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Late presentation to care is the major obstacle to receiving treatment for chronic hepatitis C (CHC). Our aim was to analyze the prevalence and trends of late presenters (LP) at first consultations in Croatia during a 10-year period. This retrospective cross-sectional study included all adult CHC patients (n = 854) entering specialist medical care at the University Hospital for Infectious Diseases Zagreb between 2009 and 2018. LP was defined as liver stiffness measurement &ge, 9.5 kPa or biopsy METAVIR F &ge, 3. During the study period, mean patients&rsquo, age increased from 37 to 52 years while HCV genotype distribution changed leading to the replacement of genotype 1b with 1a (g1b 32% to 21%, g1a 19% to 38%). A total of 320 (37.4%) were LP, they were older (47.5, IQR 40.5&ndash, 57.6), and more commonly infected with g1b (34.1%) and g3 (42.5%). The prevalence of LP significantly increased from 31.9% in 2009 to 46.5% in 2018. Late presentation for care of CHC is increasing in Croatia suggesting a gap of diagnosing strategies in patients over 50 years.

The transmission of direct-acting antiviral resistance-associated substitutions (RAS) could hamper hepatitis C virus (HCV) cure rates and elimination efforts. A phylogenetic analysis of 87 men who have sex with men recently infected with HCV genotype 1a placed one-third (28/87) in a large cluster, in which 96% harbored NS5A M28V RAS. ispartof: CLINICAL INFECTIOUS DISEASES vol:71 issue:8 pages:E215-E217 ispartof: location:United States status: published

Objective. Cost-effectiveness analysis (CEA) of elbasvir in combination with grazoprevir (EBR/GZR) for the treatment of patients with chronic hepatitis C (CHC), infected with genotype 1 subtype b, who previously did not receive antiviral therapy (AVT), without cirrhosis or with compensated cirrhosis, from a Russian healthcare system perspective. Methods. In a model, developed in MS Office (Microsoft Excel® package), the differences in direct medical costs were determined (using cost minimization analysis) by comparing EBR/GZR and 3D (the combination of ombitasvir, paritaprevir, ritonavir, and dasabuvir), which have comparable effectiveness in patients with chronic hepatitis C (genotype 1b). Besides, changes in costs for the treatment of patients with CHC (genotype 1b), if EBR/GZR are reimbursed, are analysed under the State-guaranteed benefit package (SGBP) for free medical care for the citizens of the Russian Federation (budget impact analysis). Frequencies of long-term consequences of CHC (number of cases of decompensated cirrhosis and hepatocellular carcinoma) were projected in the long run depending on whether AVT is administered or not, for 20 years or lifetime time horizon. For calculations, data from literature and standard financial expenditures in Russian healthcare system in 2018 were used. Univariate (one-way) sensitivity analysis was conducted to assess the impact in the price change of EBR/GZR package on the results of the analysis. Results. Average cost per patient for therapy with EBR/GZR was 510 142 rubles, or 21% less than for therapy with 3D that was 645 614 rubles. If EBR/GZR are included in Vital and Essential Drugs List (VED), expenditures under SGBP for treatment of CHC (genotype 1b) are expected to decrease by 16,1% in three years: by 9,4% in the first year, 15,7% in the second year and by 21% in the third year. Conclusions: Using EBR/GZR in clinical practice is efficient and leads to an improvement in the competitiveness in the field. It also allows reducing the additional healthcare system expenditures on direct-acting antiviral agents (DAAA) in AVT of CHC, and provides highly-effective therapeutic regimes under SGBP for patients without increasing the budget. Greater accessibility of DAAA (EBR/GZR and 3D) within the Russian healthcare system and increased availability of these drugs for the patients will lead to a significant decrease in incidence of such severe and costly consequences of hepatitis as decompensated cirrhosis and hepatocellular carcinoma in comparison with no treatment in the long run.

An unprecedented series of organometallic HCV (hepatitis C virus) NS5A (nonstructural 5A protein) replication complex inhibitors that incorporates a 1,1′-ferrocenediyl scaffold was explored. This scaffold introduces the elements of linear flexibility and non-planar topology that are unconventional for this class of inhibitors. Data from 2-D NMR spectroscopic analyses of these complexes in solution support an anti (unstacked) arrangement of the pharmacophoric groups. Several complexes demonstrate single-digit picomolar in vitro activity in an HCV genotype-1b replicon system. One complex to arise from this investigation (10a) exhibits exceptional picomolar activity against HCV genotype 1a and 1b replicons, low hepatocellular cytotoxicity, and good pharmacokinetic properties in rat.

Highlights • Routine strategies for hepatitis C virus (HCV) genotyping have several limitations. Deep sequencing methods can solve this problem. • Accurate determination of viral genotypes and subtypes would allow optimal patient management and the most effective therapy. • Mixed infections may represent a key factor for efficient therapy. Patients infected with more than one HCV genotype (mixed infection) can be detected only by deep sequencing methods. • These patients can fail treatment with direct-acting antiviral agents, hence next-generation sequencing methods are highly recommended in clinical practice., Background The effectiveness of the new generation of hepatitis C treatments named direct-acting antiviral agents (DAAs) depends on the genotype, subtype, and resistance-associated substitutions present in individual patients. The aim of this study was to evaluate a massive sequencing platform for the analysis of genotypes and subtypes of hepatitis C virus (HCV) in order to optimize therapy. Methods A total of 84 patients with hepatitis C were analyzed. The routine genotyping methodology for HCV used at the study institution (Versant HCV Assay, LiPA) was compared with a deep sequencing platform (454/GS-Junior and Illumina MiSeq). Results The mean viral load in these HCV patients was 6.89 × 106 ± 7.02 × 105. Viral genotypes analyzed by LiPA were distributed as follows: 26% genotype 1a (22/84), 55% genotype 1b (46/84), 1% genotype 1 (1/84), 2.5% genotype 3 (2/84), 6% genotype 3a (5/84), 6% genotype 4a/c/d (5/84). When analyzed by deep sequencing, the samples were distributed as follows: 27% genotype 1a (23/84), 56% genotype 1b (47/84), 8% genotype 3a (7/84), 5% genotype 4d (4/84), 2.5% genotype 4f (2/84). Six of the 84 patients (7%) were infected with more than one subtype. Among these, 33% (2/6) failed DAA-based triple therapy. Conclusions The detection of mixed infection could explain some treatment failures. Accurate determination of viral genotypes and subtypes would allow optimal patient management and improve the effectiveness of DAA therapy.

Chronic hepatitis C infection (HCV) is a common problem in patients with kidney disease (Corouge M. et al. Liver Int (2016); 36:28–33, Fabrizi F. et al. Int. J. Artif. Organs (2017); 0). In the past, treatment of hepatitis C infection was very difficult due to poor efficacy, significant side effects, and the multiple comorbidities that affect patients with advanced kidney disease (Pockros PJ et al. Gastroenterology (2016); 150:1590–1598). Significant recent advances in oral interferon-free treatment regimens allow patients with hepatitis C to be treated effectively with minimal side effects. For patients with genotype 1a, 1b, or 4, there are several recommended oral regimens that achieve virologic cure in greater than 95% of patients, even in patients with severe or end-stage renal disease. For other genotypes, specifically 2, 3, 5, and 6, treatment with direct acting antiviral (DAA) agents that are used in patients with normal renal clearance has significant potential for side effects and is not recommended. Patients who are waiting for a kidney transplant or who have received a kidney transplant and have estimated eGFR greater than 30 ml/min can be treated with multiple regimens in an attempt to cure their hepatitis C (Fabrizi F. et al. Int. J. Artif. Organs (2017); 0). Patients with kidney-related complications due to their chronic hepatitis C infection can also be treated with a significant chance of resolution of the complication (Corouge M. et al. Liver Int (2016); 36:28–33, Kamar N. et al. Clin. Nephrol (2008); 69:149–160). The timing of HCV treatment and kidney transplant depends on the individual transplant centers protocol and the patient’s position on the waiting list for a kidney (Fabrizi F Clin. Liver Dis 2005; 9: 503, viii). USA transplant centers in order to reduce the time on the waiting list have decided to offer HCV-infected patients a kidney from an HCV-positive donor. Treatment of the HCV is then done early after recovery from the transplant surgery. Due to significant advances in developing oral direct acting antiviral agents, we now have safe and effective oral regimens to treat HCV-infected patients with renal disease, including those on hemodialysis, waiting for a kidney transplant, or after a renal transplant. The purpose of this review is to summarize the currently recommended treatment regimens and provide clinicians with guidance in terms of the efficacy and safety of the new direct acting antiviral agents (DAAs) in treating HCV-infected patients who have advanced kidney disease.

Background/Aims: Distribution of Hepatitis C virus (HCV) genotypes vary geographically and may associate with the mode of transmission. Little is known about the molecular epidemiology of HCV infection in Guangzhou, China. Methods: A cross-sectional survey included 561 subjects with chronic HCV infection registered at Nanfang Hospital, Southern Medical University, was performed. All residents were invited for a questionnaire interview to collect information about their personal status and commercial blood donation history. Results: A total of 463 chronic hepatitis C (CHC) patients were finally enrolled. Among the 463 samples, 426 were characterized by partial core-E1 sequences and classified into 7 subtypes: 1b (n=263, 61.7%), 6a (n=86, 20.2%), 2a (n=26, 6.1%), 3b (n=26, 6.1%), 3a (n=22, 5.2%), 6u (n=2, 0.5%), and 4a (n=1, 0.2%). Analysis of genotype-associated risk factors revealed that blood donation and transfusion were strongly associated with subtypes 1b and 2a, while genotype 3b and 6a were more frequent in intravenous drug users. Conclusions: Phylogeographic analyses demonstrated that the distribution of HCV genotypes in Guangzhou is complex. Interestingly, 6a has become a local endemic in Guangzhou and may be the second source region to disseminate 6a to other provinces.

OBJECTIVES: Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice. METHODS: Retrospective analysis of hepatitis C virus (HCV) patients aged >= 65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C). RESULTS: Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65-74 years, 211 (17%) were aged 75-79 years, and 86 (7%) were aged >= 80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin = 75 years (2.59 (1.16-5.83); P = 0.02) and albumin = 75 years) or those with advanced liver disease (albumin

Spontaneously occurring resistance may impair the success of protease inhibitors based regimens in HCV treatment. This study aimed to evaluate associations between amino acid substitutions in NS3/NS4A domain and clinical features of 247 HCV mono or HCV/HIV co-infected patients. Fourteen samples (5.7%) harbored at least one resistance-associated substitution (RAS). The following RASs were detected in NS3 region: T54S (6-2.4%), V55A (7-2.8%), and Q80R (2-0.8%). S122G occurred in 86.9% of HCV genotype 1b samples with either natural polymorphisms or RASs. Advanced liver fibrosis and HIV co-infection were not related to NS3/NS4A amino acid substitutions.

Today liver damage caused by Hepatitis C Virus (HCV) is widespread and included in the list of diseases of a social character. The aim of this research is to identify the peculiarities and summarize the epidemiological characteristics of HCV-infection in Ukraine, based on a retrospective analysis of detecting HCV based on antibodies, RNA and its genotyping, taking into account the sex and age of infected people in regions of Ukraine and particularly in Dniprо and Dnipropetrovs’k region. The research materials were provided by sampling the results of screening tests and qualitative detection of RNA-HCV genotyping (1a, 1b, 2 and 3). The survey involved 10,394 people from different regions of Ukraine (2014–2016). HCV-infection was detected in 3,436 of them, accounting on average for 32.5% of those surveyed. We analysed further 1,113 cases with positive RNA-HCV genotyping. Detection of infection by age periods was: 0–9 years old – 0.8%, 10–19 – 0.5%, 20–29 – 11%, 30–39 – 32%, 40–49 – 30%, 50–59 – 19.5%, 60–69 – 5.0% and 70–79 – 1.0%. 603 (54.2%) infected people belonged to genotype 1; 107 (9.6%) belonged to genotype 2; 403 (36.2%) belonged to genotype 3. Women were more frequently infected by genotype 1b, with increased percentage of 1ab; men often had genotype 3. 1,513 inhabitants of Dniprо and Dnipropetrovs’k region were sent to be tested for anti-HCV in 2011–2015. The percentage of positive anti-HCV showed a sharp increase from 28% to 64% over the observation period. Detection of HCV by age periods was: 0–9 years old – 0.9%, 10–19 – 1.5%, 20–29 – 9.5%, 30–39 – 27.6%, 40–49 – 27.8%, 50–59 – 23.2%, 60–69 – 8.8% and 70–79 – 0.7%. 1 genotype was identified in 262 (56.8%) infected patients among 461 HCV-infected, 38 (8.2%) had genotype 2, 61 (35%) had genotype 3. 2.6% were diagnosed 1ab. In both populations that were tested, the frequency of detection of HCV was similar among men and women. Gender differences in the spread of genotype 2 haven’t been identified. The disease HCV remains one of the urgent problems of public health in Ukraine.

In a recent expert meeting, Swedish recommendations for the treatment of hepatitis C virus (HCV) infection were updated. An interferon-free combination of direct-acting antiviral agents is considered and indicated for all patients with chronic HCV infection, but the ability to treat all is limited primarily by high cost of medication. The group of patients prioritized for therapeutic intervention has been extended to also include fertile women desiring to become pregnant. A more thorough discussion of treatment for people who inject drugs (PWIDs) in order to diminish transmission is included, and the clinical significance of baseline NS5A resistance associated variants (RAVs), also known as resistance associated substitutions (RASs), for the treatment of HCV genotype 1a or 3 infection is discussed.

Background & Aims: We investigated the efficacy and safety of simeprevir plus daclatasvir in treatment-naïve patients with chronic, genotype 1b hepatitis C virus infection and advanced liver disease, excluding patients with pre-defined NS5A resistance-associated substitutions. Methods: This phase II, open-label, single-arm, multicentre study included patients aged≥18years with advanced fibrosis or compensated cirrhosis (METAVIR F3/4). Patients with NS5A-Y93H or L31M/V resistance-associated substitutions at screening were excluded. Simeprevir (150mg)+daclatasvir (60mg) once daily was administered for 12 or 24weeks; treatment could be extended to 24 weeks prior to or at the Week 12 visit. Primary efficacy endpoint was sustained virological response 12weeks after the end of treatment. Results: A total of 106 patients were treated; 27% patients were aged >65years, 39% had cirrhosis, 53% had estimated glomerular filtration rate 30-89mL/min, 14% had diabetes, and 38% had arterial hypertension. Overall, 42/106 received 12weeks of treatment and 64/106 received 24weeks of treatment. Ninety-seven (92%) patients achieved a sustained virological response 12 weeks after the end of treatment. The reasons for failure were viral breakthrough (n=7) at weeks 4-16, early treatment discontinuation (n=1) and viral relapse (n=1). Seventy-four (70%) patients had ≥1 adverse event during treatment, including six (6%) patients with ≥1 serious adverse event. Three (3%) patients discontinued treatment owing to adverse events. Conclusions: Simeprevir+daclatasvir demonstrated strong antiviral activity and was well-tolerated in patients with hepatitis C virus genotype 1b infection, advanced liver disease and a high prevalence of comorbidities. However, viral breakthrough occurred in seven patients, making this regimen unsatisfactory.

Objectives and design:Hepatitis C virus (HCV) has been recognized as an emerging sexually transmitted infection (STI) among HIV-positive MSM. However, HIV-negative MSM at high risk for HIV might also be at increased risk for HCV. We studied the HCV prevalence in HIV-negative MSM who start preexposure prophylaxis (PrEP) in Amsterdam. Phylogenetic analysis was used to compare HCV strains obtained from HIV-negative and HIV-positive MSM.Methods:At enrolment in the Amsterdam PrEP demonstration project, HIV-negative MSM were tested for the presence of HCV antibodies and HCV RNA. If positive for HCV RNA, an HCV NS5B gene fragment (709bp) was sequenced and compared with HCV isolates from HIV-positive MSM (n=223) and risk groups other than MSM (n=153), using phylogenetic analysis.Results:Of 375 HIV-negative MSM enrolled in Amsterdam PrEP, 18 (4.8%, 95% confidence interval 2.9-7.5%) of participants were anti-HCV and/or HCV RNA positive at enrolment; 15 of 18 (83%) had detectable HCV RNA. HCV genotyping showed genotype 1a (73%), 4d (20%), and 2b (7%). All HCV-positive MSM starting PrEP were part of MSM-specific HCV clusters containing MSM with and without HIV.Conclusion:HCV prevalence among HIV-negative MSM who started PrEP was higher than previously reported. All HIV-negative HCV-positive MSM were infected with HCV strains already circulating among HIV-positive MSM. The increasing overlap between sexual networks of HIV-positive and HIV-negative MSM might result in an expanding HCV-epidemic irrespective of HIV-status. Hence, routine HCV testing should be offered to MSM at high risk for HIV, especially for those enrolling in PrEP programs. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved

Background Hepatitis C (HCV) NS5A resistance associated amino-acid substitutions (RAS) can exist at baseline in treatment naive individuals and have been shown to be associated with lower rates of sustained virological response (SVR) for patients infected with HCV genotype 1A (G1A) following treatment with NS5A inhibitors. Objectives The aim of this study was to measure the prevalence of baseline NS5A resistance in Scotland. Study design The study population consisted of 531 treatment naive, G1A infected patients. The patient samples were collected between March and September 2017. The NS5A region was amplified and sequenced. Results Baseline NS5A resistance in Scotland is high (16.8%) and is comparable to rates reported by a number of previously published studies. The high rate of baseline RAS, together with the high cost of direct-acting antivirals (DAAs), supports resistance testing to guide current patient treatment. However, given the rate at which new DAAs are currently being licensed with ever broader genotype efficacy and higher SVR rates, baseline resistance testing may not be required in the near future. Conclusions Baseline NS5A inhibitor resistance is high. The results of the present study support performing resistance testing at baseline for current regimens.

Background and Aim. The development of interferon- (IFN-) free regimens substantially improved efficacy of treatment for HCV, but despite excellent effectiveness the failures still occur. The aim of our study was to evaluate the efficacy of retreatment with genotype specific direct acting antivirals- (DAA-) based regimens in nonresponders to previous IFN-free therapy. Materials and Methods. Analysed population consisted of 31 nonresponders to IFN-free regimen, which received second IFN-free rescue therapy, selected from 6228 patients included in a national database EpiTer-2. Results. Age and gender distribution were similar, whereas proportion of genotype 1b was slightly higher and genotype 4 lower in the whole population compared to studied one. Patients included in the study demonstrated much more advanced fibrosis. Primary therapy was discontinued in 12 patients, which were recognized as failures due to nonvirologic reason, whereas virologic reason of therapeutic failure was recognized in 19 patients which completed therapy. Overall sustained virologic response (SVR) rate was 81% and 86% in intent-to-treat (ITT) and modified ITT analysis, respectively (74% and 78% in virologic failures, 92% and 100% in nonvirologic failures). Resistance-associated substitutions (RAS) testing was carried out in 8 patients from the group of completed primary therapy and three of them had potential risk for failure of rescue therapy due to NS5A association, while two of them achieved SVR. Conclusions. We demonstrated moderate effectiveness of genotype specific rescue therapy in failures due to virologic reason and high in those who discontinued primary therapy. Therefore rescue therapy with genotype specific regimens should be considered always if more potent regimens are not available.

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain-1 interacts with cellular proteins inducing pro-oncogenic pathways. Thus, we explore genetic variations in NS5A domain-1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype-1b infected DAA-naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p &lt, 0.001), M133I (20.6% vs. 3.9%, p &lt, 0.001), and Q181E (11.8% vs. 0.6%, p &lt, 0.001). By multivariable analysis, the presence of &gt, 1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3), p &lt, 0.001). Focusing on HCC-group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell-cycle regulation (p53, p85-PIK3, and β-catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV-mediated oncogenesis. The role of theseNS5A domain-1 mutations in triggering pro-oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation.

Background & Aims Hepatitis C viral infection (HCV) after injection drug use is very prevalent. The kind of genotype determines the response to treatment. However, no systematic review update on the global genotype distribution of HCV in people who inject drugs (PWID) is currently available. Methods A systematic review was performed by using the keywords: Genotype, Hepatitis C, Injection drug user/Intravenous drug user/Substance user/ PWID, Name of countries in Pubmed, Embase and PsycINFO. The results were compared with the review of Gower et al. in 2014, concerning the distribution of HCV genotypes in the general HCV population. Results Using these keywords, 132 studies in 48 countries (from 1995 to 2015) were collected. After grading these results, the data of 48 studies were used to determine the distribution of genotypes in PWID. Genotype 1 is the most prevalent genotype all over the world in PWID. In Europe, genotypes 1, 3 and 4 are highly prevalent. In North and South America and in Australia genotype 1 and 3 are most prevalent. In Asia genotype 2 and 6, and Africa genotype 1a and 4 are mostly observed. Overall, the most important differences comparing with the general population are a lower prevalence of genotype 1b in the PWID population and higher prevalence of genotype 1a and 3. Conclusions There is a different prevalence of genotype distribution in PWID than in the general population. Genotype 3 is especially highly prevalent in the Western countries. Lay summary Hepatitis C viral infection after injection drug use is very prevalent. The most important genotype causing HCV infection in PWID globally is genotype 1, as is the case in the general population, but also genotype 3 is highly prevalent in PWID. Genotype 4 is most prevalent in Africa, spreading into Europe, whereas genotype 2 and 6 are more located in Asia. The most important difference comparing to the general population are generally lower prevalence of genotype 1b, and higher prevalence of genotype 1a and 3 in PWID. As the genotype nowadays still determines the treatment, and as there is a different genotype distribution than in the general population, it is important to identify the genotype also in PWID.

A new class of hepatitis C NS3/4A inhibitors was identified by introducing a novel spirocyclic proline–P2 surrogate onto the P2–P4 macrocyclic core of MK-5172 (grazoprevir). The potency profile of new analogues showed excellent pan-genotypic activity for most compounds. The potency evaluation included the most difficult genotype 3a (EC50 values ≤10 nM) and other key genotype 1b mutants. Molecular modeling was used to design new target compounds and rationalize our results. A synthetic approach based on the Julia–Kocienski olefination and macrolactamization to assemble the P2–P4 macrocyclic core containing the novel spirocyclic proline–P2 moiety is presented as well.

Sustained virological responses (SVR) by daclatasvir (DCV) and asunaprevir (ASV) therapy for genotype 1b hepatitis C virus (HCV) infected patients has been significantly affected by pre-existence of Y93 H resistance-associated variants (RAVs) in the non-structural protein 5A (NS5A) region. The aim of this study was to elucidate the dominancy of naturally occurring RAVs in viral quasispecies on treatment outcomes in patients with HCV. In total, 138 patients were prospectively selected from 152 patients treated with DCV and ASV, where evaluation of treatment outcomes at 12 weeks post-treatment was possible. Pre-treatment RAVs in the non-structural protein 3 and NS5A regions were detected by polymerase chain reaction (PCR)-Invader assays, and the ratio of Y93H RAVs in viral quasispecies was measured by quantitative PCR-Invader assay. Among 25 patients detected the Y93H RAV, the Y93H ratio was 1-25% in 5 patients, 26-75% in 7 patients, and ≥76% in 13 patients. Overall, SVR at 12 weeks after the completion of treatment (SVR12) was 91% (125/138), and those with Y93H ratios of

Key Clinical Message There is currently minimal clinical experience regarding retreatment options for patients failing direct‐acting antiviral combination regimens. Here, we report the outcomes of a HCV genotype 1b‐infected patient with virologic failure following treatment with daclatasvir and asunaprevir, who was successfully retreated with sofosbuvir plus simeprevir.

Introduction: Chronic hepatitis C cases diagnosed in Romania were mostly related to unsafe parenteral treatments and blood transfusions; HCV genotype 1b was prevalent. During the last decade, an increasing number of HCV infections was reported among people who inject drugs (PWID). The aim of the current study was to test if this epidemiological shift triggered a diversification of the circulating viral strains. Methodology: HCV genotypes were determined by reverse hybridization in 130 HCV-infected PWID (87.7% males; mean age 27.9 ± 6.7 years, injecting drugs for 8.1 ± 4.8 years). Results: HIV-HCV co-infection was diagnosed in 80.8% of the subjects and 26.9% were HIV-HCV-HBV triple infected. Active HCV viral replication was present in 104 PWID (80%), more frequently in those HIV-co-infected (91.4% vs. 52% in HCV mono-infected, and 77.148.5% in HIV-HCV-HBV triple-infected, p = 0.0001). Non-1b genotypes were prevalent (54.8%), with subtype 1a the most commonly detected (24%), followed by genotypes 3a (14.4%) and 4 (7.7%). Mixed infections with genotypes 1a and 1b were found in nine subjects (8.7%). There was no difference in the genotypes frequencies based on HIV or HBV co-infection status, length of drug usage, or associated risk factors (tattoos, piercing, detention). Conclusion: The continuous surveillance of HCV genotypes in PWID from Romania will add valuable information to the overall European epidemiological picture, with important therapeutic implications.

OZ Objective: It was aimed to investigate diagnostic value of hepatitis C virus (HCV) core antigen test in patients with positive or negative anti-HCV assay by comparing with HCV ribonucleic acid (RNA) assay. Materials and Methods: Serum samples obtained from 189 patients who were admitted to Necmettin Erbakan University Meram Faculty of Medicine between December 2010 and February 2012, and HCV RNA assay were carried out for various reasons. Two mL of samples were stored under suitable conditions and antiHCV, HCV core antigen and strip immunoblot assay [Commercial INNO LIA™ HCV Score (Innogenetics NV in Ghent, Belgium)] were performed. Genotyping was performed in the amplicons of the samples with positive HCV RNA test. Results: The diagnostic sensitivity specificity, negative predictive value and positive predictive value of HCV core antigen test were 96.2%, 100%, 97.3%, and 100%, respectively. Sixty-five serum samples were genotyped and their distribution were detected: Fiftynine samples were genotype 1b, 2-genotype 1a/1b, 1-genotype 3a, 1-genotype 4, 1-genotype 2a/2c, and 1 was genotype 1a. Conclusion: It was concluded that HCV core antigen assay is highly specific, sensitive, reliable, reproducible, and easy to perform. It may be applied as a supplemental and confirmatory test in anti-HCV assays in the diagnosis of HCV.

Background Screening of the natural HCV NS3 polymorphism Q80K is required prior to simeprevir administration due to the reduced susceptibility of genotype 1 viruses carrying this amino acid variant. A simple, rapid and robust test for Q80K screening would be advisable in routine diagnostic laboratories. Objectives The aim of this study was to evaluate a commercial NS3 Q80K real-time PCR kit (Q80K Polymorphism Kit, Clonit srl, Milan, Italy). Study design Forty-three plasma samples obtained from untreated HCV genotype 1a-infected patients and previously sequenced at a reference laboratory, were sent to two public clinical virology laboratories for blinded Q80K screening with the kit under evaluation. The sample panel included 25 cases with the wild type 80Q, 17 with the mutant 80K and 1 with the mutant 80L. Results Laboratory 1 identified 22/25 (88.0%) 80Q and 17/17 (100.0%) 80K cases. Laboratory 2 identified 23/25 (92.0%) 80Q and 16/17 (94.2%) 80K cases. All of the unidentified cases were scored as negative, with no mutant/wild type miscalling. The 80L variant was scored as indeterminate by Laboratory 1 and as negative by Laboratory 2. Overall, sensitivity and specificity for detection of 80K were 97.1% (95% C.I., 82.9–99.8%) and 100.0% (90.2–100.0%), respectively. However, the system did not provide any result for 6/84 cases (7.1% failure rate), not including the 80L variant which is not expected to be detected as stated in the kit package insert. Global inter-laboratory concordance was 93.0%. Conclusions Despite good specificity, this Q80K detection system needs improvements in amplification success rate and robustness.