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Predictors of functional benefit of hepatitis c therapy in a‘real-life’cohort

World Journal of Gastroenterology 2018年第7期24卷 852-861页

作者： Niels Steinebrunner Kerstin Stein catharina Sandig Thomas Bruckner Wolfgang Stremmel Anita Pathil Department of Internal Medicine IV University Hospital HeidelbergHeidelberg 69120Germany Department of Gastroenterology Hepatology and Infectious DiseasesUniversity Hospital of MagdeburgMagdeburg 39120Germany Department of Medical Biometry Institute of Medical Biometry and Informatics(IMBI)Heidelberg 69120Germany

AIM To define predictors of functional benefit of direct-acting antivirals(DAAs) in patients with chronic hepatitis c virus(HcV) infection and liver *** We analysed a cohort of 199 patients with chronic HcV genotype 1, 2, 3 and 4 infection involving previously treated and untreated patients with compensated(76%) and decompensated(24%) liver cirrhosis at two tertiary centres in Germany. Patients were included withtreatment initiation between February 2014 and August 2016. All patients received a combination regimen of one or more DAAs for either 12 or 24 wk. Predictors of functional benefit were assessed in a univariable as well as multivariable model by binary logistic regression *** Viral clearance was achieved in 88%(175/199) of patients. Sustained virological response(SVR) 12 rates were as follows: among 156 patients with genotype 1 infection the SVR 12 rate was 90%(n = 141); among 7 patients with genotype 2 infection the SVR 12 rate was 57%(n = 4); among 30 patients with genotype 3 infection the SVR 12 rate was 87%(n = 26); and among 6 patients with genotype 4 infection the SVR 12 rate was 67%(n = 4). Follow-up MELD scores were available for 179 patients. A MELD score improvement was observed in 37%(65/179) of patients, no change of MELD score in 41%(74/179) of patients, and an aggravation was observed in 22%(40/179) of patients. We analysed predictors of functional benefit from antiviral therapy in our patients beyond viral eradication. We identified the child-Pugh score, the MELD score, the number of platelets and the levels of albumin and bilirubin as significant factors for functional *** Our data may contribute to the discussion of potential risks and benefits of antiviral therapy with individual patients infected with HcV and with advanced liver disease.

关键词： functional benefit direct acting antiviral hepatitis c cirrhosis real-life data

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Hepatitis c virus infection in children in the era of directacting antiviral

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World Journal of Gastroenterology 2018年第24期24卷 2555-2566页

作者： Malgorzata Pawlowska Malgorzata Sobolewska-Pilarczyk Krzysztof Domagalski Department of Paediatric Infectious Diseases and Hepatology Faculty of MedicineCollegium MedicumNicolaus Copernicus University centre For Modern Interdisciplinary Technologies Nicolaus Copernicus University

Hepatitis c virus(HcV) infection remains an important global health problem with chronic infection affecting approximately 11 million children worldwide. The emergence of direct-acting antiviral(DAA) therapies and the development of non-invasive methods for the determination of liver fibrosis will significantly improve the management of paediatric patients with chronic HcV infection in subsequent years. For paediatric patients, a new era of highly effective DAA agents is beginning, and the first results of available clinical trials are very promising. In this era, the identification and monitoring of patients continues to be an important issue. The availability of non-invasive serological and imaging methods to measure hepatic fibrosis enables the identification of patients with significant or advanced liver fibrosis stages. This article summarizes the current data on the epidemiology and progress of research aimed to evaluate the new therapies and non-invasive methods for liver injury in paediatric patients with chronic hepatitis c.

关键词： biomarkers of liver injury adolescents epidemiology direct-acting antiviral Hepatitis c virus non-invasive methods children

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Real life efficacy and safety of direct-acting antiviral therapy for treatment of patients infected with hepatitis c virus genotypes 1, 2and 3 in northwest china

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World Journal of Gastroenterology 2019年第44期25卷 6551-6560页

作者： Ying Yang Feng-Ping Wu Wen-Jun Wang Juan-Juan Shi Ya-Ping Li Xin Zhang Shuang-Suo Dang Department of Infectious Diseases the Second Affiliated Hospital of Xi’an Jiaotong University

BAcKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis c virus(HcV)genotypes 1,2 and *** real-world data is still not enough,especially in *** To investigate the efficacy and safety of DAA-based regimens in a real-life setting in *** This study included 366 patients infected with HcV genotypes 1,2 and 3,with or without cirrhosis,who were observed between May 2015 and December *** were treated with ledipasvir and sofosbuvir(SOF)(genotype 1)with or without ribavirin(RBV),SOF and RBV(genotype 2),or SOF and daclatasvir(genotype 3),with or without RBV,for 12 or more *** participants’sustained virological responses(SVR)at post-treatment week 12(SVR12)was the primary *** occurrence of adverse events and drug-drug interactions were *** In the 366 patients,genotype 1(59.0%)was the most common genotype,followed by genotypes 2(34.4%)and 3(6.6%).Liver cirrhosis was diagnosed in 154(42.1%)***(13.7%)patients were ***-to-treat analysis revealed that SVR12 was 86.3%(316/366).For modified intention-totreat analysis,SVR12 was achieved in 96.6%of overall patients(316/327),96.3%in patients with genotype 1,97.5%in those with genotype 2,and 95.0%in those with genotype *** of the treatment failures were due to lack of follow-up(3cases had non-responses,1 had virological breakthrough,11 relapsed and 36 did not participate in the follow-up).There was no significant difference in SVR between different genotypes and liver statuses(Pchieved an end of treatment response were more likely to achieve SVR12(PcV RNA levels or history of antiviral therapy(P>0.05 for all).The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%.Most of the

关键词： Hepatitis c virus Direct-acting antiviral agents Efficacy Safety Drug-drug interactions Real-life experience

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World Journal of Gastroenterology 2015年第13期21卷 4006-4013页

作者： Yuan-Yuan Zhang Hong-Bo chen Yin Xu Peng Huang Jie Wang Yun Zhang Rong-Bin Yu Jing Su Department of Epidemiology and Biostatistics School of Public HealthNanjing Medical University Department of Infectious Diseases Jurong Peoples’ Hospital Department of General Practice Kangda CollegeNanjing Medical University Institute of Epidemiology and Microbiology the Institute of Military Medicine of Nanjing Command

AIM: To determine the association between rapid viral response and IL28 B, IL28 RA, IL10 RB and Mx A polymorphisms in the chinese Han ***: The study cohort consisted of 238 chronic hepatitis c patients treated with interferon(IFN)-α-2b and ribavirin. Six single nucleotide polymorphisms were genotyped using the ABI Taq Man allelic discrimination assay. Biochemical indices were measured at baseline. Serum hepatitis c virus(HcV) RNA was detected at weeks 0, 4, 12 and 24 of ***: Only IL28 B rs12980275 was associated with treatment response in the chinese Han population. Patients carrying AG/GG genotypes had a reduced rapid viral response compared with patients carrying the AA genotype(additive model: adjusted OR = 0.43, 95%cI: 0.24-0.75). It took less time for patients with the AA genotype to achieve a viral load copies/m L(logrank test, P = 0.004). In addition, the protective effect of genotype AA was independent of baseline viral load. HcV genotype, and baseline white blood cell count, α-fetoprotein and viral load might also help predict treatment response. The area under the receiveroperating characteristic curve was 0.726. cONcLUSION: IL28 B rs12980275 AA genotype is a strong predictor of positive response to IFN therapy in chinese Han patients with hepatitis c.

关键词： Hepatitis c virus Interferon Rapid viral response

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Scotomas in molecular virology and epidemiology of hepatitis c virus

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World Journal of Gastroenterology 2013年第44期19卷 7910-7921页

作者： Yue Wang National Institute for Viral Disease control and Prevention China CDC collaborative Innovation center for Diagnosis and Treatment of Infectious Diseases Zhejiang University

In the 1970s,scientists learned of a new pathogen causing non-A,non-B *** approaches were used to isolate and characterize this new pathogen,but it could be transmitted experimentally only to chimpanzees and progress was slow until the pathogen was identified as hepatitis c virus(HcV)in *** then,research and treatment of HcV have expanded with the development of modern biological medicine:HcV genome organization and polyprotein processing were delineated in 1993;the first three-dimensional structure of HcV nonstructural protein(NS3 serine protease)was revealed in 1996;an infectious clone of HcV complementary DNA was first constructed in 1997;interferon and ribavirin combination therapy was established in 1998 and the therapeutic strategy gradually optimized;the HcV replicon system was produced in1999;functional HcV pseudotyped viral particles were described in 2003;and recombinant infectious HcV in tissue culture was produced successfully in ***,tremendous advances in HcV receptor discovery,understanding the HcV lifecycle,decryption of the HcV genome and proteins,as well as new anti-HcV compounds have been *** HcV is difficult to isolate and culture,researchers have had to avail themselves to the best of modern biomedical technology;some of the major achievements in HcV research have not only advanced the understanding of HcV but also promoted knowledge of virology and cellular *** this review,we summarize the advancements and remaining scotomas in the molecular virology and epidemiology of HcV.

关键词： Hepatitis c virus Hepatitis c virus lifecycle Molecular virology Hepatitis c virus models Epidemiology

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Fatty liver in hepatitis c patients post-sustained virological response with direct-acting antivirals

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World Journal of Gastroenterology 2018年第11期24卷 1269-1277页

作者： Mazen Noureddin Micaela M Wong Tsuyoshi Todo Shelly c Lu Arun J Sanyal Edward A Mena Fatty Liver Program Cedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Digestive and Liver Diseases Cedars-Sinai Medical CenterLos AngelesCA 90048United States california Liver Research Institute PasadenaCA 91105United States comprehensive Transplant center Department of SurgeryCedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Digestive and Liver Diseases Cedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Gastroenterology Hepatology and NutritionDepartment of Internal MedicineSchool of MedicineVirginia Commonwealth UniversityRichmondVA 23298United States

AIM To determine steatosis and fibrosis prevalence in hepatitis c patients after a sustained virological response achieved with direct-acting *** Transient elastography with controlled attenuation parameter(cAP) was used to assess hepatic steatosis post-sustained virological response(SVR);the cAP technology was not available in the United States at study *** stiffness/fibrosis was measured before and 47 wk after treatment *** with genotype 3 and patients with cirrhosis were *** One hundred and one patients were included in the ***-SVR there were decreases from baseline in alanine aminotransferase(ALT)(63.1 to 17.8 U/L),aspartate aminotransferase(51.8 to 21.5 U/L) and fibrosis score(7.4 to 6.1 k Pa)(P cAP;of these,6.25% had advanced *** with steatosis had higher body mass index(29.0 vs 26.1 kg/m2),glucose(107.8 vs 96.6 mg/d L),ALT(20.4 vs 15.3 mg/d L),cAP score(296.3 vs 212.4 d B/m) and fibrosis score(7.0 vs 5.3 k Pa);P compared to baseline,both patients with and without steatosis had change in fibrosis score post-SVR(7.7 k Pa vs 7.0 k Pa and 7.0 k Pa vs 5.3 k Pa);alternatively,(P continued to have clinically significant stiffness(≥ 7 k Pa).cONcLUSION Fatty liver is very common in hepatitis c virus(HcV) patients *** patients continue to have elevated mean fibrosis score(≥ 7 k Pa) compared to those without fatty liver;some have advanced *** term follow up is needed to assess steatosis and fibrosis in HcV patients post-SVR.

关键词： Nonalcoholic fatty liver disease Hepatitis c Fibrosis Steatosis Sustained virological response Direct-acting antivirals

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Natural evolution of hepatitis c virus infection in hemodialysis Tunisian patients and cTLA-4 SNP's

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World Journal of Gastroenterology 2015年第35期21卷 10150-10158页

作者： Leila Ksiaa cheikhrouhou Yousr Lakhoua-Gorgi Imen Sfar Salwa Jendoubi-Ayed Houda Aouadi Mouna Makhlouf Khaled Ayed Taieb Ben Abdallah Immunology Research Laboratory of Kidney Transplantation and Immunopathology Laboratoire de Recherche Laboratory of Immunology Charles Nicolle Hospital

AIM: To analyze the polymorphisms of cTLA-4 gene involved in the response against hepatitis c virus(HcV) ***: We recruited 500 hemodialysed patients from several hemodialysis centers, all HcV-antibody positive, spread over different regions of Tunisia, as part of a national survey in 2008 conducted in the laboratory of immunology at the charles Nicolle hospital Tunisia, classified into two groups G1(PcR+) and G2(PcR-) according to the presence or absence of viral RNA. Of these patients, 307 were followed prospectively on a viral molecular level over a period from 2002 to 2008, divided into two groups based on the persistence and viral clearance. PcR-RFLP was performed for the analysis of SNPs(+49) A/G and(+6230) G/A cTLA-4 for these 500 patients and 358 healthy ***: Analysis of clinical and virological charac-teristics of our cohort suggests a nosocomial infection in our hemodialysed patients with transfusion history as a primary risk factor and a predominance of genotype 1b. The haplotype analysis revealed an increase of frequencies of GG(+49)/(cT60) cTLA-4 in the entire patients group compared to controls(P = 0.0036 and OR = 1.42; 95%cI: 1.12-1.79, respectively). This haplotype is therefore associated with susceptibility to HcV infection. cONcLUSION: Our study suggests a possible role of cTLA-4 polymorphisms in the outcome of HcV infection in the Tunisian hemodialysed population.

关键词： Hepatitis c virus Hemodialysis Natural evolution c

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Aspartate transaminase to platelet ratio index in hepatitis c virus and Schistosomiasis coinfection

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World Journal of Gastroenterology 2015年第46期21卷 13132-13139页

作者： Moutaz Derbala Mohammed Elshiekh Elbadri Aliaa Mohamed Amer Saad Al Kaabi Khaleel Hassan Sultan Yasser Medhat Kamel Eman Hassan Satti Elsayed Tony Yervant Avades Prem chandra Fatma M Shebl Gastroenterology and Hepatology Hamad Medical CorporationHamad General Hospital Gastroenterology and Hepatology Theodor Bilharz Research Institute Medical Department Weill Cornell Medical College Laboratory Medicine and pathology Hematology SectionHamad Medical CorporationHamad General Hospital General Medicine Medical EducationHamad Medical CorporationHamad General Hospital Department of Laboratory Medicine and Pathology Hamad Medical CorporationHamad General Hospital Medical Research center Hamad Medical CorporationHamad General Hospital chronic Disease Epidemiology DepartmentYale School of Public Health

AIM: To assess the diagnostic accuracy,of aminotransferase-to-platelet ratio index(APRI) alone and with antischistosomal antibody(Ab) in patients with hepatitis c virus(HcV) and schistosomiasis coinfection. METHODS: This retrospective study included medical records of three hundred and eighty three Egyptianmen patients who had undergone percutaneous liver biopsy between January 2006 to April 2014 in tertiary care hospital in Qatar for diagnosis or monitoring purpose were selected. Data of patients > 18 years of age were included in the study. The values of HcV RNA titer and antischistosomal antibody titer were also taken into consideration. Patients were excluded from the study if they had any other concomitant chronic liver disease,including; history of previous antiviral or interferon therapy,immunosuppressive,therapy,chronic hepatitis B infection,human immunodeficiency virus co-infection,autoimmune hepatitis,decompensated liver disease,hepatocellular carcinoma,prior liver transplantation,and if no data about the liver biopsy present. RESULTS: Median age of patients was 46 years. About 7.1% had no fibrosis,whereas 30.4%,37.5%,20.4%,and 4.6% had fibrosis of stage Ⅰ,Ⅱ,Ⅲ,and Ⅳ respectively. In bivariate analysis,APRI score,levels of AST,platelet count and age of patient showed statistically significant association with liver fibrosis(P chistosomal antibody titer(P = 0.52) and HcV RNA titer(P = 0.79) failed to show a significant association. The respective AUc values for no fibrosis,significant fibrosis,severe fibrosis and cirrhosis of APRI score were 63%,73.2%,81.1% and 88.9% respectively. This showed good sensitivity and specificity of APRI alone for grading of liver fibrosis. But the inclusion of anti-Schistosoma antibody did not improve the prediction of fibrosis stage. cONcLUSION: The study results suggest that noninvasive biochemical markers like APRI are sensitive and specific in diagnosing the degree of fibrosis and cirrhosis in patient

关键词： Hepatitis c Schistosomiasis Aspartate transaminase

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Epidemiology of hepatitis c in Greece

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World Journal of Gastroenterology 2016年第36期22卷 8094-8102页

作者： christos Triantos christos Konstantakis Paraskeui Tselekouni Maria Kalafateli Ioanna Aggeletopoulou Spilios Manolakopoulos Department of Gastroenterology University Hospital of Patras 2nd Department of Internal Medicine Hippokration General Hospital of Athens

Hepatitis c is a global health issue and constitutes a major cause of chronic liver disease worldwide. In this article, a comprehensive literature search was conducted for the prevalence of hepatitis c virus(HcV) infection in Greece, since data on the HcV prevalence, viremia and genotypes are important for developing strategies to manage or eliminate HcV infection. In addition, the pattern of HcV infection was analyzed according to the geographic region and the risk factors. These differences reflect not only distinct epidemiological characteristics among populations, but also differences on the strategy of data acquisition and quantification. Although there are not enough data, the estimation of the current prevalence of Hepatitis c in Greece ranges from 0.5% to 2%. The most important risk factors for HcV infection include blood product transfusion, intravenous drug use, chronic hemodialysis, organ transplantation, occupational exposure, sexual transmission, and vertical transmission. Because of lack of vaccine or effective post-exposure prophylaxis for HcV, the main focus of prevention is to recognize and control these risk factors. HcV infection in Greece is closely associated with the development of chronic liver disease, cirrhosis, and primary hepatocellular carcinoma. As far as the genotype distribution is concerned genotype 1 estimated to be 45%-47% and it constitutes the prevalent genotype in Greece, followed by genotype 3.

关键词： Prevalence Hepatitis c virus infection Hepatitis c Greece Epidemiology

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Hepatitis c virus genotype 3: Meta-analysis on sustained virologic response rates with currently available treatment options

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World Journal of Gastroenterology 2016年第22期22卷 5285-5292页

作者： Javier Ampuero K Rajender Reddy Manuel Romero-Gomez Inter-centre Unit of Digestive Diseases and cIBERehd Virgen Macarena Virgen del Rocio University Hospitals University of Sevilla 41018 Sevilla Spain Instituto de Biomedicina de Sevilla 41018 Sevilla Spain Division of Gastroenterology and Hepatology Department of Medicine University of Pennsylvania Philadelphia PA 19107 United States

AIM: To address the therapeutic efficacy of various treatment regimens in genotype 3 selecting randomized clinical trials and prospective National cohort ***:(1) PEG-INF-based therapy including sofosbuvir(SOF) + RBV for 12 wk vs SOF + RBV 24 wk;(2) SOF + RBV therapy 12 wk/16 wk vs 24 wk; and(3) the role of RBV in SOF + daclatasvir(DcV) and SOF + ledipasvir(LDV) combinations. This metaanalysis provides robust information with the intention of addressing treatment strategy for hepatitis c virus genotype ***: A combination treatment including SOF + RBV + PEG-IFN for 12 wk notes better SVR than with only SOF + RBV for 12 wk, although its association with more frequent adverse effects may be a limiting factor. Longer duration therapy with SOF + RBV(24 wk) has achieved higher SVR rates than shorter durations(12 or 16 wk). SOF + LDV are not an ideal treatment for genotype 3. cONcLUSION: Lastly, SOF + DcV combination is probably the best oral therapy option and the addition of RBV does not appear to be needed to increase SVR rates substantially.

关键词： Hepatitis c Genotype 3 Sofosbuvir Daclatasvir Ledipasvir

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