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Hepatitis c virus infection:are there still specific problems with genotype 3?

World Journal of Gastroenterology 2015年第42期21卷 12101-12113页

作者： claire Gondeau Georges Philippe Pageaux Dominique Larrey Department of Hepato-gastroenterology A Hospital Saint Eloi INSERM U1183 Institute of Regenerative Medicine and Biotherapy University of Montpellier

Hepatitis c virus(HcV) infection is one of the most common causes of chronic liver disease and the main indication for liver transplantation worldwide. As promising specific treatments have been introduced for genotype 1, clinicians and researchers are now focusing on patients infected by non-genotype 1 HcV, particularly genotype 3. Indeed, in the golden era of direct-acting antiviral drugs, genotype 3 infections are no longer considered as easy to treat and are associated with higher risk of developing severe liver injuries, such as cirrhosis and hepatocellular carcinoma. Moreover, HcV genotype 3 accounts for 40% of all HcV infections in Asia and is the most frequent genotype among HcV-positive injecting drug users in several countries. Here, we review recent data on HcV genotype 3 infection/treatment, including clinical aspects and the underlying genotype-specific molecular mechanisms.

关键词： Hepatitis c Genotype 3 Direct-acting antivirals In

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Hepatitis c virus recurrence after liver transplantation:A 10-year evaluation

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World Journal of Gastroenterology 2015年第13期21卷 3912-3920页

作者： Stefano Gitto Luca Saverio Belli Ranka Vukotic Stefania Lorenzini Aldo Airoldi Arrigo Francesco Giuseppe cicero Marcello Vangeli Lucia Brodosi Arianna Martello Panno Roberto Di Donato Matteo cescon Gian Luca Grazi Luciano De carlis Antonio Daniele Pinna Mauro Bernardi Pietro Andreone Department of Medical and Surgical Sciences University of Bologna and Azienda Ospedaliero-Universitaria di BolognaPoliclinico Sant’Orsola Malpighi40138 BolognaItaly Department of Gastroenterology Azienda Ospedaliero-Universitaria and University of Modena and Reggio Emilia41124 ModenaItaly Department of Hepatology and Gastroenterology Niguarda Hospital20162 MilanItaly Hepatobiliopancreatic and General Surgery Unit Regina Elena Institute00186 RomeItaly Department of General Surgery and Transplantation Niguarda Hospital20162 MilanItaly

AIM: To evaluate the predictors of 10-year survival of patients with hepatitis c recurrence. METHODS: Data from 358 patients transplanted between 1989 and 2010 in two Italian transplant centers and with evidence of hepatitis c recurrence were analyzed. A χ2, Fisher's exact test and Kruskal Wallis' test were used for categorical and continuous variables, respectively. Survival analysis was performed at 10 years after transplant using the Kaplan-Meier method, and a log-rank test was used to compare groups. A P level less than 0.05 was considered significant for all tests. Multivariate analysis of the predictive role of different variables on 10-year survival was performed by a stepwise cox logistic ***: The ten-year survival of the entire population was 61.2%. Five groups of patients were identified according to the virological response or lack of a response to antiviral treatment and, among those who were not treated, according to the clinical status(mild hepatitis c recurrence, "too sick to be treated" and patients with comorbidities contraindicating the treatment). While the 10-year survival of treated and untreated patients was not different(59.1% vs 64.7%, P = 0.192), patients with a sustained virological response had a higher 10-year survival rate than both the "non-responders"(84.7% vs 39.8%, P < 0.0001) and too sick to be treated(84.7% vs 0%, P < 0.0001). Sustained virological responders had a survival rate comparable to patients untreated with mild recurrence(84.7% vs 89.3%). A sustained virological response and young donor age were independent predictors of 10-year survival. cONcLUSION: Sustained virological response significantly increased long-term survival. Awaiting the interferon-free regimen global availability, antiviral treatment might be questionable in selected subjects with mild hepatitis c recurrence.

关键词： Hepatitis c Liver transplantation Hepatitis c viru

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Type-Driven Verification of Non-functional Properties 19

Type-Driven Verification of Non-functional Properties

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21st International Symposium on Principles and Practice of Declarative Programming (PPDP)

作者： Brown, christopher Barwell, Adam D. Marquer, Yoann Minh, celine Zendra, Olivier Univ St Andrews St Andrews Fife Scotland Univ Rennes CNRS INRIA IRISA Rennes France

ISBN: (纸本)9781450372497

Energy, Time and Security (ETS) properties of programs are becoming increasingly prioritised by developers, especially where applications are running on ETS sensitive systems, such as embedded devices or the Internet of Things. Moreover, developers currently lack tools and language properties to allow them to reason about ETS. In this paper, we introduce a new contract specification framework, called Drive, which allows a developer to reason about ETS or other non-functional properties of their programs as first-class properties of the language. Furthermore, we introduce a contract specification language, allowing developers to reason about these first-class ETS properties by expressing contracts that are proved correct by an underlying formal type system. Finally, we show our contract framework over a number of representable examples, demonstrating provable worst-case ETS properties.

关键词： IDRIS c time energy security non-functional properties proofs verification contracts

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Interferon-λ3 polymorphisms in pegylated-interferon-α plus ribavirin therapy for genotype-2 chronic hepatitis c

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World Journal of Gastroenterology 2015年第13期21卷 3904-3911页

作者： Haruya Ishiguro Hiroshi Abe Nobuyoshi Seki Tomonori Sugita Yuta Aida Munenori Itagaki Satoshi Sutoh Noritomo Shimada Tomomi Furihata Akihito Tsubota Yoshio Aizawa Division of Gastroenterology and Hepatology Department of Internal MedicineJikei University School of Medicine Katsushika Medical CenterTokyo 125-8506Japan Department of Gastroenterology and Hepatology Shinmatsudo Central General HospitalChiba 270-0034Japan Laboratory of Pharmacology and Toxicology Graduate School of Pharmaceutical SciencesChiba UniversityChiba 260-8675Japan Core Research Facilities for Basic Science Research Center for Medical ScienceJikei University School of MedicineTokyo 105-8461Japan

AIM: To evaluate interferon-λ3(IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin(Peg-IFNα/RBV) therapy for genotype 2(G2) chronic hepatitis ***: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis c virus(HcV) were treated with responseguided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response(RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype(TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HcV subgenotype 2a or ***: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response(SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate(96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5%(P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups(80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR(OR = 5.39, 95%cI: 1.29-22.62; P = 0.0189). In analysis according to HcV sub-genotype, no significant difference in the SVR rate was found between HcV sub-genotypes 2a and ***: In response-guided Peg-IFNα/RBV combination therapy for chronically HcV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.

关键词： Hepatitis c virus genotype 2 Interferon-λ3 single

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Boceprevir early-access for advanced-fibrosis/cirrhosis in Asia-pacific hepatitis c virus genotype 1 non-responders/relapsers

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World Journal of Gastroenterology 2015年第28期21卷 8660-8669页

作者： Wattana Sukeepaisarnjaroen Tri Pham Tewesak Tanwandee Saroja Nazareth Sam Galhenage Lindsay Mollison Leanne Totten Alan Wigg Rosalie Altus Anton colman Brenda Morales Sue Mason Tracey Jones Nadine Leembruggen Vince Fragomelli cheryl Sendall Richard Guan Dede Sutedja Soek Siam Tan Yock Young Dan Yin Mei Lee Widjaja Luman Eng Kiong Teo Yin Min Than Teerha Piratvisuth Seng Gee Lim Srinagarind Hospital Cabramatta Practice Siriraj Hospital Bangkok Royal Perth Hospital Fremantle Hospital Flinders Medical Centre Royal Adelaide Hospital Austin Hospital Royal Prince Alfred Hospital John Hunter Hospital Nepean Hospital Cairns Base Hospital Mount Elizabeth Medical Centre Gleneagles Hospital Selayang Hospital National University Health System Yong Loo Lin School of Medicine National University of Singapore Changi General Hospital NKC Institute of Gastroenterology and Hepatology Prince of Songkla University

AIM:To examined the efficacy and safety of treatment with boceprevir,PEGylated-interferon and ribavirin(PR)in hepatitis c virus genotype 1(HcVGT1) PR treatmentfailures in ***:The Boceprevir Named-Patient Program provided boceprevir to HcVGT1 PR *** physicians were invited to contribute data from their patients:baseline characteristics,ontreatment responses,sustained virological response at week 12(SVR12),and safety were collected and *** analysis was performed to determine predictors of ***:150 patients were enrolled from Australia,Malaysia,Singapore and Thailand(Asians = 86,caucasians = 63).Overall SVR12 was 61%(Asians= 59.3%,caucasians = 63.5%).SVR12 was higher in relapsers(78%) compared with non-responders(34%).On-treatment responses predicted SVR,with undetectable HcVRNA at week 4,8 and 12 leading to SVR12 s of 100%,87%,and 82%respectively,and detectable HcVRNA at week 4,8 and 12,leading to SVR12 s of 58%,22%and 6%*** patients were similar to caucasian patients with regards to on-treatment *** with cirrhosis(n= 69) also behaved in the same manner with regards to on-treatment *** with the IL28 B cc genotype(80%) had higher SVRs than those with the cT/TT(56%) genotype(P = 0.010).Multivariate analysis showed that TW8 and TW12 responses were independent predictors of *** adverse events occurred in 18.6%:sepsis(2%),decompensation(2.7%) and blood transfusion(14%).Discontinuations occurred in 30.7%,with 18.6%fulfilling stopping ***:Boceprevir can be used successfully in PR treatment failures with a SVR12 > 80%if they have good on-treatment responses;however,discontinuations occurred in 30%because of virological failure or adverse events.

关键词： chronic hepatitis c Treatment failure Rapid virological response Lead-in Null response Partial response Relapse cirrhosis Response guidedtherapy

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Hepatitis c virus and antiviral innate immunity:Who wins at tug-of-war?

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World Journal of Gastroenterology 2015年第13期21卷 3786-3800页

作者： Da-Rong Yang Hai-Zhen Zhu Department of Molecular Medicine of College of Biology State Key Laboratory of Chemo/Biosensing and ChemometricsHunan University Research Center of Cancer Prevention and Treatment Translational Medicine Research Center of Liver CancerHunan Provincial Tumor Hospital (Affiliated Tumor Hospital of Xiangya Medical School of Central South University)

Hepatitis c virus(HcV) is a major human pathogen of chronic hepatitis and related liver diseases. Innate immunity is the first line of defense against invading foreign pathogens, and its activation is dependent on the recognition of these pathogens by several key sensors. The interferon(IFN) system plays an essential role in the restriction of HcV infection via the induction of hundreds of IFN-stimulated genes(ISGs) that inhibit viral replication and spread. However, numerous factors that trigger immune dysregulation, including viral factors and host genetic factors, can help HcV to escape host immune response, facilitating viral persistence. In this review, we aim to summarize recent advances in understanding the innate immune response to HcV infection and the mechanisms of ISGs to suppress viral survival, as well as the immune evasion strategies for chronic HcV infection.

关键词： Hepatitis c virus Interferon Interferonstimulated

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Prevalence and knowledge of hepatitis c in a middle-aged population,Dunedin,New Zealand

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World Journal of Gastroenterology 2015年第35期21卷 10224-10233页

作者： Jane Vermunt Margaret Fraser Peter Herbison Anna Wiles Martin Schlup Michael Schultz Department of Medicine Dunedin School of MedicineUniversity of Otago Gastro-enterology Unit Dunedin HospitalSouthern District Health Board Department of Preventive and Social Medicine University of Otago

AIM:To determine the prevalence of infection with hepatitis c virus(HcV) in those most at risk of advanced liver disease and to identify gaps in knowledge of ***: Questionnaires were mailed to randomly selected residents aged 40-59 to assess the extent of their general knowledge about HcV. The questionnaire assessed demographics, the extent of general knowledge about viral hepatitis, potential risks for infection and the prevalence of risk factors associated with increased progression of liver fibrosis. Anonymised residual laboratory blood samples from 40-59 years old people from Dunedin taken in hospital or in the community, were tested for HcV antibodies and alanine transaminase(ALT), aspartate transaminase(AST), gamma-glutamyl transpeptidase(GGT). Linear regression was performed to examine whether the demographics sex, age, socio-economic status, qualification level and occupation sector(categorical variables) were predictors of level of general knowledge about hepatitis. For the demographics that werefound to be significant predictors of score outcome, multiple regression analysis was used to determine independent effects. χ2 tests were used to compare our selected sample and our responder population demographics, to the demographics of the entire 40-59 years old population in Dunedin using the 2006 NZ census data. Exact confidence intervals for the proportion positive for HcV and HBV were calculated using the binomial ***: The response rate to the mailed questionnaire was 431/1400(30.8%). On average 59.4% questions were answered correctly. Predictors for higher scores, indicating greater knowledge about symptoms and transmission included sex(female, P < 0.01), higher level of qualification(P < 0.000) and occupation sector(P < 0.000). Sharing intravenous drug utensils was a known risk factor for disease transmission(94.4%), but the sharing of common household items such as a toothbrush was not. 93% of the population were unaware that HcV

关键词： Hepatitis c Prevalence Knowledge Treatment Transmi

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Analysis and Performance Evaluation of Novel Microstrip Patch Antenna Based on Two Parasitic Ring Resonators and Partial Ground Plane for Multiband Applications

Analysis and Performance Evaluation of Novel Microstrip Patc...

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International Electromagnetics and Antenna conference (IEMANTENNA)

作者： Boutejdar, Ahmed Halim, Bishoy I. German Res Fdn DFG Dept Microwave Engn Bonn Germany Alexandria Univ Commun & Elect Dept Alexandria Egypt

ISBN: (纸本)9781728153353

In this paper, a novel planar monopole antenna for multi-band applications is proposed. The simulated results show that the proposed antenna operates at multiband resonance frequencies, which covers different wireless communication applications. The proposed antenna consists of a quasi-modified rectangular radiating patch with a partial ground plane and two parasitic elements (open-loop-ring resonators) to serve as coupling-bridges. A stepped cut at the partial ground plane is used, to achieve the multi-band features. The proposed antenna is simulated and optimized using High-Frequency Simulation System (HFSS). The antenna topology possesses an area of 30x30 x1.27 mm(3). The measured results demonstrate that the proposed antenna has impedance bandwidths for -10 dB return loss which meet the requirements of worldwide interoperability for microwave access (Wi-MAX), c- (Uplink), X (Uplink) and Ku- (Uplink) band applications. An Acceptable agreement is obtained between measurement and simulation results. Experimental results show that the antenna is successfully simulated and measured.

关键词： Planar monopole antenna Partial ground plane HFSS Wi-MAX c X& Ku

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Progress in the development of vaccines for hepatitis c virus infection

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World Journal of Gastroenterology 2015年第42期21卷 11984-12002页

作者： Faezeh Ghasemi Sina Rostami Zahra Meshkat Department of New Sciences and Technology Faculty of Medicine Mashhad University of Medical Sciences Department of Biology Faculty of Sciences Ferdowsi University of Mashhad The Influenza Centre Department of Clinical Science University of Bergen Antimicrobial Resistance Research Center Faculty of Medicine Mashhad University of Medical Sciences

The hepatitis c virus(HcV), first described in 1989, is now a leading cause of liver cirrhosis and hepatocellular carcinoma. With more than 170 million people infected globally, this virus is a major public health issue. The current standard therapy is based on interferon in combination with ribavirin. This costly therapy often fails to completely clear the infection and is associated with adverse side effects. Recent anti-HcV therapies are interferon-free direct-acting antiviral(DAA) regimens for HcV, including simeprevir, sofosbuvir, and ledipasvir, which have effects on non-structural proteins. DAA regimens have several advantages, such as specifically targeting HcV viral replication, accompanied by very high sustained virological response rates and lower side effects like flu-like syndrome. These facts plus the fact that most HcV cases progress to chronic infection suggest the potential need for an efficient HcV vaccine. Different innovative methods, including methods based on peptide, recombinant protein, DNA, vector-based, and virus-like particles, have been introduced for the development of HcV vaccines. An extensive number of studies have been published on these vaccines, and some vaccines were even tested in clinical trials. In the current review, progress in the development of preventive and therapeutic vaccines against the HcV is reviewed in the context of peptide vaccines, recombinant protein vaccines, HcV-like particle, DNA vaccines and viral vectors expressing HcV genes.

关键词： Preventive vaccine Therapeutic vaccine Hepatitis c

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Hepatitis c virus NS5A promotes insulin resistance through IRS-1 serine phosphorylation and increased gluconeogenesis

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World Journal of Gastroenterology 2015年第43期21卷 12361-12369页

作者： Fahed Parvaiz Sobia Manzoor Jawed Iqbal Mehuli Sarkar-Dutta Muhammad Imran Gulam Waris Atta-urRahman School of Applied Biosciences National University of Sciences and Technology Department of Microbiology and Immunology Rosalind Franklin University of Medicine and Science

AIM: To investigate the mechanisms of insulin resistance in human hepatoma cells expressing hepatitis c virus(HcV) nonstructural protein 5A(NS5A).METHODS: The human hepatoma cell lines,Huh7 and Huh7.5,were infected with HcV or transientlytransfected with a vector expressing HcV NS5 A. The effect of HcV NS5 A on the status of the critical players involved in insulin signaling was analyzed using realtime quantitative polymerase chain reaction and Western blot assays. Data were analyzed using Graph Pad Prism version ***: To investigate the effect of insulin treatment on the players involved in insulin signaling pathway,we analyzed the status of insulin receptor substrate-1(IRS-1) phosphorylation in HcV infected cells or Huh7.5 cells transfected with an HcV NS5 A expression vector. Our results indicated that there was an increased phosphorylation of IRS-1(Ser307) in HcV infected or NS5 A transfected Huh7.5 cells compared to their respective controls. Furthermore,an increased phosphorylation of Akt(Ser473) was observed in HcV infected and NS5 A transfected cells compared to their mock infected cells. In contrast,we observed decreased phosphorylation of Akt Thr308 phosphorylation in HcV NS5 A transfected cells. These results suggest that Huh7.5 cells either infected with HcV or ectopically expressing HcV NS5 A alone have the potential to induce insulin resistance by the phosphorylation of IRS-1 at serine residue(Ser307) followed by decreased phosphorylation of Akt Thr308,Fox01 Ser256 and GSK3β Ser9,the downstream players of the insulin signalingpathway. Furthermore,increased expression of PEcK and glucose-6-phosphatase,the molecules involved in gluconeogenesis,in HcV NS5 A transfected cells was ***: Taken together,our results suggest the role of HcV NS5 A in the induction of insulin resistance by modulating various cellular targets involved in the insulin signaling pathway.

关键词： Hepatitis c virus nonstructural protein 5A Insulin

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