Distribution and molecular characterization of hepatitis C virus (HCV) genotypes in patients with chronic infection from Pernambuco State, Brazil

Hepatitis C virus (HCV) is a public health problem throughout the world and 3% of the world population is infected with this virus. It is estimated that 3-4 millions individuals are being infected every year. It has been estimated that around 1.5% of Brazilian population is anti-HCV positive and the Northeast region showed the highest prevalence in Brazil. The aim of this study was to characterize HCV genotypes circulating in Pernambuco State (PE), Brazil, located in the Northeast region of the country. This study included 85 anti-HCV positive patients followed up between 2004 and 2011. For genotyping, a 380bp fragment of HCV RNA in the NS5B region was amplified by nested PCR. Phylogenetic analysis was conducted using Bayesian Markov chain Monte Carlo simulation (MCMC) using BEAST v.1.5.3. From 85 samples, 63 (74.1%) positive to NS5B fragment were successfully sequenced. Subtype 1b was the most prevalent in this population (42-66.7%), followed by 3a (16-25.4%), 1a (4-6.3%) and 2b (1-1.6%). Twelve (63.1%) and seven (36.9%) patients with HCV and schistosomiasis were infected with subtypes 1b and 3a, respectively. Brazil is a large country with many different population backgrounds; a large variation in the frequencies of HCV genotypes is predictable throughout its territory. This study reports HCV genotypes from Pernambuco State where subtype 1b was found to be the most prevalent. Phylogenetic analysis suggests the presence of the different HCV strains circulating within this population. (C) 2012 Elsevier B.V. All rights reserved.

Sesquiterpene Lactones with Anti-Hepatitis C Virus Activity Using Molecular Descriptors

Hepatitis C is a worldwide public health problem. The available therapies are limited by their partial effectiveness and with meaningful side-effects. Sesquiterpene lactones (SLs) are a group of natural products with a wide variety of chemical structures and biological activities associated. There are few studies about the influence of the molecular structure of SLs for the anti-hepatitis C virus activity. In the present work, SLs are investigated in a subgenomic RNA replicon assay system and were analyzed using multiple linear regression along with self-organizing maps with DRAGON descriptors in order to identify the structural requirements for their biological activity and to predict the inhibitory potency of SLs. Characteristics such as stereochemistry and electronic effects demonstrated to be important for their anti-HCV activity, and the SOM produced a clear separation betwenn active and inactive compounds. Therefore, it is possible to use this map as a filter for virtual screening to predict the anti-HCV activity of SLs.

Distribution of hepatitis c virus (hcv) genotypes in patients with chronic infection from Rondônia, Brazil

Abstract Background Hepatitis C virus (HCV) is an important human pathogen affecting around 3% of the human population. In Brazil, it is estimated that there are approximately 2 to 3 million HCV chronic carriers. There are few reports of HCV prevalence in Rondônia State (RO), but it was estimated in 9.7% from 1999 to 2005. The aim of this study was to characterize HCV genotypes in 58 chronic HCV infected patients from Porto Velho, Rondônia (RO), Brazil. Methods A fragment of 380 bp of NS5B region was amplified by nested PCR for genotyping analysis. Viral sequences were characterized by phylogenetic analysis using reference sequences obtained from the GenBank (n = 173). Sequences were aligned using Muscle software and edited in the SE-AL software. Phylogenetic analyses were conducted using Bayesian Markov chain Monte Carlo simulation (MCMC) to obtain the MCC tree using BEAST v.1.5.3. Results From 58 anti-HCV positive samples, 22 were positive to the NS5B fragment and successfully sequenced. Genotype 1b was the most prevalent in this population (50%), followed by 1a (27.2%), 2b (13.6%) and 3a (9.0%). Conclusions This study is the first report of HCV genotypes from Rondônia State and subtype 1b was found to be the most prevalent. This subtype is mostly found among people who have a previous history of blood transfusion but more detailed studies with a larger number of patients are necessary to understand the HCV dynamics in the population of Rondônia State, Brazil.

Transforming growth factor alpha immunoreactivity. A study in hepatocellular carcinoma and in non-neoplastic liver tissue

Background. Transforming growth factor alpha (TGF alpha) is an important mitogen that binds to epidermal growth factor receptor and is associated with the development of several tumors. Aims. Assessment of the immunoexpression of TGF alpha in hepatocellular carcinoma (HCC) and in non-neoplastic liver tissue and its relationship to morphological patterns of HCC. Material and methods. The immunohistochemical expression of TGF alpha was studied in 47 cases of HCC (27 multinodular, 20 nodular lesions). Five lesions measured up to 5 cm and 15 lesions above 5 cm. Thirty-two cases were graded as I or II and 15 as III or IV. The non-neoplastic tissue was examined in 40 cases, of which 22 had cirrhosis. HBsAg and anti-HCV were positive in 5/38 and 15/37 patients, respectively. The statistical analysis for possible association of immunostaining of TGF alpha and pathological features was performed through chi-square test. Results. TGF alpha was detected in 31.9% of the HCC and in 42.5% of the non-neoplastic. There was a statistically significant association between the expression of TGF alpha and cirrhosis (OR = 8.75, 95% CI = [1.93, 39.75]). The TGF alpha was detected more frequently in patients anti-HCV(+) than in those HBsAg(+). The immunoexpression of TGF alpha was not found related to tumor size or differentiation. In conclusion the TGF alpha is present in hepatocarcinogenesis in HBV negative patients. Further analysis is needed to examine the involvement of TGF alpha in the carcinogenesis associated with HCV and other possible agents. In addition, TGF alpha has an higher expression in hepatocyte regeneration and proliferation in cirrhotic livers than in HCC.

Risk factors for hepatitis C virus infection in Inland Brazil: An analysis of pooled epidemiological sectional studies

In order to assess the contribution of different parenteral routes as risk exposure to the hepatitis C virus (HCV), samples from nine surveys or cross-sectional studies conducted in two Brazilian inland regions were pooled, including a total of 3,910 subjects. Heterogeneity among the study results for different risk factors was tested and the results were shown to be homogeneous. Anti-HCV antibodies were observed in 241 individuals, of which 146 (3.7%, 95% CI?=?3.24.4) had HCV exposure confirmed by immunoblot analysis or PCR test. After adjustment for relevant variables, a correlation between confirmed HCV exposure and injection drug use, tattooing, and advance age was observed. In a second logistic model that included exposures not searched in all nine studies, a smaller sample was analyzed, revealing an independent HCV association with past history of surgery and males who have sex with other males, in addition to repeated injection drug use. Overall, these analyses corroborate the finding that injection drug use is the main risk factor for HCV exposure and spread, in addition to other parenteral routes. J. Med. Virol. 84:756762, 2012. (C) 2012 Wiley Periodicals, Inc.

Acute hepatitis C virus infection assessment among chronic hemodialysis patients in the Southwest Parana State, Brazil

Abstract Background Chronic hemodialysis patients are at higher risk for acquiring hepatitis C virus (HCV). The prevalence varies among different countries and hemodialysis centers. Although guidelines for a comprehensive infection control program exist, the nosocomial transmission still accounts for the new cases of infection. The aim of this study was analyze the follow up of newly acquired acute hepatitis C cases, during the period from January 2002 to May 2005, in the Hemodialysis Center, located in the Southwest region of Parana State, Brazil and to analyze the effectiveness of the measures to restrain the appearance of new cases of acute hepatitis C. Methods Patients were analyzed monthly with anti-HCV tests and ALT measurements. Patients with ALT elevations were monitored for possible acute hepatitis C. Results During this period, 32 new cases were identified with acute hepatitis C virus infection. Blood screening showed variable ALT levels preceding the anti-HCV seroconversion. HCV RNA viremia by PCR analysis was intermittently and even negative in some cases. Ten out of 32 patients received 1 mcg/kg dose of pegylated interferon alfa-2b treatment for 24 weeks. All dialysis personnel were re-trained to strictly follow the regulations and recommendations regarding infection control, proper methods to clean and disinfect equipment were reviewed and HCV-positive patients were isolated. Conclusion Laboratory tests results showed variable ALT preceding anti-HCV seroconversion and intermittent viremia. The applied recommendations contributed importantly to restrain the appearance of new cases of acute hepatitis C in this center and the last case was diagnosed in May 2004.

Prevalence and risk factors of Hepatitis C virus infection in Brazil, 2005 through 2009: a cross-sectional study

Abstract Background Hepatitis C chronic liver disease is a major cause of liver transplant in developed countries. This article reports the first nationwide population-based survey conducted to estimate the seroprevalence of HCV antibodies and associated risk factors in the urban population of Brazil. Methods The cross sectional study was conducted in all Brazilian macro-regions from 2005 to 2009, as a stratified multistage cluster sample of 19,503 inhabitants aged between 10 and 69 years, representing individuals living in all 26 State capitals and the Federal District. Hepatitis C antibodies were detected by a third-generation enzyme immunoassay. Seropositive individuals were retested by Polymerase Chain Reaction and genotyped. Adjusted prevalence was estimated by macro-regions. Potential risk factors associated with HCV infection were assessed by calculating the crude and adjusted odds ratios, 95% confidence intervals (95% CI) and p values. Population attributable risk was estimated for multiple factors using a case–control approach. Results The overall weighted prevalence of hepatitis C antibodies was 1.38% (95% CI: 1.12%–1.64%). Prevalence of infection increased in older groups but was similar for both sexes. The multivariate model showed the following to be predictors of HCV infection: age, injected drug use (OR = 6.65), sniffed drug use (OR = 2.59), hospitalization (OR = 1.90), groups socially deprived by the lack of sewage disposal (OR = 2.53), and injection with glass syringe (OR = 1.52, with a borderline p value). The genotypes 1 (subtypes 1a, 1b), 2b and 3a were identified. The estimated population attributable risk for the ensemble of risk factors was 40%. Approximately 1.3 million individuals would be expected to be anti-HCV-positive in the country. Conclusions The large estimated absolute numbers of infected individuals reveals the burden of the disease in the near future, giving rise to costs for the health care system and society at large. The known risk factors explain less than 50% of the infected cases, limiting the prevention strategies. Our findings regarding risk behaviors associated with HCV infection showed that there is still room for improving strategies for reducing transmission among drug users and nosocomial infection, as well as a need for specific prevention and control strategies targeting individuals living in poverty.