Cryoglobulinemia in chronic hepatitis C: clinical aspects and response to treatment with interferon alpha and ribavirin

INTRODUCTION: The main extra-hepatic manifestation of hepatitis C is mixed cryoglobulinemia (MC). The aim of this study was to evaluate its prevalence among patients with chronic hepatitis C (CHC), to correlate its presence to host and virological variables and to the response to combined therapy with interferon-alpha and ribavirin. CASUISTIC AND METHODS: 202 CHC naive patients (136 with chronic hepatitis and 66 with cirrhosis) were consecutively evaluated for the presence of cryoglobulins. Cryoprecipitates were characterized by immunoelectrophoresis and classified according to the Brouet's criteria. RESULTS: The prevalence of MC was 27% (54/202), and 24% of them (13/54) showed major clinical manifestation of the disease. Even though type III MC was more frequent (78%), symptomatic MC was more common in type II MC. The presence of cirrhosis (RR = 2.073; IC95% = 1.029 - 4.179; p = 0.041), and age of the patients (RR = 1.035; IC95% = 1.008 - 1.062; p = 0.01) were independently associated with the presence of cryoglobulins. No relationship was found with viral load and genotype. 102 patients were treated with interferon alpha and ribavirin. Among these, 31 had MC. Sustained virological response (around 30%) was similar in patients with and without MC (p = 0.971). CONCLUSION: MC represents a prevalent complication in patients with CHC, specially older and cirrhotic patients. Only 24% of these patients show clinical manifestation of the disease, specially those with type II MC. The presence of MC did not affect the response to therapy.

Sexual transmission of hepatitis C

It is generally agreed that the hepatitis C virus (HCV) can be efficiently transmitted parenterally, although data on viral transmission by sexual or non-sexual intrafamilial contact are conflicting. Since data collection began in 1989, the first study dealt with the risk of sexual transmission among multiple sex partners. Other investigations followed, emphasizing that risk increases in specific groups such as patients co-infected with HIV and HBV, sex workers, homosexuals, illicit drug users and patients attended at sexually transmittable disease clinics. The question arises as to what might be the risk for monogamous heterosexuals in the general population, in which one of the partners has HCV? The literature provides overall rates that vary from zero to 27%; however, most studies affirm that the chances of sexual transmission are low or almost null, with rates for this mode fluctuating from zero to 3%. Intrafamilial transmission is strongly considered but inconclusive, since when mentioning transmission between sex partners within the same household, specific situations also should be considered, such as the sharing of personal hygiene items, like razorblades, toothbrushes, nail clippers and manicure pliers, which are important risk factors in HCV transmission. In this review, we discuss the hypotheses of sexual and/or intrafamilial transmission.

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Trabalho de Projecto apresentado para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Novos Media e Pratica Web

Portal cd4+ and cd8+ t lymphocyte correlate to intensity of interface hepatitis in chronic hepatitis C

BACKGROUND: The pathogenesis of chronic hepatitis C is still a matter of debate. CD4+ and CD8+ T lymphocytes (TL) are typically observed within the portal and periportal spaces of affected livers, but their functional role in hepatitis C progression has not been fully elucidated. METHODS: CD4+ and CD8+ TL were quantified by immunohistochemistry in portal and periportal spaces of 39 liver biopsies from patients with chronic hepatitis C. They were associated to demographic data, histological parameters, laboratory findings of patients and hepatitis C genotypes. RESULTS: There was high numbers of CD4+ and CD8+ TL from which the density of CD4+ T was higher than CD8+ TL in portal and periportal spaces. CD4+ and CD8+ TL were directly correlated to intensity of interface hepatitis. CD8+ TL correlated to serum enzyme levels. CONCLUSION: The high numbers of CD4+ and CD8+ TL in portal and periportal spaces and their correlation to interface hepatitis suggest that hepatitis C evolution depends on the action of intrahepatic T lymphocytes, lending support to the notion of an immune-mediated mechanism in the pathogenesis of chronic hepatitis C.

Desenvolvimento de Frameworks de Testes Automáticos de Software

O objetivo deste trabalho é o desenvolvimento de frameworks de testes automáticos de software. Este tipo de testes normalmente está associado ao modelo evolucionário e às metodologias ágeis de desenvolvimento de software, enquanto que os testes manuais estão relacionados com o modelo em cascata e as metodologias tradicionais. Como tal foi efetuado um estudo comparativo sobre os tipos de metodologias e de testes existentes, para decidir quais os que melhor se adequavam ao projeto e dar resposta à questão "Será que realmente compensa realizar testes (automáticos)?". Finalizado o estudo foram desenvolvidas duas frameworks, a primeira para a implementação de testes funcionais e unitários sem dependências a ser utilizada pelos estagiários curriculares da LabOrders, e a segunda para a implementação de testes unitários com dependências externas de base de dados e serviços, a ser utilizada pelos funcionários da empresa. Nas últimas duas décadas as metodologias ágeis de desenvolvimento de software não pararam de evoluir, no entanto as ferramentas de automação não conseguiram acompanhar este progresso. Muitas áreas não são abrangidas pelos testes e por isso alguns têm de ser feitos manualmente. Posto isto foram criadas várias funcionalidades inovadoras para aumentar a cobertura dos testes e tornar as frameworks o mais intuitivas possível, nomeadamente: 1. Download automático de ficheiros através do Internet Explorer 9 (e versões mais recentes). 2. Análise do conteúdo de ficheiros .pdf (através dos testes). 3. Obtenção de elementos web e respetivos atributos através de código jQuery utilizando a API WebDriver com PHP bindings. 4. Exibição de mensagens de erro personalizadas quando não é possível encontrar um determinado elemento. As frameworks implementadas estão também preparadas para a criação de outros testes (de carga, integração, regressão) que possam vir a ser necessários no futuro. Foram testadas em contexto de trabalho pelos colaboradores e clientes da empresa onde foi realizado o projeto de mestrado e os resultados permitiram concluir que a adoção de uma metodologia de desenvolvimento de software com testes automáticos pode aumentar a produtividade, reduzir as falhas e potenciar o cumprimento de orçamentos e prazos dos projetos das organizações.

Clinical and histological characteristics of HIV and hepatitis C virus-co-infected patients in Brazil: a case series study

Hepatitis C virus (HCV) is an important factor contributing to morbidity and mortality in patients co-infected with HIV and HCV. In addition, liver biopsy is an important tool in the clinical management of these patients. Although liver biopsy is controversial, it is recommended for all patients. Data regarding the clinical and histological characteristics of these patients are scarce not only in Brazil but in Latin America as a whole. With the goal of better understanding these characteristics and the benefit of liver biopsy indications in this disease setting, data collected from 234 patients followed from 1996 to 2004 at Casa da AIDS, São Paulo, were analyzed. The following variables were extracted from the patients' medical files at the time of liver biopsy: sex, age, hepatitis C infection risk factors, hepatitis C infection duration, ALT levels, CD4+ T cell counts, history of alcohol abuse, history of antiretroviral therapy, HCV genotype, and liver histological alterations. CONCLUSIONS: 1 - Hepatitis C virus 1 and 3 were the most frequently identified genotypes and were diagnosed in 72% and 25.5% of cases respectively; 2 - Structural liver alterations were found to be mild or absent in 48.2% (113/234) of the analyzed patients; 3 - Fifty-three patients (23%) had normal ALT levels and 4 - Significant liver architectural changes (F2-F3) were evident in 22.5% of the patients with normal ALT levels.

Candida bloodstream infection: data from a teaching hospital in Mato Grosso do Sul, Brazil

The incidence of Candida bloodstream infection has increased over the past years. In the Center-West region of Brazil, data on candidemia are scarce. This paper reports a retrospective analysis of 96 cases of Candida bloodstream infection at a Brazilian tertiary-care teaching hospital in the state of Mato Grosso do Sul, from January 1998 to December 2006. Demographic, clinical and laboratory data were collected from medical records and from the hospital's laboratory database. Patients' ages ranged from three days to 92 years, with 53 (55.2%) adults and 43 (44.8%) children. Of the latter, 25 (58.1%) were newborns. The risk conditions most often found were: long period of hospitalization, utilization of venous central catheter, and previous use of antibiotics. Fifty-eight (60.4%) patients died during the hospitalization period and eight (13.7%) of them died 30 days after the diagnosis of candidemia. Candida albicans (45.8%) was the most prevalent species, followed by C. parapsilosis (34.4%), C. tropicalis (14.6%) and C. glabrata (5.2%). This is the first report of Candida bloodstream infection in the state of Mato Grosso do Sul and it highlights the importance of considering the possibility of invasive Candida infection in patients exposed to risk factors, particularly among neonates and the elderly.

Prevalence of hepatitis C virus infection in quilombo remnant communities in Central Brazil

In order to determine the prevalence of hepatitis C virus (HCV) infection in quilombo remnant communities in Central Brazil, 1,007 subjects were interviewed in all 12 communities existing in Mato Grosso do Sul State, Central Brazil. Blood samples were collected and sera were tested for anti-HCV by enzyme-linked immunosorbent assay. Positive samples were retested for confirmation using a line immunoassay and were also subjected to HCV RNA detection. The prevalence of HCV infection was 0.2%. This finding shows a low prevalence of HCV infection in quilombo remnant communities in Central Brazil.

Influence of human t-cell lymphotropic virus type 1 (HTLV-1) Infection on laboratory parameters of patients with chronic hepatitis C virus

Hepatitis C virus (HCV) and human T-cell lymphotropic virus type 1 (HTLV-1) share routes of transmission and some individuals have dual infection. Although some studies point to a worse prognosis of hepatitis C virus in patients co-infected with HTLV-1, the interaction between these two infections is poorly understood. This study evaluated the influence of HTLV-1 infection on laboratory parameters in chronic HCV patients. Twelve HTLV-1/HCV-coinfected patients were compared to 23 patients infected only with HCV, in regard to demographic data, risk factors for viral acquisition, HCV genotype, presence of cirrhosis, T CD4+ and CD8+ cell counts and liver function tests. There was no difference in regard to age, gender, alcohol consumption, smoking habits, HCV genotype or presence of cirrhosis between the groups. Intravenous drug use was the most common risk factor among individuals co-infected with HTLV-1. These patients showed higher TCD8+ counts (p = 0.0159) and significantly lower median values of AST and ALT (p = 0.0437 and 0.0159, respectively). In conclusion, we have shown that HCV/HTLV-1 co-infected patients differs in laboratorial parameters involving both liver and immunological patterns. The meaning of these interactions in the natural history of these infections is a matter that deserves further studies.

Chronic hepatitis C: hepatic iron content does not correlate with response to antiviral therapy

The complex interaction between hepatitis C virus infection, iron homeostasis and the response to antiviral treatment remains controversial. The aim of this study was to evaluate the influence of hepatic iron concentration (HIC) on the sustained virological response (SVR) to antiviral therapy in patients with chronic hepatitis C. A total of 50 patients who underwent pretreatment liver biopsy with assessment of HIC by graphite furnace atomic absorption spectroscopy and were subsequently submitted to antiviral treatment with interferon/peginterferon and ribavirin were included in the study. Patients with alcoholism, history of multiple blood transfusion, chronic kidney disease, hemolytic anemia and parenteral iron therapy were excluded. The iron related markers and HIC were compared between those who achieved an SVR and non-responders (NR) patients. The mean age was 45.7 years and the proportion of patients' gender was not different between SVR and NR patients. The median serum iron was 138 and 134 µg/dL (p = 0.9), the median serum ferritin was 152.5 and 179.5 ng/mL (p = 0.87) and the median HIC was 9.9 and 8.2 µmol/g dry tissue (p = 0.51), for SVR and NR patients, respectively. Thus, hepatic iron concentration, determined by a reliable quantitative method, was not a negative predictive factor of SVR in patients with chronic hepatitis C presenting mild to moderate hepatic iron accumulation.

Hepatitis C virus genotypes in hemodialysis patients in the Federal District, Brazil

Hepatitis C virus (HCV) genotypes and subtypes were determined in hemodialysis patients in the Federal District, Brazil, by sequencing of the 5' noncoding (NC) and nonstructural 5B (NS5B) regions. From 761 patients, 66 anti-HCV-positive samples were tested for HCV RNA. All 51 HCV RNA-positive samples by PCR of the 5' NC region were genotyped as genotypes 1 (90.2%) and 3 (9.8%). Subtype 1a (82.3%) was the most prevalent, followed by subtypes 3a (9.8%), 1b (5.9%) and 1a/1b (2.0%). Forty-two samples could be amplified and genotyped in the NS5B region: 38 (90.5%) as genotype 1, subtypes 1a, and 8 (9.5%) as genotype 3, subtype 3a. For the 42 samples sequenced in both regions, the genotypes and subtypes determined were concordant in 100% and 95.2% of cases, respectively. Two samples presented discrepant results, with the 5' NC region not distinguishing correctly the subtypes 1a and 1b. These findings indicate that the HCV genotype 1, subtype 1a, is the most prevalent among hemodialysis patients in the Federal District, Brazil.

SHõWA: A Self-healing Framework for Web-based Applications

The complexity of systems is considered an obstacle to the progress of the IT industry. Autonomic computing is presented as the alternative to cope with the growing complexity. It is a holistic approach, in which the systems are able to configure, heal, optimize, and protect by themselves. Web-based applications are an example of systems where the complexity is high. The number of components, their interoperability, and workload variations are factors that may lead to performance failures or unavailability scenarios. The occurrence of these scenarios affects the revenue and reputation of businesses that rely on these types of applications. In this article, we present a self-healing framework for Web-based applications (SHõWA). SHõWA is composed by several modules, which monitor the application, analyze the data to detect and pinpoint anomalies, and execute recovery actions autonomously. The monitoring is done by a small aspect-oriented programming agent. This agent does not require changes to the application source code and includes adaptive and selective algorithms to regulate the level of monitoring. The anomalies are detected and pinpointed by means of statistical correlation. The data analysis detects changes in the server response time and analyzes if those changes are correlated with the workload or are due to a performance anomaly. In the presence of per- formance anomalies, the data analysis pinpoints the anomaly. Upon the pinpointing of anomalies, SHõWA executes a recovery procedure. We also present a study about the detection and localization of anomalies, the accuracy of the data analysis, and the performance impact induced by SHõWA. Two benchmarking applications, exercised through dynamic workloads, and different types of anomaly were considered in the study. The results reveal that (1) the capacity of SHõWA to detect and pinpoint anomalies while the number of end users affected is low; (2) SHõWA was able to detect anomalies without raising any false alarm; and (3) SHõWA does not induce a significant performance overhead (throughput was affected in less than 1%, and the response time delay was no more than 2 milliseconds).

Seroprevalence of hepatitis B and C infection markers among children and adolescents in the southern Brazilian region

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections account for a substantial proportion of liver diseases worldwide. The aim of this study was to determine the prevalence of HBV and HCV serological markers among children and adolescents and verify the epidemiology of the HBV infection over than a decade of the introduction of vaccination program. Serologic markers to HBsAg, total anti-HBc and anti-HCV had been tested in 393 samples. The seropositivity for HBsAg was 0.76% and for total anti-HBc was 1.02%. Copositivity between HBsAg and total anti-HBc was verified in 0.76% of the analyzed samples. There was no seropositivity for anti-HCV marker. The seroprevalence of HBV infection markers among children and adolescents in the southern Brazilian region is high compared to that reported in other countries. Preventive measures, such as educational activities in addition to the universal childhood HBV vaccination, should be initiated in order to reduce the morbimortality and the economic burden associated with the disease.

In vitro and in vivo antileishmanial efficacy of a combination therapy of diminazene and artesunate against Leishmania donovani in BALB/c mice

The in vitro and in vivo activity of diminazene (Dim), artesunate (Art) and combination of Dim and Art (Dim-Art) against Leishmania donovani was compared to reference drug; amphotericin B. IC50 of Dim-Art was found to be 2.28 ± 0.24 µg/mL while those of Dim and Art were 9.16 ± 0.3 µg/mL and 4.64 ± 0.48 µg/mL respectively. The IC50 for Amphot B was 0.16 ± 0.32 µg/mL against stationary-phase promastigotes. In vivo evaluation in the L. donovani BALB/c mice model indicated that treatments with the combined drug therapy at doses of 12.5 mg/kg for 28 consecutive days significantly (p < 0.001) reduced parasite burden in the spleen as compared to the single drug treatments given at the same dosages. Although parasite burden was slightly lower (p < 0.05) in the Amphot B group than in the Dim-Art treatment group, the present study demonstrates the positive advantage and the potential use of the combined therapy of Dim-Art over the constituent drugs, Dim or Art when used alone. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.