Circulation of HDV Genotypes in Brazil: Identification of a Putative Novel HDV-8 Subgenotype.

Hepatitis D virus (HDV) is classified into 8 genotypes (1 to 8) and several subgenotypes. In Brazil, HDV-3 and HDV-1 predominate; however, most of the diagnosis efforts and molecular studies are directed to the area of endemicity of the Amazon Basin. Here, we determined the molecular epidemiological profile of circulating HDV in Brazilian HBsAg-positive patients between 2013 and 2015 in areas of endemicity and non-areas of endemicity. From 38 anti-HDV-positive individuals, 13 (34.2%) had detectable HDV-RNA and 11 (28.9%) were successfully sequenced. Partial HDAg (~320 nt) sequencing followed by phylogenetic analysis with reference sequences resulted in the identification of HDV-3 (9/11; 81.8%), HDV-5 (1/11; 9.1%), and HDV-8 (1/11; 9.1%). Most HDV-3 samples (8/9; 88.9%) were found in the endemic North region, while one was found in Central-West Brazil, a non-area of endemicity. HDV-5 and 8, genotypes native from African countries, were found in São Paulo, a cosmopolitan city from Southeast Brazil with a high circulation of immigrants. Phylogenetic analysis of HDV-8 strains indicated that the sample determined in our study, along with previously reported sequences from Brazil, formed a highly supported monophyletic clade, likely representing a putative novel HDV-8 subgenotype. IMPORTANCE Considered a neglected pathogen until the last 2 decades, an increase in the availability of genetic data of hepatitis D virus (HDV) strains around the world has been noticed recently, resulting in the proposition of different classifications. Our study aimed to determine the molecular epidemiological profile of HDV isolates circulating in areas of endemicity and non-areas of endemicity in Brazil. Based on the analyzed fragment, HDV-8 sequences clustered out of the clades formed by subgenotypes 8a and 8b might suggest the identification of a novel subgenotype, putatively designated subgenotype 8c. Our findings demonstrate the importance of continuous epidemiological surveillance to map HDV spread pathways and the introduction of imported variants. It also reinforces that as the amount of HDV genomes generated and reported increases, we will have changes in viral classification and, consequently, in our understanding of the dynamics of variability of this viral agent.

Transcriptomic Profile of Canine Mammary Ductal Carcinoma.

Dogs can be excellent models for spontaneous studies about breast cancers, presenting similarities in clinical behavior and molecular pathways of the disease. Thus, analyses of the canine transcriptome can identify deregulated genes and pathways, contributing to the identification of biomarkers and new therapeutic targets, benefiting humans and animals. In this context, this study aimed to determine the transcriptional profile of canine mammary ductal carcinoma and contribute to the clarification of the importance of deregulated molecules in the molecular pathways involved in the disease. Therefore, we used mammary ductal carcinoma tissue samples and non-tumor mammary tissue from the radical mastectomy of six female dogs. Sequencing was performed on the NextSeq-500 System platform. A comparison of carcinoma tissue and normal tissue revealed 633 downregulated and 573 upregulated genes, which were able to differentiate the groups by principal component analysis. Gene ontology analysis indicated that inflammatory, cell differentiation and adhesion, and extracellular matrix maintenance pathways were mainly deregulated in this series. The main differentially expressed genes observed in this research can indicate greater disease aggressiveness and worse prognosis. Finally, the study of the canine transcriptome indicates that it is an excellent model to generate information relevant to oncology in both species.

HLA-DRB1 Polymorphisms and Rheumatologic Manifestations in Chronic Hepatitis C.

BACKGROUND/AIMS: Hepatitis C has been associated with rheumatologic manifestations (HCV-related RM). Clinically, HCV-related RM may be indistinguishable from the symptoms that occur in diffuse connective tissue diseases (DCTD-related RM), making the differential diagnosis difficult. Host genetic factors, such as the Human Leukocyte Antigens (HLA) polymorphisms were associated with HCV infection, however, there are no studies that discriminate between HCVrelated RM and DCTD-related RM. This study focused on verifying associations between HLADRB1 and RM in patients with chronic hepatitis C, aiming to distinguish between DCTD-related RM and HCV-related RM. METHODS: The participants were 152 individuals, of both sexes, aged between 18 and 80 years, and affected by chronic hepatitis C. The patients underwent rheumatologic physical examination and HLA-class II (HLA-DRB1) typing was performed by PCR-SSO (Polymerase Chain Reactionsequence Specific Oligonucleotides). RESULTS: A significant number of patients with rheumatologic complaints (73%) not attributed to other causes was observed. DRB1*08 allele seems to confer protection against RM in chronic hepatitis C. There is no susceptibility association between HLA-DRB1 alleles and RM. CONCLUSION: The absence of association between HLA-DRB1 and the rheumatologic manifestations studied suggests that the pathophysiological pathways of DCTD-related RM and HCV-related RM are distinct.

Differential Plasma Metabolites between High- and Low-Grade Meningioma Cases.

Meningiomas (MGMs) are currently classified into grades I, II, and III. High-grade tumors are correlated with decreased survival rates and increased recurrence rates. The current grading classification is based on histological criteria and determined only after surgical tumor sampling. This study aimed to identify plasma metabolic alterations in meningiomas of different grades, which would aid surgeons in predefining the ideal surgical strategy. Plasma samples were collected from 51 patients with meningioma and classified into low-grade (LG) (grade I; n = 43), and high-grade (HG) samples (grade II, n = 5; grade III, n = 3). An untargeted metabolomic approach was used to analyze plasma metabolites. Statistical analyses were performed to select differential biomarkers among HG and LG groups. Metabolites were identified using tandem mass spectrometry along with database verification. Five and four differential biomarkers were identified for HG and LG meningiomas, respectively. To evaluate the potential of HG MGM metabolites to differentiate between HG and LG tumors, a receiving operating characteristic curve was constructed, which revealed an area under the curve of 95.7%. This indicates that the five HG MGM metabolites represent metabolic alterations that can differentiate between LG and HG meningiomas. These metabolites may indicate tumor grade even before the appearance of histological features.

Nebulized enriched heparin to treat no critical patients with Sars-Cov-2: Triple-blind clinical trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that spreads rapidly, reaching pandemic status, causing the collapse of numerous health systems, and a strong economic and social impact. The treatment so far has not been well established and there are several clinical trials testing known drugs that have antiviral activity, due to the urgency that the global situation imposes. Drugs with specific mechanisms of action can take years to be discovered, while vaccines may also take a long time to be widely distributed while new virus variants emerge. Thus, drug repositioning has been shown to be a good strategy for defining new therapeutic approaches. Studies of the effect of enriched heparin in the replication of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) in vitro assays justify the advance for clinical tests. METHODS AND ANALYSIS: A phase I/II triple-blind parallel clinical trial will be conducted. Fifty participants with radiological diagnosis of grade IIA pneumonia will be selected, which will be allocated in 2 arms. Participants allocated in Group 1 (placebo) will receive nebulized 0.9% saline. Participants allocated in Group 2 (intervention) will receive nebulized enriched heparin (2.5 mg/mL 0.9% saline). Both groups will receive the respective solutions on a 4/4 hour basis, for 7 days. The main outcomes of interest will be safety (absence of serious adverse events) and efficacy (measured by the viral load).Protocols will be filled on a daily basis, ranging from day 0 (diagnosis) until day 8.

A New Method for Next-Generation Sequencing of the Full Hepatitis B Virus Genome from A Clinical Specimen: Impact for Virus Genotyping.

Hepatitis B virus (HBV) is an enveloped virus that induces chronic liver disease. HBV has been classified into eight genotypes (A-H) according to its genome sequence by using Sanger sequencing or reverse hybridization. Sanger sequencing is often restricted to analyzing the S gene and is inaccurate for detecting minority genetic variants, whereas reverse hybridization detects only known mutations. Next-generation sequencing (NGS) is a robust tool for clinical virology with different protocols available. The objective of this study was to develop a new method for the study of viral genetic polymorphisms or more accurate genotyping using genome amplification followed by NGS. Plasma obtained from five chronically infected HBV individuals was used for viral DNA isolation. HBV full-genome PCR amplification was the enrichment method for NGS. Primers were used to amplify all HBV genotypes in three overlapping amplicons, following a tagmentation step and Illumina NGS. For phylogenetic analysis, sequences were extracted from the HBVdb database. We were able to amplify a full HBV genome; further, NGS was shown to be a robust method and allowed better genotyping, mainly in patients carrying mixed genotypes, classified according to other techniques. This new method may be significant for whole genome analyses, including other viruses.

New LncRNAs in Chronic Hepatitis C progression: from fibrosis to hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the world, and about 80% of the cases are associated with hepatitis B or C. Genetic and epigenetic alterations are accumulated over decades of chronic injury and may affect the functioning of tumor suppressor genes and protooncogenes. Studies have evidenced the role of Long non-coding RNAs (LncRNA) with oncogenic or tumor suppressor activities, suggesting a great potential in the treatment, diagnosis or indicator of prognosis in cancer. In this context, the aim of this study was to evaluate the global expression profile lncRNA in hepatic tissue samples with different stages of fibrosis associated with chronic hepatitis C, HCC and normal liver, in order to identify new lncRNAs that could contribute to study the progression of hepatic fibrosis to HCC associated with chronic hepatitis C. RNA-Seq was performed on Illumina NextSeq platform to identify lncRNAs expressed differently in 15 patients with chronic hepatitis C, three patients with HCC and three normal liver specimens. When the pathological tissues (fibrosis and carcinoma) were compared to normal hepatic tissue, were identified 2, 6 e 34 differentially expressed lncRNAs in moderate fibrosis, advanced fibrosis and HCC, respectively. The carcinoma group had the highest proportion of differentially expressed lncRNA (34) and of these, 29 were exclusive in this type of tissue. A heat map of the deregulated lncRNA revealed different expression patterns along the progression of fibrosis to HCC. The results showed the deregulation of some lncRNA already classified as tumor suppressors in HCC and other cancers, as well as some unpublished lncRNA whose function is unknown. Some of these lncRNAs are dysregulated since the early stages of liver injury in patients with hepatitis C, others overexpressed only in tumor tissue, indicating themselves as candidates of markers of fibrosis progression or tumor, with potential clinical applications in prognosis as well as a therapeutic target. Although there are already studies on lncRNA in hepatocellular carcinoma, this is the first study conducted in samples exclusively of HCV-related liver and HCV HCC.

Human platelet antigen-3 polymorphism as a risk factor for rheumatological manifestations in hepatitis C.

INTRODUCTION: Hepatitis C virus (HCV) infection is involved in the pathogenesis of autoimmune and rheumatic disorders. Although the human platelet antigens (HPA) polymorphism are associated with HCV persistence, they have not been investigated in rheumatological manifestations (RM). This study focused on verifying associations between allele and genotype HPA and RM in patients with chronic hepatitis C. METHODS: Patients (159) with chronic hepatitis C of both genders were analyzed. RESULTS: Women showed association between HPA-3 polymorphisms and RM. CONCLUSIONS: An unprecedented strong association between rheumatological manifestations and HPA-3 polymorphism, possibly predisposing women to complications during the disease course, was observed.

Human platelet antigen-3 polymorphism as a risk factor for rheumatological manifestations in hepatitis C

Abstract INTRODUCTION: Hepatitis C virus (HCV) infection is involved in the pathogenesis of autoimmune and rheumatic disorders. Although the human platelet antigens (HPA) polymorphism are associated with HCV persistence, they have not been investigated in rheumatological manifestations (RM). This study focused on verifying associations between allele and genotype HPA and RM in patients with chronic hepatitis C. METHODS: Patients (159) with chronic hepatitis C of both genders were analyzed. RESULTS: Women showed association between HPA-3 polymorphisms and RM. CONCLUSIONS: An unprecedented strong association between rheumatological manifestations and HPA-3 polymorphism, possibly predisposing women to complications during the disease course, was observed.

HPA-1a/1b could be considered a molecular predictor of poor prognosis in chronic hepatitis C.

INTRODUCTION: HPA polymorphism has been associated with HCV presence and fibrosis progression in chronic hepatitis C. However, it is unknown if there is an association between HPA-1 polymorphism and hepatocellular carcinoma (HCC). Therefore, this study aimed to evaluate HPA-1 polymorphism in the presence of HCC. METHODS: PCR-SSP was used to perform HPA genotyping on 76 HCV-infected patients. RESULTS: There was no association between patients with and without HCC. There was significant difference in HPA-1 genotypic frequency distribution between HCC and F1/F2 fibrosis degree. CONCLUSIONS: The HPA-1a/1b polymorphism appears to be more associated with liver damage progression than with HCC presence.

Influence of the HIV GWG variant in the HIV infection progression in mono and HCV coinfected patients.

The HIV subtype B is the most frequent in Brazil. The HIV subtype B' codes the amino acids glicine-tryptophan-glicine (GWG) instead of glicine-proline-glicine on the tip of gp120 V3 loop. This variant was associated to a slower HIV progression in mono-infected patients; however, there is no information in coinfected patients. This study evaluated the infection progression of HIV variant B' on the hepatitis C virus presence. RNA isolated from plasma of the 601 infected patients were used to human immunodeficiency virus (HIV) subtyping and to classify the virus according their syncytium-inducing ability. The HIV infection progression was evaluated by clinical and laboratorial data. The results showed a significant association between HIV B' variant and CD4 count and time of AIDS in HIV mono-infected patients. Notwithstanding the fact that we did not find a direct association between GWG variant and AIDS and in HIV coinfected patients no mitigating effect due to GWG presence was found. We did observe that the association between GWG variant and CD4 counts is lost in coinfected patients. This is first work showing influence of the HIV GWG variant in coinfected patients. Nevertheless, the presence of the GWG variant can indicate a better prognostic in the mono-infected patients.

Explanation for the signs and symptoms of tooth eruption: mast cells.

This study contributes to the understanding of the mechanisms associated with signs and symptoms of tooth eruption, by investigating the presence of mast cells in pericoronal tissues during the intraosseous (Group 1) and submucosal (Group 2) phases of eruption. We compared findings for these two groups with each other and with those for the oral mucosa (Group 3). In each group, 14 specimens were analyzed microscopically after hematoxylin and eosin staining and immunohistochemical analysis of c-Kit and tryptase expression. Results revealed that the number and density of mast cells is different in follicular tissues according to the eruption phase, which may mean that: 1) masticatory trauma of the oral mucosa and dental follicles in the submucosa may explain why reduced enamel epithelium exposes enamel to the cells of the connective tissue; 2) exposure of antigenic enamel proteins might correspond to the release of sequestered antigens, which may lead to the interaction of IgE and a greater number of mast cells in the region; and 3) the consequent degranulation and the local release of mediators, such as histamine, leukotrienes, prostaglandins, proteases, cytokines and growth factors, contribute to the understanding of signs and symptoms associated with tooth eruption.

Explanation for the signs and symptoms of tooth eruption: mast cells

Abstract This study contributes to the understanding of the mechanisms associated with signs and symptoms of tooth eruption, by investigating the presence of mast cells in pericoronal tissues during the intraosseous (Group 1) and submucosal (Group 2) phases of eruption. We compared findings for these two groups with each other and with those for the oral mucosa (Group 3). In each group, 14 specimens were analyzed microscopically after hematoxylin and eosin staining and immunohistochemical analysis of c-Kit and tryptase expression. Results revealed that the number and density of mast cells is different in follicular tissues according to the eruption phase, which may mean that: 1) masticatory trauma of the oral mucosa and dental follicles in the submucosa may explain why reduced enamel epithelium exposes enamel to the cells of the connective tissue; 2) exposure of antigenic enamel proteins might correspond to the release of sequestered antigens, which may lead to the interaction of IgE and a greater number of mast cells in the region; and 3) the consequent degranulation and the local release of mediators, such as histamine, leukotrienes, prostaglandins, proteases, cytokines and growth factors, contribute to the understanding of signs and symptoms associated with tooth eruption.

Resumo Para contribuir com a compreensão dos mecanismos relacionados à sintomatologia e aos sinais associados à erupção dentária, investigou-se a presença de mastócitos nos tecidos pericoronários na fase intraóssea (Grupo 1) e submucosa (Grupo 2), comparando-os entre si e com a mucosa bucal (Grupo 3). Em cada grupo, 14 espécimes foram analisados microscopicamente em cortes corados com hematoxilina e eosina, e imunocitoquimicamente marcados com Ckit e Triptase. Pelos resultados obtidos, concluiu-se que a quantidade/densidade dos mastócitos é diferente nos tecidos foliculares de acordo com a fase de erupção, o que permite inferir que: 1) O traumatismo decorrente da mastigação sobre o conjunto "mucosa bucal com o folículo pericoronário na submucosa" pode explicar porque o epitélio reduzido exporia o esmalte às células do tecido conjuntivo; 2) A exposição das proteínas do esmalte com propriedades antigênicas corresponderia à liberação de antígenos sequestrados que levariam à interação de IgE e mastócitos em número aumentado na região; e 3) A consequente degranulação e liberação de mediadores no local, como histamina, leucotrienes, prostaglandinas, proteases, citocinas e fatores de crescimento, contribuem para a compreensão dos sinais e sintomatologia atribuídos à erupção dentária.

HPA-1a/1b could be considered a molecular predictor of poor prognosis in chronic hepatitis C

Abstract INTRODUCTION: HPA polymorphism has been associated with HCV presence and fibrosis progression in chronic hepatitis C. However, it is unknown if there is an association between HPA-1 polymorphism and hepatocellular carcinoma (HCC). Therefore, this study aimed to evaluate HPA-1 polymorphism in the presence of HCC. METHODS: PCR-SSP was used to perform HPA genotyping on 76 HCV-infected patients. RESULTS: There was no association between patients with and without HCC. There was significant difference in HPA-1 genotypic frequency distribution between HCC and F1/F2 fibrosis degree. CONCLUSIONS: The HPA-1a/1b polymorphism appears to be more associated with liver damage progression than with HCC presence.

Hypermethylation of BRCA1 Gene in Meningioma in Elderly Males.

BACKGROUND/AIM: Breast cancer 1, early onset (BRCA1) gene is expressed in the cells of the breast and other tissues, where it plays a role in cell-cycle regulation, transcription, repair of DNA double-stranded breaks, ubiquitination, transcriptional regulation as well as other functions, such as cell response regulation to mitogenic signals triggered by estrogens. Considering that meningioma shows greater tumor growth during pregnancy, can express estrogen receptors and proliferate in response to estrogenic stimulation, the hypothesis that this type of tumor may share molecular mechanisms that involve exposure to estrogen should be investigated. Therefore, the aim of the present study was to investigate the BRCA1 gene methylation profile in meningioma. MATERIALS AND METHODS: Methylation-specific polymerase chain reaction (PCR) assay was performed on 50 meningioma samples from male and female patients. Statistical analysis was carried out using Fisher's exact test. RESULTS: The most important finding of this study was that 100% of the male patients over 55 years with meningioma showed BRCA1 methylated in their tumor cells. CONCLUSION: The silencing of BRCA1 through hypermethylation seems to play an important role in meningioma.

HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection.

Variability of the HIV reverse transcriptase (RT) and protease (PR) genes has been used as indicators of drug resistance and as a mean to evaluate phylogenetic relationships among circulating virus. However, these studies have been carried in HIV mono-infected populations. The goal of this study was to evaluate, for the first time, the HIV PR and RT sequences from HIV/HBV and HIV/HCV co-infected patients. HIV PR and RT genes were amplificated and sequenced to resistance analysis. The bioinformatics analysis was performed to infer about sequences clustering and molecular evolution. The results showed that the most frequent amino acid substitutions in RT were L214F (67.6%), I135T (55.9%), and in PR was V15I (41.2%). The molecular clock analysis showed that the HIV circulating in co-infected patients were separated in two clusters in the years 1999-2000. Some patients included as HIV mono-infected according patients' medical records and inside the co-infected cluster were, in fact, co-infected by PCR analysis. Analysis of the decision trees showed susceptibility to lamivudine and emtricitabine were important attribute to characterize co-infected patients. In conclusion, the results obtained in this study suggest, for the first time, that HIV RT and PR genes variability could be a genetic biomarker to coinfection.

Hepatitis D infection in Brazil: Prevalence and geographical distribution of anti-Delta antibody.

In Brazil, the Amazon Basin is endemic for hepatitis D virus (HDV) infection; however, studies in other regions of the country are scarce. This study aims to map the seroepidemiological situation of anti-Delta antibodies in chronic hepatitis B carriers in all five Brazilian geographic regions. Serum samples from 1240 HBsAg positive individuals (55.4% men; mean age 43.1 ± 13.4 years) from 24 of 26 Brazilian states were tested for the presence of anti-Delta antibodies using a commercial immunoassay. Anti-Delta antibodies were detected in 40 samples (3.2%; 52.5% female; mean age of 38.1 ± 13.8 years). Age less than 20 years was significantly associated with anti-HDV positivity (P < 0.001). The distribution of anti-Delta differed markedly in the diverse regions of the country. The highest prevalence of anti-HDV was found in the North (8.5%; P < 0.001), followed by Central West (2.5%), Southeast (1.7%), Northeast (0.8%), and South (0.0%). Anti-Delta antibodies were detected in 12 states, but more than 60% of the positive cases were observed in two states, Amazonas and Acre, located in the western portion of the Amazon region. The overall HDV prevalence of 3.2% emphasizes that HDV is far from being a disease under control in Brazil. Despite the low HDV prevalence in non-endemic regions, this infection persists as a major concern in two states (Acre and Amazonas) in the north of the country, indicating that a continuous epidemiological surveillance program should be implemented in all Brazilian regions.

The intricate interplay between MSI and polymorphisms of DNA repair enzymes in gastric cancer H.pylori associated.

Gastric cancer is the fourth most common type of cancer worldwide. Helicobacter pylori is a well-established risk factor and may cause injuries to genomic integrity through an inefficient DNA repair. This study aimed to examine the influence of polymorphisms in DNA repair enzymes using markers for microsatellite instability (MSI). Polymorphisms of DNA repair enzymes were detected by PCR-RFLP and MSI, by high resolution melt (HRM) analysis. Helicobacter pylori detection and genotyping were accomplished by PCR. MSI was observed in 47.5% of the cases and it was associated with the ERCC1 polymorphic allele, whereas MSI-H was associated with the XRCC3 heterozygous genotype. MSI was more frequent in intestinal gastric cancer (IGC), where it was associated with ERCC1 or RAD51 polymorphic alleles. Also, MSI-H was associated with the XRCC3 heterozygous. In diffuse gastric cancer (DGC), almost all of MGMT polymorphic genotype carriers showed MSI. Helicobacter pylori was positive in 94% of the cases and the most virulent strains were associated with MSI, mainly MSI-H. When the subtypes were considered, these associations were found only in the IGC and associated with more virulent strains. Among the cases with microsatellite instability, IGC showed a correlation between the XPD wild-type and the ERCC1 polymorphic allele, and all of them were infected by the most virulent strains. On the other hand, in DGC, the XPD polymorphic allele was correlated with the XRCC3 wild-type with no prevalence of H.pylori virulence. Our data demonstrated that polymorphisms in repair enzymes can interfere with the efficiency of the repair process, but it differs depending on the histological subtype and H.pylori involvement. Besides nucleotide excision repair, base excision repair and mismatch repair pathway, the homologous recombination are also involved.

Nationwide overview of the distribution of hepatitis B virus genotypes in Brazil: a 1000-sample multicentre study.

The influence of hepatitis B virus (HBV) genotypes in the natural history of the disease and its response to antiviral treatment have been addressed in many studies. In Brazil, studies on HBV genotype circulation have been restricted to specific population groups and states. Here, we have conducted a nationwide multicentre study with an unprecedented sample size representing all Brazilian regions in an effort to better understand the viral variants of HBV circulating among chronic carriers. Seven HBV genotypes were found circulating in Brazil. Overall, HBV/A was the most prevalent, identified in 589 (58.7 %) samples, followed by HBV/D (23.4 %) and HBV/F (11.3 %). Genotypes E, G, C and B were found in a minor proportion. The distribution of the genotypes differed markedly from the north to the south of the country. While HBV/A was the most prevalent in the North (71.6 %) and Northeast (65.0 %) regions, HBV/D was found in 78.9 % of the specimens analysed in the South region. HBV/F was the second most prevalent genotype in the Northeast region (23.5 %). It was detected in low proportions (7 to 10 %) in the North, Central-West and Southeast regions, and in only one sample in the South region. HBV/E was detected in all regions except in the South, while monoinfection with HBV/G was found countrywide, with the exception of Central-West states. Our sampling covered 24 of the 26 Brazilian states and the Federal District and is the first report of genotype distribution in seven states. This nationwide study provides the most complete overview of HBV genotype distribution in Brazil to date and reflects the origin and plurality of the Brazilian population.

Platelet-derived growth factor A mRNA in platelets is associated with the degree of hepatic fibrosis in chronic hepatitis C.

INTRODUCTION:: Transforming growth factor beta 1 (TGFB1) and platelet-derived growth factor (PDGF) are the main cytokines related to hepatic fibrogenesis. METHODS:: RNA isolated from the platelets and hepatic tissue of 43 HCV carriers was used for quantitative polymerase chain reaction to determine TGFB1, PDGFA, and PDGFB RNA expression. RESULTS:: The mRNA expression of PDGFA in platelets was significantly lower in the group with advanced fibrosis than in the group with early-stage fibrosis. TGFB1 was more frequently expressed in platelets than in hepatic tissue, which was different from PDGFB. CONCLUSIONS:: A pathway mediated by overexpression of TGFB1 via PDGFA in megakaryocytes could be involved in the development of fibrosis.