Characterization of primary direct-acting antiviral (DAA) drugs resistance mutations in NS5A/NS5B regions of hepatitis C virus with genotype 1a and 1b from patients with chronic hepatitis

ABSTRACT The Hepatitis C virus (HCV) infection is a public health problem. The high level of HCV replication and its lack of post-transcriptional correction mechanisms results in the emergence of viral variants and the difficulty in determining polymorphisms and variants that contain the substitutions associated with resistance towards new antivirals. The main focus of this study was to map the NS5A and NS5B polymorphisms and resistance mutations to new antiviral drugs in HCV strains genotype 1 from patients with chronic hepatitis C infection. Serum samples were collected from patients who underwent routine viral load tests at the Instituto Adolfo Lutz, Sao Paulo city, Brazil. A total of 698 and 853 samples were used for the characterization of NS5A and NS5B regions, respectively, which comprise the HCV genotypes 1a and 1b. The prevalence of resistance mutations found in the NS5A region was 6.4%, with Y93H, L31M, Q30R, and Y93N as the main resistance-associated substitutions (RAS). No NS5B-associated RAS was observed for any of the analyzed drugs. These findings support that the RAS test should be offered to individuals with poor response to double combination regimens prior to treatment initiation, thereby assisting strain vigilance and selection of effective treatment or retreatment options using DAA regimens.

Ongoing rubella epidemic in Osaka, Japan, in 2018–2019

Abstract@#A large rubella epidemic is currently ongoing since 2018 in Osaka, Japan. The detected rubella viruses were classified into genotypes 1E lineage 2 and 2B lineage 1. These strains may have been imported from endemic countries, and these viruses spread within the susceptible population.

Molecular epidemiology of Hepatitis delta virus infection in Minas Gerais state from Brazil, an area outside the hyperendemic region of the Amazon Basin

BACKGROUND Hepatitis delta virus (HDV) infections in hepatitis B virus (HBV) carriers are the most severe form of viral hepatitis. HDV prevalence is high in the Brazilian Amazon, but studies in other regions of the country are still scarce and often underestimated its prevalence by including a small numbers of individuals. OBJECTIVE This study aimed to determine the serological prevalence of hepatitis D, the genotypes circulating and to evaluate the associated risk factors for acquisition of HDV in Minas Gerais state, Brazil. METHODS We screened plasma samples (n = 498) from HBV chronic carriers for anti-HD antibodies using a commercial enzyme-linked immunosorbent assay (ELISA) kit. For those samples that were positive for anti-HD antibodies, we performed a reverse transcriptase (RT) nested-polymerase chain reaction (nested-PCR) in order to detect the viral genome and identify the viral genotypes circulating in the state. FINDINGS The prevalence was 6.22% (31/498). Blood transfusion was the only risk factor associated with HDV infection [risk ratio: 3.73; 95% confidence interval (CI): 1.44 to 9.65]. For 26 anti-HD positive patients, HDAg gene sequences were determined and in all patients HDV genotype 1 was found. CONCLUSIONS This study confirmed the circulation of HDV in Minas Gerais, an area previously considered non-endemic for hepatitis D in Brazil. The prevalence found in this study is much higher when compared to other studies performed in Brazil, probably because the population in our study was selected with minimal bias. Furthermore, in 26 anti-HD positive plasma samples, we were also able to detect the viral genome, indicating that these patients were experienced an active infection at the time of sample collection. These findings emphasise the importance of anti-HD testing in HBV infected individuals, which may contribute to this disease control in Brazil.

Efficacy of precision therapy with direct-acting antiviral drugs for patients with chronic HCV genotype 1b infection / 中华临床感染病杂志

Objective To evaluate the efficacy of precision therapy with direct-acting antiviral drugs (DAAs) for patients with chronic HCV gene type 1b infection.Methods One hundred and thirteen patients with chronic HCV genotype 1b infection admitted in the Department of Infectious Diseases of First Hospital of Shanxi Medical University from January 2018 to July 2019 were enrolled,including 89 patients with chronic hepatitis and 24 patients with cirrhosis.Different DAAs therapeutic schedule were taken based on liver function, kidney function, complication and treatment costs.Seventy-two patients were treated with pan-genotype drugs, including 43 patients treated with Sofosbuvir and Velpatasvir (SOF+VEL), 13 treated with Sofosbuvir and Ribavirin ( SOF +RBV), and 16 treated with Sofosbuvir and Daclatasvir ( SOF +DCV).Forty one patients were treated with specific genotype DAAs , including 15 treated with Ombitasvir and Dasabuvir (OBV+DSV), and 26 treated with Elbasvir and Grazoprevir tablets (EBR+GZR).Pair t test and Chi-square test were used to compare virological response rate , the liver function and the adverse reactions were observed.Results The super-rapid virological response (SRVR) rate with DAAs treatment at 1 week was 88.5%(100／113),and the rapid virological response ( RVR) at 4 weeks of treatment was 98.2%(111／113).There was no significant differences in SRVR and RVR among the patients treated with five treatment regimens (χ2 ＝5.95 and 1.04,P＞0.05), all the patients obtained complete early virological response (CEVR) at 12 weeks and sustained virological response ( SVR12) at 12 weeks after treatment. Besides, there were no significant differences in SRVR and RVR between pan-genotype and gene-specific drugs (χ2 ＝0.03 and 0.17, P＞0.05),both CEVR and SVR12 reached 100% in all patients.The liver transaminase levels were improved in patients undergoing pan-genotype or gene-specific drugs treatment. Mild adverse reactions were observed in 5 cases, hemolysis occurred in 1 patient and it was cured after replacement of drugs.Conclusion Both pan-genotype and specific genotypes of DAAs can achieve high virological response rates.Genotypic testing should be performed before antiviral therapy , in order to accurately select treatment options and to save costs.

Efficacy and safety of yimitasvir phospha combined with sofosbuvir in patients with chronic hepatitis C virus infection / 中华传染病杂志

Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.

The Real-World Safety and Efficacy of Daclatasvir and Asunaprevir for Elderly Patients

BACKGROUND/AIMS: Although daclatasvir with asunaprevir was approved in Japan for interferon ineligible or intolerant patients, patients aged ≥75 years were excluded in the phase III trial. The present study aimed to evaluate the safety and efficacy of this therapy for elderly patients aged ≥75 years and to clarify whether an extremely high sustained virological response (SVR) rate can be achieved, even in a real-world setting when patients with resistance-associated substitutions (RASs) to nonstructural protein 5A (NS5A) inhibitors or prior simeprevir failure are excluded. METHODS: Daclatasvir (60 mg) and asunaprevir (100 mg) were orally administered daily for 24 weeks. Patients without pre-existing NS5A RASs and simeprevir failure were enrolled in this study. RESULTS: Overall, 110 patients were treated. The median age was 73 years old. The SVR rates of total patients, those aged ≥75 years, and those aged < 75 years were 97% (107/110), 98% (46/47), and 97% (61/63), respectively. The treatment of two patients (2%) was discontinued because of adverse events. CONCLUSIONS: Daclatasvir with asunaprevir was a safe treatment, even in patients aged ≥75 years. When patients without pre-existing NS5A RASs and prior simeprevir failure were selected, an extremely high SVR rate could be achieved irrespective of age.

Comparison of simeprevir versus telaprevir plus pegylated interferon alfa and ribavirin in patients with hepatitis C virus genotype 1 infection——a meta-analysis / 中华传染病杂志

Objective To compare the efficacy and safety of simeprevir-based (SMV) or telaprevir-based (TVR) triple therapy [SMV + Pegylated interferon alfa (PegIFNα) and ribavirin (RBV) versus TVR + PegIFNαand RBV] in patients with hepatitis C virus (HCV) genotype 1 infection .Methods A systematic literature searching was conducted in multiple online databases to identify relevant studies .The sustained virologic response rate at 12 (SVR12) and 24 weeks (SVR24) after end of the treatment were used as the efficacy endpoints .The rate of treatment related adverse events (AEs) ,discontinuation due to AEs and overall treatment discontinuation were used as safety endpoints . Patients were divided into multiple subgroups according to the previous treatment history to further compare the efficacy of the two treatment regimen .Statistical analyses were performed using the RevMan 5 .3 software .The Jajad score scale and the Newcastle-Ottawa scale were employed to evaluate the quality of included studies .Results A total of 5 clinical studies including 1666 HCV genotype 1 patients were included in this study .The pooled results showed that SVR12 rates in SMV group and TVR group were 67 .6％ and 68 .3％ , respectively .There was no significant difference in overall SVR12 rate between SMV and TVR groups (OR=0 .95 ,95％ CI:0 .76 -1 .18 , P=0 .65) .There was no significant heterogeneity among studies (P=0 .84 ,I2 = 0％ ) .For SVR24 rate ,the average SVR24 rate in SMV group was 78％ ,which was lower than that in TVR group of 84％ .However ,there was no significant difference in overall SVR24 rate between SMV and TVR groups (OR=0 .71 ,95％ CI:0 .42-1 .20 ,P=0 .20) .Meanwhile ,there was no significant heterogeneity among studies (P= 0 .69 ,I2 = 0％ ) .The subgroup analysis also showed that there was no significant difference in efficacy between SMV and TVR-based triple therapy for treatment-native patients ,prior partial response ,relapse ,and prior null response patients (all P>0 .05) .However , the pooled analysis indicated that both SMV-based and TVR-based triple therapies were most effective for the treatment-naive patients(SMV :85 .7％ ,TVR :85 .6％ ) .For the safety endpoints ,the incidence rate of anemia was significant lower in SMV group compared to TVR group (OR=0 .30 ,P<0 .001) .For the rate of overall treatment discontinuation ,there was no statistically significant difference between SMV and TVR group (OR=0 .48 ,P=0 .12) .Conclusions This meta-analysis suggests that the efficacy of SMV-based triple therapy is non-inferior to TVR-based triple therapy .However ,the SMV-based triple therapy is more tolerable and has a lower incident rate of anemia and discontinuation due to AEs compared to TVR-based triple therapy .

Analysis on genetic characteristics of rubella virus isolates from 2011 to 2017 in Shanghai, China / 中华实验和临床病毒学杂志

Objective@#To analyze the molecular epidemiological characteristics of rubella virus wild strains isolated in Shanghai during 2011-2017.@*Methods@#Throat swabs were collected from suspected measles or rubella patients in Shanghai during 2011-2017, which were identified as rubella and excluded measles by laboratory tests. Throat swabs were used to conduct cell culture for rubella virus isolation. After identification by RT-PCR, the nucleic acid of gene E1 of rubella virus was amplified and sequenced, followed by molecular epidemiological analysis.@*Results@#Totally 395 strains of rubella virus were isolated from 684 throat swabs. Compared 377 isolates with the WHO reference strains of all genotypes, phylogenetic tree was constructed based on the amplified 739 nucleotides sequences. These isolates were characterized as two genotypes respectively, 109 strains were defined as genotype 1E which were closer to the WHO reference strain from China (RVi/Shandong.CHN/0.02/), and others were genotype 2B while 5 strains of them were defined as a lineage. Most of the nucleotide mutations were nonsense mutation, and the amino acid sequences were highly conserved. All the genotype 1E rubella viruses except one strain had the same mutation at aa338 site.@*Conclusions@#Two genotypes of rubella virus circulated in Shanghai during 2011-2017.Genotype 1E appeared to be the predominant genotype during 2011-2013, genotype 2B was continuously existing since being found in 2011 and appeared to be the predominant genotype during 2014-2016.

Daclatasvir Plus Asunaprevir for the Treatment of Patients with Hepatitis C Virus Genotype 1b Infection: Real-World Efficacy, Changes in Liver Stiffness and Fibrosis Markers, and Safety

BACKGROUND/AIMS: The treatment with daclatasvir plus asunaprevir (DCV+ASV) is associated with potent antiviral effects in patients with genotype 1b hepatitis C virus (HCV) infection. We investigated the real-world efficacy, changes in liver stiffness and noninvasive fibrosis markers, and the safety of DCV+ASV treatment in Korean patients. METHODS: In total, 363 patients with chronic hepatitis C were treated with DCV+ASV between August 2015 and January 2017. Finally, we analyzed the data of 270 patients who were monitored for at least 12 weeks after the end of treatment. RESULTS: The mean age was 60.7 years, and females predominated (60.4%). Most patients (64.8%) were treatment-naïve, and 56 patients (20.7%) had cirrhosis. Two hundred fifty-seven (95.2%) and 251 (93.0%) patients achieved end-of-treatment responses and sustained virological responses at 12 weeks posttreatment (SVR12), respectively. The SVR12 rates were higher in patients who were < 65 years of age, males, without cirrhosis and had lower HCV RNA levels. All LS values and fibrosis-4 and aspartate aminotransferase-to-platelet ratio index values declined from baseline to the time of assessment of SVR12. CONCLUSIONS: The DCV+ASV therapy resulted in a high SVR12 and improved liver fibrosis; the treatment was well tolerated in patients with genotype 1b HCV infections.

Efficacy and Safety of Simeprevir Plus Ribavirin/Pegylated-Interferon for the Treatment of Hepatitis C Virus Genotype 1: A Meta Analysis / 中国药学杂志

OBJECTIVE: To assess efficacy and safety of simeprevir-based therapy for the treatment of hepatitis C virus genotype 1. METHODS: We searched Pubmed, EMBASE, the Cochrane Library, highwire, CBM, CNKI, Wanfang, VIP Database and literature from some relative paper based magazines also be retrieved. Randomised controlled trials(RCTs)of examining simeprevir plus ribavirin(RBV) and pegylated-interferon(peg-IFN) among adults with chronic HCV infection were included.Select the RCTs according to the inclusion criterion, then appraise them critiically by Cochrane handbook. All outcomes were pooled by the RevMan5.2 software of Cochrane Collaboration. Data were extracted on virological responses including sustained virological response at post-treatment week 12(SVR12), SVR24, serious adverse event(SAE),treat-ment discontinuation due to an adverse event(TDAE). RESULTS: Eight RCTs were finally included involving 2 758 patients who were treated with simeprevir, RBV and peg-IFN. The RESULTS of Meta-analysis showed that SVR12 rates was[OR=3.92,95%CI(2.86,5.39), P<0.000 01], SVR24 rates was[12 week:OR=3.79,95%CI(2.86,5.01), P<0.000 01], [24 week:OR=4.12,95%CI(2.69,6.30), P<0.000 01], SAE rates was[12 week:OR=0.67,95%CI(0.47,0.95),P=0.02], TDAE rates was[12 week:OR=0.85, 95%CI(0.54, 1.33), P=0.48],[24 week:OR=0.82,95%CI(0.42,1.60), P=0.55]. CONCLUSION: Evidence shows that, simeprevir-based treatment(simeprevir plus ribavirin and pegylated-interferon)for treating genotype 1 chronic HCV infection is better than PR treatment in SVR12 rates,SVR24 rates and SAE rates(course of treatment is 12 weeks). However, they are alike in TDAE rates.

Results of ledipasvir/sofosbuvir treatment on with HCV genotype 1b infection / Монголын Анагаах Ухаан

IntroductionGenotype 1 infection has been historically difficult to treat, but multiple recent studies have showntreatment results greater than high in these genotype 1b patients using well-tolerated, all-oral regimensconsisting of new direct-acting antiviral agents.GoalPurpose of the study was to define the effects of ledipasvir/sofosbuvir treatment on patients with HCVgenotype 1b infection.Materials and MethodsIn this study we enrolled 2 treatment-naive and 66 treatment-experienced, totally 68 patients who tookledipasvir/sofosbuvir during the period from January 2016 to March 2016. We used randomly selectedand double-blinded method in our clinical research. The descriptive and non-parametrical statisticaltests were conducted using SPSS Statistics 20.0.ResultsThe SVR12 and SVR24 rates were greater than 95% and no differences were observed in treatmentnaiveversus treatment-experienced patients.ConclusionTheSVR12 rates were found in 98.6% while the SVR24 was in 97.1% of 68 patients. Only 2.9% of thetotal cases were appeared relapse of HCV infection. These findings indicated needs of further studieson long-term effects of ledipasvir/sofosbuvir.

Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Treatment of Chronic Hepatitis C Genotype 1 / 대한소화기학회지

The introduction of direct-acting antiviral agents (DAAs) has markedly improved the sustained virological response (SVR) rates in patients with chronic hepatitis C. Currently, four classes of DAAs targeting three HCV proteins (NS3, NS5A, and NS5B) have been approved for treatment in many countries. Since drugs show advantages and disadvantages, use of a combination of two or more DAAs with different targets or addition of ribavirin in a difficult-to-treat patient shows an SVR rate of ~90% after 12 weeks of treatment or expanded treatment for 24 weeks. Various types of DAA are awaiting approval which will improve the treatment of chronic hepatitis C virus genotype 1 infection. However, high costs, drug resistance and interactions between various drugs remain to be overcome. With further advances in the development of antiviral agents, it could be expected that in the near future, there will be DAAs that are affordable and cost effective, require shorter treatment duration, effective in a broad range of patients, and have less side effects and drug-drug interactions.

Parvovirus B19 1A complete genome from a fatal case in Brazil

Parvovirus B19 (B19V) infects individuals worldwide and is associated with an ample range of pathologies and clinical manifestations. B19V is classified into three distinct genotypes, all identified in Brazil. Here, we report a complete sequence of a B19V genotype 1A that was obtained by high-throughput metagenomic sequencing. This genome provides information that will contribute to the studies on B19V epidemiology and evolution.

Early predictive efficacy of core antigen on antiviral outcomes in genotype 1 hepatitis C virus infected patients

Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expen- sive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen) had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%), and hepatitis C virus core antigen decrease greater than 1 log10 IU/mL (early virological response based on hepatitis C virus core antigen) had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.Z%). Analysis on the validation group demonstrated a positive predictivevalue of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to hepatitis C virus RNA in predicting sustained virologic response of chronic genotype 1 hepatitis C virus infected patients, and can be used to guide anti-hepatitis C virus treatment, especially in resource-limited areas.

Tendencia preliminar del polimorfismo rs12979860 il28b en la población mestiza venezolana / Preliminary tendency of rs12979860 il28b polymorphism in the mestizo Venezuelan population

Introducción: El polimorfismo de un solo nucleótido (SNP) rs12979860 en el gen IL28B del cromosoma 19 que codifica al interferón (IFN)-λ-3, se asocia con respuesta viral sostenida a la terapia combinada de IFN-α pegilado y ribavirina en pacientes con virus de hepatitis C (VHC) genotipo 1. La diferencia alélica de este polimorfismo difiere entre grupos étnicos. Objetivo: Comparar las frecuencias alélicas (FA) y genotípicas (FG) del SNP rs12979860 del gen IL28B entre individuos sanos y pacientes con VHC mestizos venezolanos. Material y métodos: De 34 pacientes con VHC genotipo 1 investigados para este polimorfismo, solamente 19 eran venezolanos de tercera generación, a quienes comparamos con 19 individuos sanos conocidos mestizos. La determinación del polimorfismo se realizó mediante el ensayo TaqMAN SNP empleando el sistema de PCR-tiempo real. Resultados: El alelo más prevalente en la población sana fue el alelo silvestre C (55%) y en los pacientes la frecuencia fue igual para el alelo C y para el alelo mutado T (50%) sin diferencia significativa entre las dos poblaciones. El genotipo predominante fue el heterocigoto (C/T) en pacientes y en controles (80% y 58%) evidenciándose mayor valor en el primer grupo pero no llegando a ser significativo. Predominando en controles vs pacientes se aprecian los genotipos homocigotos C/C (26% vs 10%) y T/T (16% vs 10%). Conclusión: La tendencia preliminar apunta al genotipo heterocigoto C/T del gen IL28B como el más frecuente en la población mestiza venezolana.

Introduction: Single-nucleotide polymorphism (SNP) rs12979860 in the region of the IL28B gene on chromosome 19, coding for the interferon (IFN)-λ-3 are associated with sustained viral response to combined therapy with pegylated IFN-α and ribavirin in patients with hepatitis C virus (HCV) genotype 1. Allelic difference from this polymorphism varies among ethnic groups. Objective: To compare allelic frequencies (AF) and genotypes frequencies (GF) of SNP rs12979860 of the IL28B gene between healthy individuals and mestizos Venezuelan HCV patients. Material and Methods: From 34 patients with HCV genotype 1 investigated for this polymorphism only 19 were third generation mestizo Venezuelan patients who were compared to 19 healthy individuals known mestizos. SNP determination was carried-out by TaqMAN SNP assay employing real-time PCR system. Results: Most prevalent allele in the healthy population was the C wild (55%) while in patients similar frequency was found for C allele or the mutant allele (50% each) with no significant difference. The heterozygote genotype (C/T) was predominant in patients and controls (80% and 58%) with a higher value for the former group but without significance. Homozygote genotypes were more prevalent in controls vs. patients: C/C (26% vs. 10%) and T/T (16% vs. 10%). Conclusion: Preliminary tendency points-out that heterozygote genotype C/T from the IL28B gene is the most frequent in the Venezuelan mestizo population.

Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors

The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.

Genetic characterization of rubella virus isolated in Guizhou province in 2012 / 重庆医学

Objective To identify the rubella virus circulated in Guizhou province in 2012 ,and confirm the genotype and analyze the genetic characterization of rubella virus isolated .Methods The throat swab samples were collected from suspected rubella cases during the rubella outbreak and sporadic in 2012 .Rubella virus isolation was performed using Vero/SLAM cells .The presence of vi-ral RNA was detected using real-time RT-PCR after RNA extraction from infected tissue culture cells .Fragments of 944 nucleotides of E1 genes of the isolates were amplified by RT-PCR ,the PCR products were directly sequenced and analyzed .The phylogenetic trees based on the 739 nucleotide sequences 1E was conducted with the rubella viruses isolated in Guizhou province in 2012 and 32 WHO reference sequences representing 13 genotypes .Results 5 rubella virus strains were isolated in Guizhou province for the first time .The results of phylogenetic analysis showed that all 5 rubella virus isolates belong to genotype 1E .The nucleotide acid and a-mino acid homology among 5 rubella virus isolates were 99 .8% -100 .0% and 100 .0% respectively .Compared with the WHO ref-erence strain (Chinese strain T14-CH-02) ,the nucleotide acid and amino acid homology were 98 .7% -98 .9% and 100 .0% respec-tively ;while compared with another WHO reference strain (Malaysia strains M1-MAL-01) ,the nucleotide acid and amino acid ho-mology were 97 .5% -97 .6% and 99 .5% .Conclusion Genotype 1E rubella virus was the predominant genotype in Guizhou prov-ince in 2012 ,which was similar to the other provinces .This study accumulated the molecular epidemiological baseline date in Guizhou province .

Impact of ribavirin dose reduction during treatment in chronic hepatitis C genotype 1 patients

No abstract available.

Metabolic syndrome in patients with chronic hepatitis C virus genotype 1 infection who do not have obesity or type 2 diabetes

OBJECTIVE: The individual components of metabolic syndrome may be independent predictors of mortality in patients with liver disease. We aimed to evaluate the prevalence of metabolic syndrome and its related components in hepatitis C virus-infected patients who are not obese and do not have type 2 diabetes. METHODS: This cross-sectional study included 125 patients infected with hepatitis C virus genotype 1. Metabolic syndrome was defined according to the International Diabetes Federation. Anthropometric data were measured according to standardized procedures. Bioimpedance analysis was performed on all patients. RESULTS: Metabolic syndrome was diagnosed in 21.6% of patients. Of the subjects with metabolic syndrome, 59.3% had hypertension, 77.8% had insulin resistance, 85.2% were overweight, 48.1% had a high waist circumference, 85.2% had an increased body fat percentage, and 92.3% had an elevated waist:hip ratio. In the bivariate analysis, female sex (OR 2.58; 95% CI: 1.09-6.25), elevated gamma-glutamyl transferase (γGT) (OR 2.63; 95% CI: 1.04-7.29), elevated fasting glucose (OR 8.05; 95% CI: 3.17-21.32), low HDL cholesterol (OR 2.80; 95% CI: 1.07-7.16), hypertriglyceridemia (OR 7.91; 95% CI: 2.88-22.71), elevated waist circumference (OR 10.33; 95% CI: 3.72-30.67), overweight (OR 11.33; 95% CI: 3.97-41.07), and increased body fat percentage (OR 8.34; 95% CI: 2.94-30.08) were independent determinants of metabolic syndrome. Using the final multivariate regression model, similar results were observed for abdominal fat (OR 9.98; 95% CI: 2.63-44.41) and total body fat percentage (OR 8.73; 95% CI: 2.33-42.34). However, metabolic syndrome risk was also high for those with blood glucose >5.55 mmol/L or HDL cholesterol <0.9 mmol/L (OR 16.69; 95% CI: 4.64-76.35; OR 7.23; 95% CI: 1.86-32.63, respectively). CONCLUSION: Metabolic syndrome is highly prevalent among hepatitis C virus-infected patients without type 2 diabetes or obesity. Metabolic syndrome was significantly associated with hypertension, insulin resistance, increased abdominal fat, and overweight.

Alfapeguinterferon-2a e ribavirina versus alfapeguinterferon-2b e ribavirina: avaliação custo-efetividade e do impacto orçamentário do tratamento do genótipo 1 da hepatite C crônica / Alfa-pegylated interferons (2a and 2b) and ribavirin for treatment chronic hepatitis C, genotype 1: a cost-effectiveness analysis

Foi realizada análise de custo-efetividade e do impacto orçamentário de tratamentos indicados para adultos infectados com genótipo 1 do vírus da hepatite C, comparando o não-tratamento com terapias combinadas de alfapeguinterferon-2a e 2b associados a ribavirina. O modelo de Markov desenvolvido projetou a evolução da hepatite C em coorte de 1.000 pacientes, por um período de 30 anos, para os vários estados do desenvolvimento da doença. As terapias combinadas da ribavirina com o alfapeguinterferon 2a ou 2b apresentam efetividades estatisticamente idênticas quando avaliadas em 30 anos de evolução da doença. Quanto ao impacto do tratamento nos anos de vida e nos anos de vida ajustados por qualidade de vida; os anos de vida ganhos por qualidade de vida em relação à evolução da doença sem tratamento foram de 1,67 e 1,63, respectivamente, para a terapia combinada com alfapeguinterferon 2a e 2b, aplicando-se 5 por cento de desconto. A estratégia de tratamento com alfapeguinterferon 2a mais ribavirina se revelou mais custo-efetiva, dominando a outra alternativa de tratamento. Embora não haja diferenças significativas de efetividade entre os dois tipos de alfapeguinterferon, a diferença de preço entre os dois medicamentos faz com que a alternativa do uso do alfapeguinterferon 2a mais ribavirina seja mais eficiente. Quanto à estimativa do impacto orçamentário para o período de 2008 a 2017, a utilização do alfapeguinterferon 2a mais ribavirina resulta em redução nos gastos de aproximadamente 19 por cento, caso todos os doentes fossem tratados utilizando-se os esquemas terapêuticos selecionados.

A cost-effectiveness and budget impact of treatments given to adults infected with genotype 1 hepatitis C virus was performed by comparing the non-treatment with combined therapy alfapeguinterferon-2a and 2b and ribavirin. The Markov model developed engineered the development of hepatitis C in a cohort of 1,000 patients for a period of 30 years for the various states of disease development. The combined therapy of ribavirin with alfapeguinterferon 2a or 2b have statistically identical effectiveness when evaluated at 30 years of disease. As for the impact of treatment in life years and years of life adjusted for quality of life, the life years gained for quality of life in relation to the evolution of the disease without treatment were 1.67 and 1.63, respectively, for combined therapy with alfapeguinterferon 2a and 2b, applying a 5 percent discount. The strategy of treatment with alfapeguinterferon 2a plus ribavirin was more cost-effective, dominating the other treatment. Although there are significant differences in effectiveness between the two types of alfapeguinterferon, the price difference between the two products makes the alternative of using alfapeguinterferon 2a plus ribavirin more effective. Concerning the estimated budget impact for the period 2008 to 2017, using alfapeguinterferon 2a plus ribavirin results in a reduction in spending of about 19 percent if all patients were treated using the selected treatment regimens.