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Prevalence of IFNL3 rs4803217 single nucleotide polymorphism and clinical course of chronic hepatitis c

World Journal of Gastroenterology 2017年第21期23卷 3815-3824页

作者： Bogna Swiatek-Koscielna Ewelina Kaluzna Ewa Strauss Jerzy Nowak Iwona Bereszyńska Ewelina Gowin Jacek Wysocki Jolanta Rembowska Dominika Barcińska Iwona Mozer-Lisewska Danuta Januszkiewicz-Lewandowska Institute of Human Genetics Polish Academy of Sciences Department of General and Vascular Surgery Poznan University of Medical Sciences Department of Infectious Diseases Poznan University of Medical Sciences Department of Family Medicine Poznan University of Medical Sciences Department of Preventive Medicine Poznan University of Medical Sciences Department of Medical Diagnostics Department of Pediatric Oncology Hematology and Bone Marrow TransplantationPoznan University of Medical Sciences

AIM To evaluate the association of IFNL3(IL28B) SNP rs4803217 with severity of disease and treatment outcome in chronic hepatitis c(cHc).METHODS The study enrolled 196 cHc Polish patients(82 women and 114 men in age 20-64) infected with hepatitis c virus(HcV) genotype 1. They were treatment na?ve and qualified to pegylated interferon alpha(PEG-IFN-α) and ribavirin(RBV) therapy. The analyzed baseline parameters included: degree of inflammation, stage of fibrosis, viral load as well as alanine aminotransferase(ALT), asparagine aminotransferase(AST) and total bilirubin(TBIL). The analysis of response to therapy included: sustained virological response(SVR), defined as undetectable serum HcV RNA level six month after completion of 48-wk therapy, and relapse, defined as achieving undetectable viral load at the end of treatment but not SVR. HcV genotyping and HcV RNA quantification were performed using commercially available tests. DNA was isolated from peripheral blood mononuclear cells or from buccal cell swabs. In addition to rs4803217, also single nucleotide polymorphisms(SNPs)(rs12979860, rs8099917 and rs12980275) of known significance in predicting of HcV clearance were analyzed. SNPs were determined by high resolution melt analysis and confirmed by sequencing of amplicons. RESULTS Frequency of rs4803217 genotypes in studied group was as follows: 27.55%; 54.59% and 17.86% for cc, cA and AA, respectively. The rs4803217 SNP, similar to other analyzed SNPs, was not associated with severity of cHc(grade of inflammation, stage of fibrosis, baseline viral load as well as biochemical parameters: ALT, AST, TBIL). It was demonstrated that the rs4803217 c allele is associated with SVR(c vs A: P c allele: P = 0.0002) and nonrelapse(c vs A: P = 0.001; dose of c allele: P = 0.002). Moreover, it was found that patients with cc genotype have significantly higher response rates as compared with cA/AA patients(P carrying A allele are sig

关键词： hepatitis c virus chronic hepatitis c Interferon lambda 3 Interleukin 28B rs4803217

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Alkaline phosphatase predicts relapse in chronic hepatitis c patients with end-of-treatment response

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World Journal of Gastroenterology 2010年第19期16卷 2407-2410页

作者： Gerd Bodlaj Rainer Hubmann Karim Saleh Tatjana Stojakovic Georg Biesenbach Jrg Berg Second Department of Medicine General Hospital Linz A-4020 Linz Austria clinical Institute of Medical and chemical Laboratory Diagnostics Medical University of Graz A-8010 Graz Austria Institute of Laboratory Medicine General Hospital Linz A-4020 Linz Austria

AIM: To investigate relapse predictors in chronic hepatitis c (cHc) patients with end-of-treatment response (ETR), after pegylated interferon-α (PegIFN-α) and ribavirin treatment. METHODS: In a retrospective study we evaluated a spectrum of predictors of relapse after PegIFN-α and ribavirin treatment in 86 cHc patients with ETR. Viral loads were determined with real-time reverse transcrip-tion polymerase chain reaction. hepatitis c virus geno-typing was performed by sequencing analysis. Patients with genotype 1 were treated for 48 wk with 180 μg PegIFN-α2a or 1.5 μg/kg PegIFN-α2b once weekly plus ribavirin at a dosage of 1000 mg/d for those under 75 kg or 1200 mg/d for those over 75 kg. Patients with geno- types 2 and 3 were treated for 24 wk with 180 μgPegIFN-α2a or 1.5 μg/kg PegIFN-α2b once weekly plus ribavirin at a dosage of 800 mg/d. RESULTS: In all ETR patients, binary logistic regression analysis identif ied absence of complete early virological response (cEVR) (OR 27.07, 95% cI: 3.09-237.26, P cI: 2.1-18.03, P 26 kg/m2 (OR: 8.27, 95% cI: 2.22-30.84, P ctors of relapse. When cEVR patients were analyzed exclusively, ALP prior to therapy ctor of relapse. cONcLUSION: Lower levels of ALP prior to, during and after therapy seem to be associated with a higher risk of relapse in cHc patients with ETR.

关键词： Alkaline phosphatase chronic hepatitis c Pegylated interferon Predictor Relapse

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Insulin resistance,adipokine profile and hepatic expression of SOcS-3 gene in chronic hepatitis c

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World Journal of Gastroenterology 2014年第30期20卷 10449-10456页

作者： Kamila Wójcik Elzbieta Jabonowska Aleksandra Omulecka Anna Piekarska Department of Infectious Diseases and Hepatology Medical University of Lodz91-347 VódzPoland Department of Pathology Bieganski Hospital of Lodz91-347 VódzPoland

AIM: To analyze adipokine concentrations, insulin resistance and hepatic expression of suppressor of cytokine signaling 3 (SOcS-3) in patients with chronic hepatitis c genotype 1 with normal body weight, glucose and l... 详细信息

关键词： Adipokines Steatosis chronic hepatitis c Insulin resistance SOcS-3 gene

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Immunogenicity of recombinant hepatitis B vaccine in treatment-nave and treatment-experienced chronic hepatitis c patients: The effect of pegylated interferon plus ribavirin treatment

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World Journal of Gastroenterology 2006年第27期12卷 4420-4424页

作者： Ioannis S Elefsiniotis Elena Vezali Konstantinos Kamposioras Konstantinos D Pantazis Radostina Tontorova Ioannis Ketikoglou Antonios Moulakakis George Saroglou Department of Internal Medicine Hepatology UnitHippokration Hospital of AthensAthensGreeceDepartment of Internal MedicineFaculty of NursingUniversity of AthensAthensGreece Department of Internal Medicine Hepatology UnitHippokration Hospital of AthensAthensGreece Department of Internal Medicine Faculty of NursingUniversity of AthensAthensGreece

AIM： To retrospectively evaluate the vaccinationinduced anti-HBs seroconversion rates in treatmentnaive and treatment-experienced chronic hepatitis c （cHc） patients. Also to prospectively evaluate the seroconversion rates in cHc patients during pegylated interferon （PEG） plus ribavirin （RIB） treatment. METHODS： Seventy treatment-naive cHc patients （group A）, 22 sustained virological responders-SVR following interferon （IFN） plus RIB treatment cHc patients （group B） and 121 healthy subjects （group c） had been participated in the same HBV vaccination schedule （20 μg, 0-1-6 mo）. Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine. Moreover, we prospectively selected 30 non-cirrhotic cHc patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups： Group-1, 15 cHc patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment. Determination of anti-HBs was performed at mo 1, 2, and 7. Statistical analysis of data was based on ANOVA student＇s t-test and chi-square analysis （P 〈 0.05）. RESULTS： Fifty-eight of 70 group A patients （82.85%）, 20/22 group B （90.9%） and 112/121 healthy subjects （92.56%） had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive cHc patients （P = 0.04）. The corresponding rates were comparable between group A and group B cHc patients （P = 0.38）. The vast majority of non-responders （10/14, 71.43%） had been infected by genotype-1 of HcV. The seroconversion rates were comparable between group 1 and 2 cHc patients at mo 1 （20% versus 26.7%, P = 0.67）, mo 2 （46.7% vs 60%, P = 0.46） and mo 7 （86.7% versus 93.3%, P = 0.54） of follow-up. cONcLUSION： The immunogenicity of HBV vaccine seems to be lower in cHc patients compared to healthy subjects

关键词： hepatitis B vaccine chronic hepatitis c Interferon Ribavirin

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Factors correlating with acoustic radiation force impulse elastography in chronic hepatitis c

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World Journal of Gastroenterology 2014年第5期20卷 1289-1297页

作者： Toru Nishikawa Senju Hashimoto Naoto Kawabe Masao Harata Yoshifumi Nitta Michihito Murao Takuji Nakano Yuko Mizuno Hiroaki Shimazaki Toshiki Kan Kazunori Nakaoka Yuka Takagawa Masashi Ohki Naohiro Ichino Keisuke Osakabe Kentaro Yoshioka Department of Liver Biliary Tract and Pancreas Diseases Fujita Health University Faculty of Medical Technology School of Health Sciences Fujita Health University

AIM: To investigate the factors other than fibrosis stage correlating with acoustic radiation force impulse (ARFI) elastograpy in chronic hepatitis c.

关键词： Acoustic radiation force impulse Body mass index chronic hepatitis c computer-assisted morphometric image analysis Fibrosis stage Hyaluronic acid Liver stiffness measurement Transient elastography Velocity of shear wave

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Risk factors for liver-related mortality in chronic hepatitis c patients:A deceased case-living control study

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World Journal of Gastroenterology 2014年第18期20卷 5519-5526页

作者： Qing-Lei Zeng Guo-Hua Feng Ji-Yuan Zhang Yan chen Bin Yang Hui-Huang Huang Xue-Xiu Zhang Zheng Zhang Fu-Sheng Wang The Institute of Translational Hepatology Beijing 302 HospitalPeking University Health Science Center Research center for Biological Therapy Beijing 302 Hospital center of Therapeutic Research for Hepatocellular carcinoma Beijing 302 Hospital Department of Interventional Radiology Beijing 302 Hospital Department of Intensive care Unit Beijing 302 Hospital

AIM: To investigate the risk factors for liver-related mortality in chronic hepatitis c (cHc) patients.

关键词： hepatitis c virus chronic hepatitis c Risk factor Mortality case control study

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Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis c

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World Journal of Gastroenterology 2016年第44期22卷 9744-9751页

作者： ángel Hernández-Bartolomé Rosario López-Rodríguez María Jesús Borque Leticia González-Moreno Yolanda Real-Martínez Luisa García-Buey Ricardo Moreno-Otero Paloma Sanz-cameno Gastroenterology Service Instituto Investigación Sanitaria Princesa Molecular Biology Unit Instituto Investigación Sanitaria Princesa cIBERehd

AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis c(cHc).METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays(ELISA) in samples from 179 cirrhotic and non-cirrhotic cHc patients, classified according to the METAVIR *** were compared by non-parametric MannWhitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics(AUc-ROc).RESULTS Peripheral blood concentrations of Ang1 and Ang2 in cHc patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic(P cantly increased as cHc progressed to the end stage of liver disease(P consequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis(P ce of each angiopoietin for the diagnosis of cirrhosis reached notable AUc-ROc values(above 0.7, both), but the Ang2/Ang1 ratio was much better(AUc-ROc = 0.810) and displayed outstanding values of sensitivity(71%), specificity(84%) and accuracy(82.1%) at the optimal cut-off(10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in *** Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target.

关键词： chronic hepatitis c Area under the curve of receiver operator characteristics Liver fibrosis cirrhosis Angiopoietin-2 Angiopoietin-1 Biomarker Angiogenesis

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Impact of hepatitis c virus core mutations on the response to interferon-based treatment in chronic hepatitis c

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World Journal of Gastroenterology 2016年第37期22卷 8406-8413页

作者： camelia Sultana Gabriela Oprisan Monica Delia Teleman Sorin Dinu HepGen 88/2012 Project Team cristiana Oprea Mihai Voiculescu Simona Ruta Virology Discipline Carol Davila University of Medicine and Pharmacy Emergent Diseases Department Stefan S.Nicolau Institute of Virology Faculty of Pharmacy Titu Maiorescu University Molecular Epidemiology Laboratory NIRDMI Cantacuzino Department of Microbiology and Epidemiology Carol Davila University of Medicine and Pharmacy Victor Babes clinic of Infectious and Tropical Diseases Fundeni Institute

AIM To determine whether hepatitis c virus(HcV) core substitutions play a role in the response to interferon-based treatment in caucasian patients. METHODS One hundred eight HcV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein(Big Dye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in host IL28 B gene rs12979860(custom TaqM an 5' allelic discrimination assay; Applied Biosystems).RESULTS Of the patients, all were infected with HcV genotype 1b, 44.4% had low baseline HcV viral load, and 37.9% had mild/moderate fibrosis. Only 38.9% achieved therapeutic success, defined as sustained virological response(SVR). Eighty-eight percent of the patients presented at least one substitution at core position 70(R70Q/H) or/and position 91(L91M). The favorable IL28 B cc polymorphism was detected in only 17.6% of the patients. In the univariate analysis, young age(P ce(P = 0.004), IL28 B cc genotype(P ce of core mutations(P = 0.005), achievement of rapid virologic response(P cal response(P cantly correlated with SVR. A multivariate analysis revealed three independent predictors of therapeutic success: young age(P ce of core substitutions(P = 0.04) and IL28 B cc genotype(P correctly classified 75.9% of SVR cases with a positive predictive value of 80.7%. cONcLUSION HcV core mutations can help distinguish between patients who can still benefit from the affordable IFNbased therapy from those who must be treated with DAAs to prevent the evolution towards end-stage liver disease.

关键词： chronic hepatitis c caucasian patients core substitutions IL28B polymorphism Treatment

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Successful interferon desensitization in a patient with chronic hepatitis c infection

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World Journal of Gastroenterology 2009年第33期15卷 4196-4198页

作者： Seyed Alireza Taghavi Ahad Eshraghian Gastroentero-hepatology Research center of Shiraz University of Medical Science Nemazee Hospital

Treatment of hepatitis c, even when absolutely necessary, is almost impossible when interferon cannot be administered for any reason. We report a 65-year-old patient with chronic hepatitis c virus (HcV) infection and fibrosis, who was unable to receive interferon because of systemic hypersensitivity. The patient was desensitized successfully through gradual incremental exposure to interferon, and HcV infection was eradicated after a complete course of treatment, with no further allergic reactions. This case report that describes successful eradication of hepatitis c in a patient with advanced liver disease after desensitization to interferon revealed that desensitization may not necessarily damage the therapeutic efficacy of the drug.

关键词： chronic hepatitis c Desensitization Drug hypersensitivity Interferon a2b Ribavirin

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current treatment options and response rates in children with chronic hepatitis c

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World Journal of Gastroenterology 2012年第2期18卷 99-104页

作者： Stefan Wirth Helios Medical centre Wuppertal Department of PediatricsWitten-Herdecke UniversityD-42283 WuppertalGermany

Vertical transmission has become the most common mode of transmission of hepatitis c virus (HcV) in *** rate of perinatal transmission from an HcVinfected mother to her child ranges from 2% to 5% and the prevalence of HcV in children in developed countries ranges between 0.1% and 0.4%.Spontaneous viral clearance seems to be dependent on the genotype and has been reported between 2.4%-25%.For chronically infected patients,treatment with recombinant polyethylene glycol (PEG)-interferon α-2b and daily ribavirin has now been approved as standard treatment for children 2-17 years of *** five large prospective studies,a total of 318 children and adolescents aged 3-17 years were treated either with subcutaneous PEG-interferon α-2b at a dose of 1-1.5 μg/kg or 60 μg/m2 once a week in combination with oral ribavirin (15 mg/kg per day) or PEG-interferon α-2a with *** with genotype 1 and 4 received the medication for 48 wk and individuals with genotype 2 and 3 mainly for 24 *** sustained viral response (SVR) was achieved in 193/318 (60.7%) of treated *** for genotype;120/234 (51%) with genotype 1,68/73 (93%) with genotype 2/3,and 6/11 (55%) with genotype 4 showed *** rate was between 7.7% and 17%.Overall,treatment was well tolerated;how-ever,notable side effects were present in approximately 20%.According to recent experiences in the treatment of chronic hepatitis c in children and adolescents,a combination of PEG-interferon α with ribavirin has been found to be well tolerated and highly efficacious,particularly in individuals with genotype 2/***,this treatment can be recommended as standard of care until more effective treatment options will become available for genotype 1 patients.

关键词： chronic hepatitis c Treatment children Polyethylene glycol-interferon and ribavirin Responserate

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