Sciences University of BernBernSwitzerland Academic Department of Gastroenterology Medical School of National and Kapodistrian University of AthensGeneral Hospitalof Athens“Laiko”AthensGreece Department of Gastroenterology Ruijin HospitalShanghai 200000China Metabolic Liver Research Program I Department of MedicineUniversity Medical Center MainzMainzGermany The Affiliated Hospital of Hangzhou Normal University HangzhouZhejiang 310000China Tianjin Second People’s Hospital Tianjin 300000China Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghai 200000Ch

Background:Liver biopsy for the diagnosis of non-alcoholic steatohepatitis(NASH)is limited by its inherent invasiveness and possible sampling *** studies have shown that cytokeratin-18(CK-18)concentrations may be useful in diagnosing NASH,but results across studies have been *** aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of ***:Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease(NAFLD),and in all patients,circulating CK-18 M30 levels were *** with a NAFLD activity score(NAS)≥5 with a score of≥1 for each of steatosis,ballooning,and lobular inflammation were diagnosed as having definite NASH;individuals with a NAS≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver(NAFL).Results:A total of 2571 participants were screened,and 1008(153 with NAFL and 855 with NASH)were finally *** CK-18 M30 levels were higher in patients with NASH than in those with NAFL(mean difference 177 U/L;standardized mean difference[SMD]:0.87[0.69–1.04]).There was an interaction between CK-18 M30 levels and serum alanine aminotransferase,body mass index(BMI),and hypertension(P<0.001,P=0.026 and P=0.049,respectively).CK-18 M30 levels were positively associated with histological NAS in most *** area under the receiver operating characteristics(AUROC)for NASH was 0.750(95%confidence intervals:0.714–0.787),and CK-18 M30 at Youden’s index maximum was 275.7 U/*** sensitivity(55%[52%–59%])and positive predictive value(59%)were not ***:This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.

关键词： Apoptosis Diagnosis Cytokeratin-18 Liver histology Non-alcoholic steatohepatitis Non-alcoholic fatty liver disease

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An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease

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Hepatobiliary Surgery and Nutrition 2023年第3期12卷 386-403,I0014-I0016页

作者： Dan-Qin Sun Giovanni Targher Christopher D.Byrne David C.Wheeler Vincent Wai-Sun Wong Jian-Gao Fan Herbert Tilg Wei-Jie Yuan Christoph Wanner Xin Gao Michelle T.Long Mehmet Kanbay Mindie H.Nguyen Sankar D.Navaneethan Yusuf Yilmaz Yuli Huang Rino A.Gani Pierluigi Marzuillo Jérôme Boursier Huijie Zhang Chan-Young Jung Jin Chai Luca Valenti George Papatheodoridis Giovanni Musso Yu-Jun Wong Mohamed El-Kassas Nahum Méndez-Sánchez Silvia Sookoian Michael Pavlides Ajay Duseja Adriaan G.Holleboom Junping Shi Wah-Kheong Chan Yasser Fouad Junwei Yang Sombat Treeprasertsuk Helena Cortez-Pinto Masahide Hamaguchi Manuel Romero-Gomez Mamun Al Mahtab Ponsiano Ocama Atsushi Nakajima Chunsun Dai Mohammed Eslam Lai Wei Jacob George Ming-Hua Zheng Department of Nephrology Jiangnan University Medical CenterWuxiChina Affiliated Wuxi Clinical College of Nantong University WuxiChina Section of Endocrinology Diabetes and MetabolismDepartment of MedicineAzienda Ospedaliera Universitaria Integrata VeronaVeronaItaly Southampton National Institute for Health and Care Research Biomedical Research Centre University Hospital Southamptonand Southampton General HospitalUniversity of SouthamptonSouthamptonUK Department of Renal Medicine University College LondonLondonUK Department of Medicine and Therapeutics Chinese University of Hong KongHong KongChina Center for Fatty Liver Department of GastroenterologyXin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Internal Medicine I GastroenterologyEndocrinology&MetabolismMedical University InnsbruckInnsbruckAustria Department of Nephrology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Division of Nephrology Department of MedicineWürzburg University ClinicWürzburgGermany Department of Endocrinology and Metabolism Zhongshan HospitalFudan UniversityShanghaiChina Section of Gastroenterology Boston Medical CenterBoston University School of MedicineBostonMAUSA Division of Nephrology Department of Medicine(M.K.)Koc University School of MedicineIstanbulTurkey Division of Gastroenterology and Hepatology Department of MedicineStanford University Medical CenterPalo AltoCAUSA Department of Epidemiology and Population Health Stanford University Medical CenterPalo AltoCAUSA Section of Nephrology and Institute of Clinical and Translational Research Baylor College of Medicineand Michael E.DeBakey VA Medical CenterHoustonTXUSA Department of Gastroenterology School of MedicineMarmara UniversityIstanbulTurkey Department of Gastroenterology School of MedicineRecep Tayyip Erdoğan UniversityRizeTurkey Department of Cardiology Shunde HospitalSouthern Medical UniversityFoshanChina Division of Hepat

Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly *** 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without ***,to date,there is no appropriate guidance on CKD in individuals with ***,there has been little attention paid to the link between MAFLD and CKD in the Nephrology *** and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and ***:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.

关键词： Metabolic dysfunction-associated fatty liver disease(MAFLD) non-alcoholic fatty liver disease(NAFLD) chronic kidney disease(CKD) consensus

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