Caracterización del paciente con Hepatitis C bajo control en el Sistema Público de Salud, Chile. Año 2016 -2017- / Characterization of hepatitis C patients under treatment in the Public Health System, Chile-2016

At the 67° World Health Assembly (WHA67.6), member states are encouraged to undertake measures to ensure and strengthen surveillance, prevention, access to treatment and control of viral hepatitis in all countries. In this context- and although in Chile hepatitis C is considered a low endemic pathology- efforts have been made to improve the lives of people infected by this virus. In the process of inclusion of new direct-action therapies such as Explicit Guarantees in Health (GES), it was necessary to know the real demand, as well as some important variables for decision-making. Methodology: In 2016, the Ministry of Health requested to the centers of hepatitis C of the public health system of the country, to report in Excel spreadsheets the list of patients under control, including variables of clinical-epidemiological interest. Sensitive data from these cases guaranteed throughout the process. Descriptive analysis of the profile of the patient, genotype, comorbidities, as well as liver transplantation, the result of previous treatment and candidates for new therapies according to prioritization criteria, established in GES regulation. In the results the characterization of the patients is described: the age is concentrated between 45 and 69 years old, without greater difference by sex, the most common genotype is 1 with 60% and 18% for genotype 3, 35% has cirrhosis, 21% has esophageal varicose veins, 6% HCV/HIV co-infection, 0.8% HCV/HBV co-infection, 7% with hemophilia.

En la 67ª Asamblea Mundial de la Salud (WHA67.6) se recomienda a los estados miembros emprender medidas para garantizar y fortalecer la vigilancia, prevención, acceso al tratamiento y control de las hepatitis virales en todos los países. En este contexto, y pese a que en Chile se considera la hepatitis C como una patología de baja endemia, se han realizado esfuerzos para mejorar la vida de las personas infectadas por este virus. En el proceso de inclusión de las nuevas terapias de acción directa como garantías explícitas en Salud (GES), se requirió conocer la demanda real, así como algunas variables importantes para la toma de decisiones. Metodología: El año 2016 desde el Ministerio de Salud se solicitó a los centros tratantes de hepatitis C del sistema público de salud del país, informar el listado de pacientes bajo control, incluyendo variables de interés clínico epidemiológico requeridas en planillas Excel. Se garantizó en todo el proceso los datos sensibles de estos casos. Se realizó un análisis descriptivo del perfil del paciente, genotipo, comorbilidades, así como trasplante hepático, resultado de tratamiento anterior y candidatos a nuevas terapias según criterios de priorización, establecidos en la norma GES. En los resultados se describe la caracterización de los pacientes: la edad se concentra entre los 45 y 69 años, sin mayor diferencia por sexo, el genotipo más común es el 1 con 60% y 18% para el genotipo 3, 35% presenta cirrosis, 21% presenta várices esofágicas, 6% coinfección VHC/VIH, 0,8% coinfección VHC/VHB, 7% con hemofilia.

Treatment of hepatitis C virus genotype 3 infection with direct-acting antiviral agents

Hepatitis C virus (HCV) genotype 3 is responsible for 30.1% of chronic hepatitis C infection cases worldwide. In the era of direct-acting antivirals, these patients have become one of the most challenging to treat, due to fewer effective drug options, higher risk of developing cirrhosis and hepatocellular carcinoma and lower sustained virological response (SVR) rates. Currently there are 4 recommended drugs for the treatment of HCV genotype 3: pegylated interferon (PegIFN), sofosbuvir (SOF), daclatasvir (DCV) and ribavirin (RBV). Treatment with PegIFN, SOF and RBV for 12 weeks has an overall SVR rate of 83–100%, without significant differences among cirrhotic and non-cirrhotic patients. However, this therapeutic regimen has several contraindications and can cause significant adverse events, which can reduce adherence and impair SVR rates. SOF plus RBV for 24 weeks is another treatment option, with SVR rates of 82–96% among patients without cirrhosis and 62–92% among those with cirrhosis. Finally, SOF plus DCV provides 94–97% SVR rates in non-cirrhotic patients, but 59–69% in those with cirrhosis. The addition of RBV to the regimen of SOF plus DCV increases the SVR rates in cirrhotic patients above 80%, and extending treatment to 24 weeks raises SVR to 90%. The ideal duration of therapy is still under investigation. For cirrhotic patients, the optimal duration, or even the best regimen, is still uncertain. Further studies are necessary to clarify the best regimen to treat HCV genotype 3 infection.

ANALYSIS OF POLYMORPHISMS IN THE INTERLEUKIN 18 GENE PROMOTOR (-137 G/C AND -607 C/A) IN PATIENTS INFECTED WITH HEPATITIS C VIRUS FROM THE BRAZILIAN AMAZON / Análise do polimorfismo na região promotora do gene da interleucina 18 (-137 G/C e -607 C/A) em pacientes portadores do vírus da hepatite C na Amazônia Brasileira

BackgroundThe hepatitis C virus has been recognized as the leading cause of chronic liver disease in the world. Host genetic factors have been implicated in the persistence of hepatitis C virus infection. Single nucleotide polymorphisms at positions -607 C/A (rs1946518) and -137 G/C (rs187238) in the IL-18 gene promoter have been suggested to be associated with delayed hepatitis C virus clearance and persistence of the disease.ObjectiveIdentify these polymorphisms in a population infected with hepatitis C virus from the Brazilian Amazon region.MethodsIn a cross-sectional analytical study conducted in Belém, Pará, Brazil, 304 patients infected with hepatitis C virus were divided into two groups: group A, patients with persistent infection; group B, patients with spontaneous clearance. The control group consisted of 376 volunteers not infected with hepatitis C virus. Samples were analyzed by RT-PCR for the detection of viral RNA and by RFLP-PCR to evaluate the presence of the -137 G/C and -607 C/A IL-18 gene promoter polymorphisms.ResultsComparison of polymorphism allele frequencies between the patient and control groups showed a higher frequency of allele C at position -607 among patients (P=0.02). When the association between the polymorphisms and viral infection was analyzed, patients carrying genotype C/A at position -607 were found to be at higher risk of persistent hepatitis C virus infection (P=0.03).ConclusionThe present results suggest a possible role of the -607 IL-18 gene promoter polymorphism in the pathogenesis of hepatitis C virus infection.

ContextoO vírus da hepatite C é reconhecido como a maior causa de doença hepática crônica no mundo. Fatores genéticos do hospedeiro têm sido implicados na persistência da infecção pelo vírus da hepatite C. Polimorfismos de nucleotídeos únicos na posição -607 C/A (rs1946518) e -137 G/C (rs187238) na região promotora do gene da IL-18 têm sido evidenciados em alguns estudos que sugerem sua associação ao atraso na depuração do vírus da hepatite C e na persistência da doença.ObjetivoO presente estudo pretende identificar esses polimorfismos em uma população da região da Amazônia Brasileira infectada pelo vírus da hepatite C.MétodosEstudo do tipo transversal analítico no município de Belém-PA foi realizado em 304 pacientes infectados pelo vírus da hepatite C, divididos em: grupo A, pacientes com infecção persistente; grupo B, pacientes que apresentaram clareamento viral. Como grupo controle participaram 376 voluntários não infectados pelo vírus da hepatite C. As amostras foram submetidas à RT-PCR, para detecção do RNA viral e, posteriormente, à RFLP-PCR para avaliação do polimorfismo na região promotora do gene da IL-18, nas posições -137 G/C e -607 C/A.ResultadosA comparação das frequências dos polimorfismos no grupo de pacientes com o grupo controle demonstrou uma maior frequência do alelo C na posição -607 entre os pacientes (P=0,02) que no grupo controle. Na análise da associação dos polimorfismos com a infecção viral foi obtido que portadores do genótipo C/A na posição -607 possuíam maior risco de infecção persistente pelo vírus da hepatite C (P=0,03).ConclusãoNossos resultados sugerem uma possível implicação do polimorfismo da região promotora -607 do gene IL-18 na patogenia da infecção pelo vírus da hepatite C.

Asociación entre polimorfismos en los genes PNPLA3 y TM6SF2 y presencia de fibrosis en pacientes con infección crónica por virus hepatitis C / The association between polymorphisms in the genes PNPLA3 and TM6SF2 and the presence of fibrosis in patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV) is a globally prevalent pathogen and a leading cause of death and morbidity. The most recent estimates of disease burden show an increase in seroprevalence over the last 15 years to 2.8 percent, equating to >185 million infections worldwide. Persistent hepatitis C infection is associated with the development of liver cirrhosis, hepatocellular cancer, liver failure and death. The magnitude of disease progression in chronic infection varies significantly among individuals. Several factors have been recognized as being associated with the progression of HCV-related liver fibrosis and with clinical outcomes. As liver fibrosis progression remains variable between individuals with similar environmental or virological risks, host genetic predispositions have been suggested as another critical determinant. The single nucleotide polymorphisms in Patatin-like phospholipase domain-containing 3 (PNPLA3) and Transmembrane 6 Superfamily Member 2 (TM6SF2) genes are genetic determinants of nonalcoholic fatty liver disease, in terms of inflammation and fibrosis. The possible action of the PNPLA3 and TM6SF2 polymorphisms on fibrosis development in chronic hepatis C is being studied, with controversial results.

Aplicabilidade do sangue seco em papel de filtro para estudos de prevalência da infecção pelo vírus da hepatite C em grupos / Appllicability of dried blood spots for prevalence estudies of hepatities c virus infection in differente groups

O diagnóstico da infecção pelo vírus da hepatite C (HCV) emprega testes imunoenzimáticos emoleculares em amostras de soro obtidas a partir de punção venosa. O uso de fluidos alternativos,como o sangue seco em papel de filtro (SSPF) pode ser uma opção vantajosa para o diagnóstico,pois a coleta é menos invasiva e o material pode ser armazenado e transportado em temperaturaambiente. O objetivo deste estudo foi determinar a utilidade do SSPF para diagnóstico e estudos deprevalência da infecção pelo HCV em diferentes regiões geográficas do Brasil e avaliar os fatores derisco associados. Para isto, foram incluídos indivíduos provenientes de 4 regiões geográficas doBrasil (Norte, Nordeste, Centro-Oeste e Sudeste), divididos em 3 grupos: (I) Área de baixaendemicidade (n=1465); (II) Indivíduos com alta vulnerabilidade para aquisição da infecção pelo HCV(n=491); (III) Área de alta endemicidade (n=254). A detecção do anti-HCV foi feita utilizando umensaio imunoenzimático comercial (Murex anti-HCV v.4.0, Diasorin, Itália), onde o protocolo dofabricante foi seguido para amostras de soro e para as amostras de SSPF foi aumentado em 20vezes (volume final igual a 100µL). Amostras de soro anti-HCV reagentes foram submetidas adetecção do HCV RNA por PCR em tempo real comercial (Abbot Real time HCV, Abbott, EUA) eensaios de genotipagem (Abbott Real Time Genotype II). Para análise dos fatores de riscoassociados à infecção pelo HCV, foram incluídas variáveis sociodemograficas e de comportamentode risco, onde analise bivariada foi realizada no grupo III e análises descritivas foram feitas emtodos os grupos. O valor de p <0,05 foi considerado estatisticamente significante. A concordânciaentre resultados de detecção de anti-HCV em soro e SSPF na população total foi igual a 99,7 por cento comvalor de kappa igual a 0,930...

The diagnosis of hepatitis C virus (HCV) infection uses enzyme immunoassays and moleculartests in serum samples obtained from venipuncture. The use of alternative fluids such as driedblood spots (DBS) could be an attractive alternative for diagnosis, due to the less invasivecollection and the material can be stored and transported at room temperature. The aim of thisstudy was to determine the usefulness of the DBS for diagnosis and prevalence studies of HCVinfection in different geographical regions of Brazil and to evaluate the associated risk factors.So, individuals from four geographic regions in Brazil (North, Northeast, Midwest andSoutheast) were included and divided into 3 groups: (I) Low endemicity area (n=1465); (II)Individuals at high risk for acquisition of HCV infection (n=491); (III) High endemicity area(n=254). Anti-HCV detection was performed using a commercial enzyme immunoassay (Murexanti-HCV v.4.0, DIASORIN, Italy), following the manufacturer's protocol for serum samples andfor DBS samples, the volume was 20fold increased (final volume equal to 100µL). Reactive antiHCVserum samples were submitted to real time PCR for HCV RNA detection (Abbott HCV realtime, Abbott, USA) and genotyping assay (Abbott Real Time Genotype II). For analyze of riskfactors associated to HCV infection, sociodemographic and behavior risk variables wereincluded, where bivariate analysis were done for group III and descriptive analysis wereconducted for all groups. P value < 0.05 was considered statistically significant...

Personalized medicine and the clinical laboratory / Medicina personalizada e o laboratório clínico

Personalized medicine is the use of biomarkers, most of them molecular markers, for detection of specific genetic traits to guide various approaches for preventing and treating different conditions. The identification of several genes related to heredity, oncology and infectious diseases lead to the detection of genetic polymorphisms that are involved not only in different clinical progression of these diseases but also in variations in treatment response. Currently, it is possible to detect these polymorphisms using several methodologies: detection of single nucleotide polymorphisms using polymerase chain reaction methods; nucleic acid microarray detection; and nucleic acid sequencing with automatized DNA sequencers using Sanger-derived methods and new generation sequencing. Personalized medicine assays are directed towards detecting genetic variations that alter interactions of drugs with targets or the metabolic pathways of drugs (upstream and downstream) and can be utilized for the selection of drug formulations and detect different immunogenicities of the drug. Personalized medicine applications have already been described in different areas of Medicine and allow specific treatment approaches to be applied to each patient and pathology according to the results of these assays. The application of such a protocol demands an increasing interaction between the clinical laboratory and the clinical staff. For its implementation, a coordinated team composed of basic researchers and physicians highly specialized in their areas supported by a highly specialized team of clinical analysts particularly trained in molecular biology assays is necessary.

Medicina personalizada é o uso de biomarcadores, em sua maioria marcadores moleculares, para a detecção de traços genéticos específicos, a fim de orientar diversas abordagens para a prevenção e o tratamento de diferentes doenças. A identificação de vários genes relacionados a doenças hereditárias, oncológicas e infecciosas permite a detecção de polimorfismos genéticos que estão envolvidos em diferentes evoluções clínicas dessas doenças, bem como com variações na resposta ao tratamento. Atualmente, já é possível detectar esses polimorfismos utilizando diversas metodologias: a detecção de polimorfismos de nucleotídeo único pela reação de polimerização em cadeia; a detecção de microarranjos de ácidos nucleicos; e o sequenciamento de ácidos nucleicos com sequenciadores de DNA automatizados usando métodos derivados de sequenciamento Sanger ou de nova geração. Os ensaios de medicina personalizada são dirigidos para detectar variações genéticas que alteram interações de fármacos com alvos ou vias metabólicas de fármacos (anabólicas e catabólicas), podendo ser utilizados para a seleção de formulações farmacêuticas e para detectar diferentes imunogenicidades da droga. As aplicações de medicina personalizada já foram descritas em várias áreas da Medicina e permitem que abordagens de tratamento específicas sejam aplicadas para cada paciente e para cada doença, de acordo com os resultados dos ensaios utilizados. A aplicação de um protocolo desse tipo exige uma relação intensa entre o laboratório e o corpo clínico. Para sua execução, é necessária uma equipe coordenada, composta por investigadores de pesquisa básica e médicos altamente especializados em suas áreas, apoiada por um time bastante especializado de analistas clínicos treinados em testes de biologia molecular.

Association between insulin resistance and sustained virologic response in hepatitis C treatment, genotypes 1 versus 2 and 3: systematic literature review and meta-analysis

BACKGROUND/AIMS: Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. METHODS: Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCVRNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. RESULTS: Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. CONCLUSION: This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype.

Hepatitis C genotype 4: genotypic diversity, epidemiological profile, and clinical relevance of subtypes in Saudi Arabia

Hepatitis C virus genotypes 4 [HCV-4] is the most prevalent genotype in Saudi Arabia, although it's various subtypes, mode and route of transmission remains unknown. The aim of this study was to analyze [i] the variability of the HCV-4 subtypes, the route and source of HCV transmission and [ii] the influence of HCV-4 subtypes on their therapeutic response. Sixty-four HCV-4 patients were analyzed retrospectively for the prevalence of various sub-genotypes and the possible mode of transmission, and it was correlated with their treatment response to pegylated interferon [PEG-IFN] alpha-2a and ribavirin therapy. Positive history of blood or blood products transfusion was noted in 22 patients [34%], hemodialysis in 10 patients [15.6%], surgery in 7 patients [11%], and unknown etiology in 25 patients [39%]. Prevalence of HCV-4 subtypes was 4a = 48.4% [31/64], 4d = 39% [25/64], 4n = 6.25% [4/64], and remaining combined [4m, 4l, 4r, 4o] 6.25% [4/64]. No significant correlation between subtypes and the source of transmission was recognized [P = 0.62]. Sustained virological response in all HCV-4 patients was 64% [41/64], while in each subtypes separately it was 4a 77.4% [24/31], 4d 52% [13/25], and combined [4n, 4m, 4l, 4r, 4o] 62.5% [5/8] [P = 0.046]. No obvious cause for the mode of HCV transmission was noted in majority of the patients. No significant correlation was observed between HCV-4 subtypes and the source of HCV infection. 4a and 4d subtypes were the most common in Saudi Arabia, and patients infected with 4a subtype responded significantly better to combination therapy than to 4d subtype

Hepatitis C virus genotype distribution in Egyptian diabetic patients: a preliminary study

There is controversy regarding whether a specific hepatitis C virus [HCV] genotype is associated with diabetes mellitus. This study aimed to investigate HCV genotype distribution in diabetics and its relation to some clinical and laboratory variables in HCV-positive diabetic versus non-diabetic Egyptians in East Delta. The study included 100 HCV-positive patients of which 66 were diabetic in addition to 35 healthy adults as a control group. Clinical assessment, laboratory measurements of plasma glucose, insulin, C-peptide, C-reactive protein [CRP], tumour necrosis Factor-alpha [TNF-alpha] and liver functions [alanine aminotransferase [ALT], aspartate aminotransferase [AST] and gamma-glutamyltransferase [GGT]] as well as HCV genotype determination were done, and AST/platelet ratio index [APRI] and Homoeostasis Model of Assessment-Insulin Resistance [HOMA-IR] were calculated. The main results were the presence of HCV genotype 3, in 31.8% of the diabetic group and in 26.5% of the non-diabetic group, while the remainder of cases had genotype 4, the predominant genotype in Egypt. This is the first report of the presence of HCV genotype 3 in about 30% of an Egyptian cohort. However, there was no significant difference in genotype distribution between both groups. Further, there were significantly higher values of HOMA-IR, insulin and C-peptide in HCV-positive groups in comparison to the control group, while TNF-alpha was significantly higher in the HCV-positive diabetic group. However, there were no significant differences between both genotypes regarding these parameters. Although this study reveals for the first time the presence of HCV genotype 3 in a significant percentage of a group of Egyptian patients, where the majority were diabetic, the association between diabetes and certain HCV genotypes could not be confirmed on the basis of our findings. Hence, taking into consideration the impact of such a finding on the treatment decisions of those patients, further studies are warranted to explore these findings to a greater extent

Epidemiological features of patients infected with HCV genotype 4 in Poland

Hepatitis C genotype 4 [HCV-4] is considered to be rare outside northern Africa and southern Europe. To describe the epidemiological characteristics of patients infected with HCV-4 in Poland. The study group included 290 patients with HCV-related chronic liver disease and intravenous drug users with HCV infection recruited in years 2002-2006 in Podlaskie region, North-Eastern Poland. In all cases, HCV infection was confirmed by HCV-RNA detection by qualitative nested RT-PCR. HCV genotype was determined by 5'UTR sequencing and comparison with known genotype-specific sequences. HCV 4 was found in 45 [15.5%] of 290 HCV-infected and HCV RNA-positive individuals. 60% of HCV 4 infections occurred in intravenous drug users; 51% of HCV 4-infected patients were also HIV-positive. Among 119 patients whose source of infection was other than drug use, there were 16 [10.5%] HCV 4 cases. Seven [46%] of 13 HCV 4-positive and HIV-negative patients who received combined antiviral treatment had sustained viral response. HCV 4 exists in Eastern Poland, and the infection is frequently related to intravenous drug use and accompanied by HIV infection. HCV 4 also causes a proportion of non-drug-related HCV infections

Association of MnSOD Ala16Val genotype and activity with hepatocellular carcinoma risk in HCV-infected Egyptian patients

Hepatocellular carcinoma [HCC] is the most common primary malignant tumour of the liver. Chronic infection with hepatitis C virus [HCV] is a risk factor for HCC occurrence. HCV infection causes oxidative stress in hepatic cells through overproduction of reactive oxygen species [ROS] that cause carcinogenesis. Manganese superoxide dismutase [MnSOD] is an antioxidant enzyme that quenches free radicals. Ala16Val MnSOD polymorphism has been associated with cancer. It results from substitution of T to C at nucleotide 47 causing a change of valine to alanine on the 16th residue of 24-amino acid of mitochondrial-targeting sequence [MTS]of MnSOD. This work aimed to assess the relationship between MnSOD Ala16Val genotype and activity and HCC development in HCV-infected Egyptian patients. This study was conducted on 75 HCV-infected HCC patients, 24 asymptomatic HCV-infected patients and 58 healthy controls. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism [PCR/RFLP] analysis. MnSOD activity was measured using a superoxide dismutase assay kit. The HCC group included 56 males and 19 females. The mean +/- standard deviation [SD] of their age was 53.3 +/- 1.85 years. The Ala/Ala genotype frequency in HCC patients [36.0%] was significantly higher than that in asymptomatic HCV-infected patients [12.5%, p= 0.029] and in the healthy controls [18.9%, p=0.031]. There was a significant difference between MnSOD activity in HCC patients and those in asymptomatic HCV-infected patients and healthy control [p=0.000]. Moreover, there was a highly significant increase in MnSOD activity in HCC patients with Ala/Ala and Val/Ala than in those with Val/Val genotypes [p=0.007]. There is an evidence of association between Ala16Val MnSOD polymorphism and HCC occurrence in HCV-infected Egyptian patients. Furthermore, serum MnSOD activity was significantly higher in those patients compared to control subjects

Association of HLA alleles with hepatitis C infection in Maharashtra, western India.

Background & objectives: Host genetic diversity is believed to contribute to the spectrum of clinical outcomes in hepatitis C virus (HCV) infection. The present study aimed at finding out the frequencies of HLA class I and class II alleles of HCV infected individuals from western India. Methods: Forty three clinically characterized anti-HCV positive patients from Maharashtra were studied for HLA A, B, C, DRB1 and DQB1 alleles by PCR- sequence specific primer (SSP) typing method and compared with 67 and 113 ethnically matched, anti-HCV negative healthy controls from western India. Results: Our analysis revealed an association of HLA alleles HLA A*03 (OR= 16.69, EF, 0.44, P=7.9E-12), A*32 (OR= 1474, EF 0.21, P=1.8E-9), HLA B*15 (OR=14.11, EF 0.39, P=2.18E-10), B*55 (OR= 12.09, EF 0.07, P=0.005), Cw*16 (OR= 7.45, EF 0.12, P=0.001), Cw*18 (OR= 402, EF 0.05, P=0.003), DRB1*03 (OR= 4.01, EF 0.08, P=0.01) and DQB1*03 (OR= 3.02, EF 0.22, P=0.001), with HCV infection. HLA II locus haplotype DRB1*11-DQB1*03 (HF=17.64, OR=5.16, P=0.0001) was significantly increased among HCV infected individuals. Interpretation & conclusions: Our data suggest that among the western Indian population, certain HLA alleles or associated haplotype influence HCV infection as a host genetic factor.

Variações nas regiões 5’ não traduzida e na proteína não estrutural NS5A do vírus da Hepatite C em pacientes infectados com o genótipo 1 / Variations in the 5 'untranslated and non-structural protein NS5A of hepatitis C virus in patients infected with genotype 1

Embora exibindo considerável variabilidade genética, a região 5' não codificante (5'RNC) do genoma viral é relativamente bem conservada entre todos os genótipos Existem evidências da presença nestes domínios de um sítio de entrada interno do ribossomo (IRES) que permite a tradução cap-independente do RNA viral. A variabilidade na região da proteína não estrutural NS5A, designada “Região Determinante da Suscetibilidade ao interferon” (ISDR), foi associada à resistência ou sensibilidade a terapia com interferon-α. A partir das seqüências obtidas, foram realizadas predições da estrutura secundária da 5' RNC pelos programas RNAfold, RNApdist e RNAshapes. Também foram realizados experimentos de transfecção in vivo a fim de testar a funcionalidade da 5' RNC. A correlação entre variações nas regiões 5' NRC e NS5A e resposta terapêutica, entre os grupos não respondedores e respondedores (NR e R) foram realizadas através de parâmetros de genética molecular. A Energia Livre Mínima (ELM) calculada através do RNAfold sofreu maior influência da posição do que com o número de substituições. Os resultados do RNAshapes mostraram diferenças na probabilidade de predição das shapes, reforçando a idéia de que as substituições alteram a estrutura secundária. Os resultados do RNApdist também mostraram que algumas substituições tem um impacto sobre a predição da estrutura secundária. A heterogeneidade da seqüência da 5' RNC conduziu importantes alterações na eficiência de tradução, implicando que as interações entre o RNA e fatores de tradução podem variar de acordo com o tipo de células. As regiões 5' RNC e NS5A apresentaram baixa variabilidade genética. Apenas a 5' RNC apresentou desvio da neutralidade e significativa variabilidade molecular nos dois grupos estudados (NR e R). A análise filogenética mostrou nenhuma correlação entre variações na seqüência e a. resposta terapêutica

Seroprevalence of hepatitis B and C genotypes among young apparently healthy females of Karachi-Pakistan

Although the prevalence of hepatitis virus infections in Pakistan is still unknown, limited data indicate that the exposure rate to HBV is 35-38% with 4% being carriers and 32% having anti-HBV surface antibodies through natural conversion [1, 2, 3]. Studies in Pakistan have shown that the prevalence rate of HCV is 4.8-14% for, and that it is continuously increasing. Hence there is an urgent need to create awareness about the prevalence of both hepatitis B and C, and to develop preventive measures aimed at minimizing the prevalence of these diseases in the country. Prospective, descriptive study. The study took place from March 2002 till October 2006 at two university campuses in Karachi. A total of 4000 healthy female students were screened for HBs Ag, anti-HBs antibodies and anti-HCV antibodies by rapid immunochromatography, ELISA and PCR. A total of 3820 volunteers [95.5%] were negative by all three methods, 181 [4.5%] tested positive for HB surface antigen and 20 [0.5%] were positive for anti HB surface antibodies; 208 volunteers [5.2%] were positive for HCV. Double infection with HBV and HCV was found in only one patient [0.025%]. Out of 180 HBs antigen positive samples 151 [83.89%] were genotype D, 28 [15.56%] showed mixed infection with genotypes B and D, and one patient [0.56%] showed mixed infection with genotypes C and D. Out of 208 samples positive for HCV antibodies, 107 [51.44%] were genotype 3a, 50 [24.04%] were mix of genotype 3a and 3b, 33 [15.87%] were genotype 3b, 10 [4.81%] were genotype Ib while, 8 [3.84%] samples could not be typed. Although the presence of these pathogenic viruses was not very high in our young healthy female population, it is still a matter of concern to control the unregulated spread of these deadly infections by promoting increased awareness and regular immunization programs in the community. Local manufacturing of vaccines and related products may reduce these infections

Variações nas regiões 5’ não traduzida e na proteína não estrutural NS5A do vírus da Hepatite C em pacientes infectados com o genótipo 1

Embora exibindo considerável variabilidade genética, a região 5' não codificante (5'RNC) do genoma viral é relativamente bem conservada entre todos os genótipos Existem evidências da presença nestes domínios de um sítio de entrada interno do ribossomo (IRES) que permite a tradução cap-independente do RNA viral. A variabilidade na região da proteína não estrutural NS5A, designada “Região Determinante da Suscetibilidade ao interferon” (ISDR), foi associada à resistência ou sensibilidade a terapia com interferon-α. A partir das seqüências obtidas, foram realizadas predições da estrutura secundária da 5' RNC pelos programas RNAfold, RNApdist e RNAshapes. Também foram realizados experimentos de transfecção in vivo a fim de testar a funcionalidade da 5' RNC. A correlação entre variações nas regiões 5' NRC e NS5A e resposta terapêutica, entre os grupos não respondedores e respondedores (NR e R) foram realizadas através de parâmetros de genética molecular. A Energia Livre Mínima (ELM) calculada através do RNAfold sofreu maior influência da posição do que com o número de substituições. Os resultados do RNAshapes mostraram diferenças na probabilidade de predição das shapes, reforçando a idéia de que as substituições alteram a estrutura secundária. Os resultados do RNApdist também mostraram que algumas substituições tem um impacto sobre a predição da estrutura secundária. A heterogeneidade da seqüência da 5' RNC conduziu importantes alterações na eficiência de tradução, implicando que as interações entre o RNA e fatores de tradução podem variar de acordo com o tipo de células. As regiões 5' RNC e NS5A apresentaram baixa variabilidade genética. Apenas a 5' RNC apresentou desvio da neutralidade e significativa variabilidade molecular nos dois grupos estudados (NR e R). A análise filogenética mostrou nenhuma correlação entre variações na seqüência e a. resposta terapêutica

Mannose binding lectin gene haplotype in Iranian patients with hepatitis C infection

Persistent infection with hepatitis C virus [HCV] leads to liver cirrhosis [LC] and often to liverm cancer. Mannose binding lectin [MBL] is a C-type serum lectin, which plays an important role in innate immunity by activating the classical complement pathway. Variants of the MBL have been shown to be associated with low serum concentrations of the protein and to predispose to bacterial, fungal and viral infections. This study was undertaken to investigate the association between polymorphisms of MBL gene and hepatitis C virus infection. We determined genotypes of two promoters and three exon 1 SNPs in mbl2 by SSP-PSR and grouped these genotypes according to related amount of functional MBL production in 100 patients infected with hepatitis C virus and 100 healthy blood donors in Iranian population. MBL gene mutations were determined by means of polymerase chain reaction and restriction fragment length polymorphism analyses. genotypes XA/O or O/O were significantly more frequent among patients infected with hepatitis C virus, where YA/YA genotype was more common among donors. Frequency of alleles X, Y, H and L did not have a significant difference between the two groups as well as alleles HYA, LYA nor LXA. MBL may be one of the factors that influence the course of HCV infection. Additional study on subjects at a high risk for infection with hepatitis C may clarify the role of carriage for the variant allele of mbl2 in a life-long risk of infection

Association of mannose binding lectin polymorphism with hepatitis C infection in northwest of Iran

Persistent infection with hepatitis C virus leads to liver cirrhosis and often to liver cancer. Mannose binding lectin is a C-type serum lectin, which plays an important role in innate immunity by activating the classical complement pathway. Variants of the mannose binding lectin have been shown to be associated with low serum concentrations of the protein and to predispose the subjects to bacterial, fungal and viral infections. This study was undertaken to investigate the association between hepatitis C virus infection and polymorphisms of mannose binding lectin gene. We assessed the single nucleotide polymorphism of mannose binding lectin in exon 1, at codon 52, codon 54 and codon 57 in 100 patients infected with hepatitis C virus and 100 controls in Iranian population. Mannose binding lectin gene mutations were determined by means of polymerase chain reaction and restriction fragment length polymorphism analyses. The occurrence of the codon 54 mutation was significantly higher in patients [OR 3.53, CI 95%: 1.94-6.44, p<0.005]. No significant difference in the frequency of codon 52 and 57 mutations was observed between patient and control groups. Mannose binding lectin may be one of the factors that influence the course of HCV infection. Our results suggest that heterozygous carriage of the variant allele of codon 54 of mannose binding lectin is associated with hepatitis C virus infection in our cases. This may not be true about codons 52 and 57 mutations

Estudo de polimorfismos nos genes das citocinas TGF-ß1, IFN-γ, IL-6, IL-10 e TNF-α em indivíduos portadores da infecção pelo vírus da hepatite c / Study of polymorphism in the genes of the citocinas TGF-ß1, IFN-γ, IL-6, IL-10 e TNF-α it in carrying individuals of the infection for the virus of hepatitis C

As citocinas possuem um papel fundamental na regulação da resposta imunológica. Na infecção causada pelo vírus da hepatite C (VHC), os níveis de produção das citocinas podem interferir na progressão da doença, persistência viral e resposta terapêutica. Os genes de citocinas são polimórficos em sítios específicos, e determinados polimorfismos localizados em regiões codificadoras/regulatórias podem alterar a expressão e a secreção das citocinas. O objetivo deste trabalho foi caracterizar a freqüência de alelos polimórficos nos genes do TNF-α, TGF-ß, IL-10, IL-6, e IFN-γ em pacientes portadores da infecção crônica causada pelo vírus da hepatite C. (...) Estudos complementares de indivíduos expostos ao VHC que conseguiram eliminar o vírus e de pacientes portadores do VHC com avaliação do grau de lesão hepática são necessários para determinar o papel do polimorfismo do gene do TGF-ß (códon 25) na susceptibilidade e no estadiamento/progressão da infecção causada pelo VHC