OBJECTIVES: To follow on the epidemiology of HCV, especially genotypes spreading among people who inject drugs (PWID) in Prague and surrounding Central Bohemia, Czech Republic. METHODS: 546 patients who reported past and/or recent injecting of drugs were recruited in the years 2010-2012. They were initially tested for anti-HCV. Real-time PCR was used for quantification and genotyping of hepatitis C virus. Obtained data from the years 2010-2012 were compared with historical controls from periods of 1998-2000 and 2005-2007. RESULTS: Of 546 initially recruited and tested patients were 393 (72%) anti-HCV seropositive and of them 269 (68.4%) had detectable HCV PCR RNA. The most prevalent subtype was 3a in 97 patients (36.1%), 1a was detected in 85 patients (31.6%) and 1b in 57 patients (21.2%). These three genotypes were responsible for nearly 89% of infections. CONCLUSION: Significant increase in both genotypes 1a and 3a over the 15 years was apparent and significant, followed by the decrease in genotype 1b. In the genotype 1b and genotype 3a the significance has risen with the years of data collection. Described genotypic shift reflects the evolution of HCV epidemics and corresponds with the mode of transmission.

• Klíčová slova
• Czech Republic, HCV, HCV genotypes, people who inject drugs,
• MeSH
• genotyp * MeSH
• Hepacivirus * MeSH
• hepatitida C * epidemiologie   genetika   MeSH
• lidé MeSH
• prevalence MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

Genotyping of hepatitis C virus (HCV) is of relevance to scheduling the treatment of patients with chronic hepatitis C (VHC), making their prognosis and monitoring the treatment efficacy. A set of 62 sera testing HCV RNA positive in Cobas Amplicor HCV 2.0 test (CA) were genotyped using Versant HCV Genotype Assay (LiPA) Bayer, i.e. the reverse hybridization method, with the CA amplified product being directly used in the assay. Fifty-six out of 57 samples reactive in reverse hybridization (92%) were genotyped. One sample showed a profile differing from any genotype, five samples were not reactive and one sample was not tested within this study design. Two out of five non-reactive sera and one non-tested serum could be genotyped by nested PCR based reverse hybridization. It can be concluded that the CA product resulting from one-step HCV RNA amplification is suitable for use in genotyping by reverse hybridization. The CA product based genotyping procedure is easier to perform, less time-consuming and less costly. The nested PCR based procedure could be used for typing of sera with lower HCV concentrations nontypeable with the combination of CA and Versant HCV Genotype Assay. Forty-eight selected samples were typed not only by reverse hybridization but also by a serological kit Murex HCV Serotyping 1-6 Assay (Abbot Murex). Thirty-seven (77%) of these sera, including all of three sera negative in reverse hybridization, appeared typeable by this kit. Although less sensitive, serotyping may be of relevance to typing of sera with low HCV levels or not containing detectable viral NA which are nontypeable by reverse hybridization. Thirty-three sera appeared genotypeable by both of the methods tested with the results being in good agreement. In two cases only the serotyping method revealed one more type of virus (mixed genotype) compared to the reverse hybridization.

• MeSH
• chronická hepatitida C virologie   MeSH
• genotyp MeSH
• Hepacivirus klasifikace   genetika   MeSH
• hybridizace nukleových kyselin MeSH
• lidé MeSH
• polymerázová řetězová reakce MeSH
• RNA virová analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• RNA virová MeSH

BACKGROUND & AIMS: Eight-week glecaprevir/pibrentasvir leads to high rates of sustained virological response at post-treatment week 12 (SVR12) across HCV genotypes (GT) 1-6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis. METHODS: EXPEDITION-8 was a single-arm, multicenter, phase IIIb trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% CI of the SVR12 rate in i) patients with GT1,2,4-6 in the per protocol (PP) population, ii) patients with GT1,2,4-6 in the intention-to-treat (ITT) population, iii) patients with GT1-6 in the PP population, and iv) patients with GT1-6 in the ITT population, to pre-defined efficacy thresholds based on historical SVR12 rates for 12 weeks of glecaprevir/pibrentasvir in the same populations. Safety was also assessed. RESULTS: A total of 343 patients were enrolled. Most patients were male (63%), white (83%), and had GT1 (67%). The SVR12 rate in patients with GT1-6 was 99.7% (n/N = 334/335; 95%CI 98.3-99.9) in the PP population and 97.7% (n/N = 335/343; 95% CI 96.1-99.3) in the ITT population. All primary and key secondary efficacy analyses were achieved. One patient (GT3a) experienced relapse (0.3%) at post-treatment week 4. Common adverse events (≥5%) were fatigue (9%), pruritus (8%), headache (8%), and nausea (6%). Serious adverse events (none related) occurred in 2% of patients. No adverse event led to study drug discontinuation. Clinically significant laboratory abnormalities were infrequent. CONCLUSIONS: Eight-week glecaprevir/pibrentasvir was well tolerated and led to a similarly high SVR12 rate as the 12-week regimen in treatment-naïve patients with chronic HCV GT1-6 infection and compensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03089944. LAY SUMMARY: This study was the first to evaluate an 8-week direct-acting antiviral (DAA) regimen active against all major types of hepatitis C virus (HCV) in untreated patients with compensated cirrhosis. High virological cure rates were achieved with glecaprevir/pibrentasvir across HCV genotypes 1-6, and these high cure rates did not depend on any patient or viral characteristics present before treatment. This may simplify care and allow non-specialist healthcare professionals to treat these patients, contributing to global efforts to eliminate HCV.

• Klíčová slova
• Chronic HCV infection, Compensated cirrhosis, Direct-acting antiviral, Glecaprevir/pibrentasvir, HCV elimination, Hepatitis C virus, Pangenotypic, Short duration,
• MeSH
• antivirové látky aplikace a dávkování   škodlivé účinky   MeSH
• benzimidazoly aplikace a dávkování   škodlivé účinky   MeSH
• chinoxaliny aplikace a dávkování   škodlivé účinky   MeSH
• chronická hepatitida C krev   komplikace   farmakoterapie   virologie   MeSH
• cyklopropany aplikace a dávkování   škodlivé účinky   MeSH
• fixní kombinace léků MeSH
• genotyp * MeSH
• Hepacivirus enzymologie   genetika   MeSH
• jaterní cirhóza komplikace   farmakoterapie   MeSH
• kyseliny aminoisomáselné aplikace a dávkování   škodlivé účinky   MeSH
• leucin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrocyklické laktamy aplikace a dávkování   škodlivé účinky   MeSH
• polymorfismus genetický MeSH
• prolin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• pyrrolidiny aplikace a dávkování   škodlivé účinky   MeSH
• RNA virová krev   genetika   MeSH
• senioři MeSH
• setrvalá virologická odpověď MeSH
• sulfonamidy aplikace a dávkování   škodlivé účinky   MeSH
• virové nestrukturální proteiny genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antivirové látky MeSH
• benzimidazoly MeSH
• chinoxaliny MeSH
• cyklopropany MeSH
• fixní kombinace léků MeSH
• glecaprevir MeSH Prohlížeč
• kyseliny aminoisomáselné MeSH
• leucin MeSH
• makrocyklické laktamy MeSH
• NS-5 protein, hepatitis C virus MeSH Prohlížeč
• NS3 protein, hepatitis C virus MeSH Prohlížeč
• pibrentasvir MeSH Prohlížeč
• prolin MeSH
• pyrrolidiny MeSH
• RNA virová MeSH
• sulfonamidy MeSH
• virové nestrukturální proteiny MeSH

STUDY OBJECTIVES: Analysis of the genotypic distribution of HCV from blood donors screened in the Czech Republic in 1999-2007 and sequence heterogeneity of HCV isolates in the NS5 region of the HCV genome. MATERIAL AND METHODS: A total of 402 archived serum samples from blood donors collected in 1999-2007 and confirmed positive for anti-HCV antibodies were tested for HCV RNA. In 220 HCV RNA positive sera, PCR was used to amplify a 401-nt fragment of the NS5 region of the HCV genome. The PCR product was sequenced and phylogenetic analysis of the obtained nucleotide sequences was carried out. Genotyping was performed based on the comparison with the sequence data available in the Genbank database. Regression analysis and non-parametric Pearson's chi-square test were used for statistical analysis of the distribution of genotypes by age, sex, sampling place and sampling year. RESULTS: In a representative set of 188 blood donors from the Czech Republic, the following HCV genotypes were determined: 1b (66%), 1a (13.3%), 3 (19.7%), 2a (0.5%) and 2b (0.5%). In 1999-2007, genotype 1b showed a significantly decreasing trend while genotype 3a was becoming significantly more frequent and the incidence of genotype 1a remained unchanged. It was found that the proportion of genotype 1b rises with increasing age of blood donors in contrast to genotypes 1a a 3a. Genotype 1b was detected significantly more frequently in females and genotype 3a significantly predominated in males. Any significant difference was not found in the geographical distribution of HCV genotypes. The mean HCV viral load was 9.6 x 105 I.U./ml. CONCLUSIONS: The predominant HCV genotype among blood donors in the Czech Republic is 1b, showing a significant downward trend in 1999-2007. The increasing prevalence of genotype 3a can be associated with changes in the route of HCV transmission, more precisely with the considerably increased incidence of HCV in injecting drug users over the last 15 years. Surprisingly, the incidence of genotype la remained unchanged over the study period.

• MeSH
• dárci krve * MeSH
• dospělí MeSH
• genotyp MeSH
• Hepacivirus klasifikace   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• sekvenční analýza RNA MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

OBJECTIVE: Hepatitis C virus (HCV) genotyping is an important part of pre-treatment diagnostic algorithms as it guides the choice of therapeutic regimens. The aim of this study was to analyse the distribution of HCV genotypes in patients with chronic hepatitis C from Croatia in the period 2008-2015. METHODS: The study enrolled 3,655 anti-HCV positive patients with available results of HCV genotyping from the three largest national HCV genotyping laboratories. RESULTS: The majority of HCV-infected individuals enrolled in the study were male (70.7%). Analysis of age distribution in a subset of 2,164 individuals showed a mean age of 40.9 years (SD 11.77 years). Croatian patients were mostly infected with HCV genotype 1 (56.6%), followed by genotype 3 (37.3%), genotype 4 (4.2%) and genotype 2 (1.8%). Genotype 1 subtyping in a subset of 1,488 patients showed 54% (803/1,488) of 1b infections and 46% (685/1,488) of 1a infections. Percentages of genotype 1 were the highest in Central/Northwestern and Eastern Croatia and the lowest in the Central/Southern Adriatic Region. Genotype 3 was most frequently found in the Central/Southern Adriatic Region (49.1%) but represented only 17.5% of infections in Eastern Croatia (p < 0.001). CONCLUSIONS: The results of this nine-year retrospective analysis on the distribution of HCV genotypes and subtypes in 3,655 HCV-infected individuals from Croatia showed that the majority of infections can be attributed to genotypes 1 and 3 with absence of major changes in the molecular epidemiology of the two most frequent HCV genotypes infection in Croatia in the past 20 years.

• Klíčová slova
• Croatia, genotypes, hepatitis C virus, subtypes,
• MeSH
• chronická hepatitida C epidemiologie   virologie   MeSH
• dospělí MeSH
• genotyp MeSH
• Hepacivirus genetika   MeSH
• lidé MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Chorvatsko epidemiologie   MeSH

New therapeutic options became available in 2015 in the European Union. We present the availability of interferon-free regimens with direct acting antivirals (DAA) in four Central European countries - the Czech Republic, Hungary, Poland and Slovakia - which despite similar historical, geographical and economic situations demonstrate different systems for access to anti-HCV (hepatitis C virus) medication. Treatment of patients in the Czech Republic was based in 2015 on an exceptional individual reimbursement procedure, but regular reimbursement procedures are expected in 2016. In Hungary the decision for treatment is balanced against budget limitations and the national Priority Index system reflecting stage of liver disease, activity of the disease and predictive factors. A reimbursed interferon (IFN)-free therapeutic program for all genotypes, without restrictions related to hepatic fibrosis and treatment history, is already available in Poland. In Slovakia patients with advanced fibrosis are currently selected for possible IFN-free therapy in 2016.

• Klíčová slova
• Central Europe, HCV, treatment,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Little is known about the distribution of hepatitis C virus (HCV) genotypes among people who inject drugs (PWID) in North African countries, including Tunisia. This study aims to describe HCV genotypes circulating among Tunisian PWID. A cross-sectional study was conducted, and 128 HCV-positive PWID were recruited between 2018 and 2019 from community-based harm reduction centers. After informed consent, sociodemographic characteristics and risk behavior data were obtained using an interviewer-administrated questionnaire. Blood samples were collected for further serological and molecular testing. Overall, five women and 123 men were included. The median age was 39.5 years. The majority of PWID (56.3%) had less than a secondary level of education, were single (57%), were unemployed (65.6%), were incarcerated at least once (93.0%), and had a history of residency in at least one foreign country (50.8%). During the previous 12 months, 82.0% reported having reused syringes at least once, 43.8% shared syringes at least once, while 56.2% had at least one unprotected sexual relation, and 28.1% had more than two different sexual partners. Tattooing was reported among 60.2%. All positive results for HCV-infection by rapid testing were confirmed by enzyme-linked immunosorbent assay (ELISA). HCV-RNA was detectable in 79.7%. Genotyping showed a predominance of genotype 1 (52%) followed by genotype 3 (34%) and genotype 4 (10%). Four patients (4%) had an intergenotype mixed infection. Subtyping showed the presence of six different HCV subtypes as follows: 1a (53.2%), 1b (6.4%), 3a (33.0%), 4a (3.2%), and 4d (4.3%). This is the first study describing circulating HCV genotypes among PWID in Tunisia. The distribution of HCV genotypes is distinct from the general population with a predominance of subtypes 1a and 3a. These findings can be used to guide national efforts aiming to optimize the access of PWID to relevant HCV prevention and treatment measures including pangenotypic regimens for patients infected with HCV genotype 3.

• Klíčová slova
• PWID, Tunisia, hepatitis C virus, injecting drug users, prevention, substance abuse, treatment,
• Publikační typ
• časopisecké články MeSH

Prevalence of HGV(GBV-C) infection and its coinfection with HBV a HCV infections were studied in group of 82 haemodialysis patients. This study was realized 20 months latter again -- 16 patients from 82 were running in dialysis, 17 patients were transplanted and 49 patients died (non of this viruses was cause of their death). HGV(GBV-C) RNA was detected in serum of 22 patients, 20 months latter it was detected in serum of 3 patients; one positive was new. 20 months latter any HGV(GBV-C) RNA was not detected in serum of 4 originally positive patients. Three of ten HBsAg positive patients were coinfected by HGV(GBV-C) RNA; 20 months latter any coinfection was found. In the first we found HGV(GBV-C) RNA in serum of 5 anti-HCV positive patients and in serum of 1 HCV RNA positive patient; 20 months latter it was in serum of 1 and 1 respectively. Elevation of ALT and AST levels were found in serum of 3 from 82 patients; two patients were coinfected with HBV or HCV. Any from 2 running dialysis patients with elevation of ALT and AST levels was not HGV(GBV-C) RNA positive. This virus is not probably frequent cause of liver disease in dialysis patients and it is not necessary to routinely screen for HGV(GBV-C) infection in this group of patients.

• MeSH
• dialýza ledvin * MeSH
• dospělí MeSH
• hepatitida B komplikace   diagnóza   MeSH
• hepatitida C komplikace   diagnóza   MeSH
• infekce viry z čeledi Flaviviridae komplikace   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• RNA virová analýza   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sérologické testy MeSH
• virová hepatitida u lidí komplikace   diagnóza   MeSH
• virus GB-C * izolace a purifikace   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• RNA virová MeSH

THE AIM OF THE STUDY: To evaluate the efficacy of combined antiviral treatment with pegylated interferon alpha plus ribavirin in patients with chronic HCV infection who have not yet been treated with antivirals (treatment-naive patients). To compare the treatment effect in patients with low (< 600,000 IU/ml) and high (> or = 600,000 IU/ml) initial viremia. METHODS AND TREATMENT REGIME: Treatment-naive patients with chronic HCV infection treated with the combination therapy of pegylated interferon-alpha2a plus ribavirin. Treatment response was evaluated at weeks 12, 24 and 48 when treatment was ongoing and at weeks 12, 24 and 48 after the treatment was finished. Commercially available sets from various manufacturers were used for serum and molecular genetic diagnostics of HCV infection. PATIENT SAMPLE: Antiviral treatment was initiated in 175 patients between 2001 and 2007. The complete data sets suitable for statistical analysis were available for 143 patients. End of treatment response and sustained viral response analyses were conducted separately for HCV genotype 1 (n = 124) and genotype 2 + 3 (n = 7). RESULTS: In the genotype 1 group, 76% of patients achieved end of treatment response and 59% of patients achieved sustained viral response. Both types of response were observed in 100% of the genotype 2 and 3 infected patients. When a correlation between initial viremia and sustained viral response was analysed, no statistically significant difference was observed between patients with low (< 600,000 IU/ml) and high (> or = 600,000 IU/ml) initial viremia. CONCLUSION: The results observed in the present study are generally slightly better than comparable results from large registration studies. In contrary to the published literature, the threshold of 600,000 IU/ml for initial viremia did not correlate statistically significantly with SVR.

• MeSH
• antivirové látky aplikace a dávkování   MeSH
• chronická hepatitida C farmakoterapie   virologie   MeSH
• dospělí MeSH
• genotyp MeSH
• Hepacivirus genetika   MeSH
• interferon alfa-2 MeSH
• interferon alfa aplikace a dávkování   MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• polyethylenglykoly aplikace a dávkování   MeSH
• rekombinantní proteiny MeSH
• ribavirin aplikace a dávkování   MeSH
• viremie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky MeSH
• interferon alfa-2 MeSH
• interferon alfa MeSH
• peginterferon alfa-2a MeSH Prohlížeč
• polyethylenglykoly MeSH
• rekombinantní proteiny MeSH
• ribavirin MeSH

OBJECTIVES: The aim was to introduce a diagnostic method for detecting variants of hepatitis C virus (HCV) with protease NS3 resistance primarily to simeprevir (Q80K mutation in HCV genotype 1a) and its subsequent use in routine practice. MATERIAL AND METHODS: The detection of HCV resistance-associated variants in the NS3 protease gene by sequence analysis was introduced in the molecular biology laboratory of University Hospital Hradec Kralove in 2015. The primers were designed by sequence analysis software Custom Primers - OligoPerfect™ Designer. The method was optimized for HCV genotype 1a. The search for variants was performed using two programs. RESULTS: A total of 16 patients with genotype 1a chronic hepatitis C have been examined since 2015. In five of them, the Q80K variant was detected. CONCLUSION: The development of resistance to antiviral therapy for chronic hepatitis C gained importance after the introduction of direct-acting antivirals. Given the relatively high prevalence of the Q80K mutation in HCV genotype 1a, it is crucial to confirm its presence or absence before the therapy is initiated. The reported method enables clear and early detection of the Q80K mutation.

• MeSH
• Hepacivirus genetika   MeSH
• hepatitida C diagnóza   virologie   MeSH
• lidé MeSH
• mutace genetika   MeSH
• virologie metody   MeSH
• virová léková rezistence genetika   MeSH
• virové nestrukturální proteiny genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• NS3 protein, hepatitis C virus MeSH Prohlížeč
• virové nestrukturální proteiny MeSH