Hepcidin: Homeostasis and Diseases Related to Iron Metabolism.

Iron is an essential metal for cell survival that is regulated by the peptide hormone hepcidin. However, its influence on certain diseases is directly related to iron metabolism or secondary to underlying diseases. Genetic alterations influence the serum hepcidin concentration, which can lead to an iron overload in tissues, as observed in haemochromatosis, in which serum hepcidin or defective hepcidin synthesis is observed. Another genetic imbalance of iron is iron-refractory anaemia, in which serum concentrations of hepcidin are increased, precluding the flow and efflux of extra- and intracellular iron. During the pathogenesis of certain diseases, the resulting oxidative stress, as well as the increase in inflammatory cytokines, influences the transcription of the HAMP gene to generate a secondary anaemia due to the increase in the serum concentration of hepcidin. To date, there is no available drug to inhibit or enhance hepcidin transcription, mostly due to the cytotoxicity described in the in vitro models. The proposed therapeutic targets are still in the early stages of clinical trials. Some candidates are promising, such as heparin derivatives and minihepcidins. This review describes the main pathways of systemic and genetic regulation of hepcidin, as well as its influence on the disorders related to iron metabolism.

High prevalence of hepatitis E virus antibodies among blood donors in Southern Brazil.

Brazil has been classified as moderately endemic for hepatitis E virus (HEV) infection. However, data on the seroprevalence of HEV in this region are limited. This study evaluated the prevalence of past or present HEV infection among blood donors in the metropolitan area of Itajai Valley, Southern Brazil, a region of predominant German heritage, where cultural habits result in a high consumption of pork. Serum samples from 300 blood donors were tested in December 2014 using serological and molecular methods. Anti-HEV IgG antibodies were detected in 30 (10%) subjects, and categorized age groups revealed an age-dependent increase of HEV seroprevalence. Only one subject had anti-HEV IgM, whereas none tested positive for HEV-RNA. The present data demonstrate a higher seroprevalence of anti-HEV IgG in blood donors than previously reported in Brazil.

Immune memory response induced in vitro by recombinant hepatitis B surface antigen challenge 13-18 years after primary vaccination.

The question of whether booster doses are required to maintain long-term protection against hepatitis B virus (HBV) after primary vaccination remains to be determined. Thus, the aim of this study was to evaluate the immune memory responses to hepatitis B surface antigen (HBsAg) challenge in vaccinated individuals through an in vitro-specific stimulation assay. Peripheral blood mononuclear cells (4 × 10(6) cells/ml) were stimulated with 50 ng/ml of recombinant HBsAg. In vitro anamnestic antibody responses, as shown by detection of high avidity antibody in culture supernatants, were found 13-18 years after primary vaccination and were not correlated with serum antibodies (r = -0.177; P = 0.377). In addition, the findings from this study indicate that immune memory against hepatitis B was well preserved in 40.0% and 60.0% of vaccinees with anti-HBs levels less than 10 IU/L or lacking serum antibodies altogether, respectively. In conclusion, the data suggest the presence of immunological memory in vaccinated individuals, including those who showed anti-HBs <10 IU/L or undetectable antibody.

Hepatitis C worldwide and in Brazil: silent epidemic--data on disease including incidence, transmission, prevention, and treatment.

Hepatitis C virus (HCV) is endemic worldwide and according to the World Health Organization (WHO), there are about 150 million chronic carriers worldwide. The infection is a leading cause of liver diseases like cirrhosis and hepatocellular carcinoma (HCC); thus, HCV infection constitutes a critical public health problem. There are increasing efforts worldwide in order to reduce the global impact of hepatitis C through the implementation of programmatic actions that may increase the awareness of viral hepatitis and also improve surveillance, prevention, and treatment. In Brazil, about 1,5 million people have been chronically infected with HCV. The country has a vast territory with uneven population density, and hepatitis C incidence rates are variable with the majority of cases concentrated in the most populated areas. Currently, the main priorities of Brazilian Ministry of Health's strategies for viral hepatitis management include the prevention and early diagnosis of viral hepatitis infections; strengthening of the healthcare network and lines of treatment for sexually transmitted diseases, viral hepatitis, and AIDS; improvement and development of surveillance, information, and research; and promotion of universal access to medication. This review aims to summarize the available data on hepatitis C epidemiology and current status of efforts in prevention and infection control around the world and in Brazil.

Serum levels of IgG antibodies against oxidized LDL and atherogenic indices in HIV-1-infected patients treated with protease inhibitors.

BACKGROUND: Antibodies against low-density lipoproteins (LDLs) that have been oxidized are associated with development of atherosclerotic lesions. In individuals infected with human immunodeficiency virus type 1 (HIV-1) with or without therapy, dyslipidemia and increased cardiovascular risk are observed. METHODS: Serum levels of IgG antibodies against oxidized LDLs (IgG anti-oxLDL Abs) were determined by assay in 151 HIV-1-infected patients. Of these, 42 patients did not receive anti-retroviral therapy (ART-naïve), whereas 109 received highly active anti-retroviral therapy (HAART) consisting of lopinavir/ritonavir (LOP/r; n=50), efavirenz (EFV; n=30) and nevirapine (NVP; n=29) associated with nucleoside reverse transcriptase inhibitors. HIV-1 seronegative individuals (n=43) participated in the study. The following parameters were quantified: total cholesterol and its fractions, atherogenic indices (AIs), apolipoproteins A1 and B100, high sensitivity C-reactive protein, CD4+ and CD8+ T cells, and HIV-1-RNA. RESULTS: Levels of IgG anti-oxLDL Abs were significantly higher (p<0.05) in the LOP/r group compared with the EFV and/or NVP and the seronegative group: median 0.32 (0.15, 0.58; 95% confidence interval) vs. 0.25 (0.13, 0.53) vs. 0.18 (0.04, 0.38), respectively. HIV-1-infected ART-naïve patients (n=42) presented antibodies levels similar to those observed for the LOP/r group, 0.33 (0.13, 0.63; p>0.05). The levels of IgG anti-oxLDL Abs correlated with an increase in AIs (r=0.216; p=0.036) and triglycerides (r=0.220; p=0.044) in the LOP/r group, and AIs in the ART-naïve group (r=0.300; p=0.046). CONCLUSIONS: Patients treated with LOP/r showed higher levels of IgG anti-oxLDL Abs compared with patients treated with EFV or NVP regimens, and these levels were associated with an increase in AIs.

An overview of the mechanisms of HIV-related thrombocytopenia.

The first thrombocytopenia cases related to the human immunodeficiency virus (HIV) were described even before its isolation in 1983. Subsequently, multiple mechanisms have been proposed to elucidate the etiology of thrombocytopenia. In addition to other types of cytopenia affecting patients with HIV, thrombocytopenia is observed in about 10-50% HIV patients as one of the first clinical signs of infection. Thus, in this review we aim to summarize the mechanisms proposed for thrombocytopenia since the discovery of HIV, and especially the innovations in the field in recent years. Among the different mechanisms suggested for HIV-related thrombocytopenia, there is emphasis on the accelerated destruction of platelets (PLTs) due to the action of immune complexes, and the presence of anti-PLT and anti-HIV antibodies that cross-react with the PLT membrane. There are also secondary causes of thrombocytopenia, such as the effect of drugs and opportunistic diseases associated with HIV.

Prevalence of HCV infection in a prison population of the greater Florianópolis area.

INTRODUCTION: The present study aimed to estimate the prevalence of Hepatitis C virus (HCV) infection in a prison population. METHODS: A total of 147 individuals were interviewed and subjected to venipuncture for collection of blood sample. The study population consisted of male individuals who attended the health unit of the state penitentiary of Florianópolis. RESULTS: The prevalence of HCV infection was 5.4%. Regarding behavioral variables, 95 (64.6%, p<0.0507) subjects reported consuming alcohol and 7 (4.8%, p<0.0476) reported having already used injectable drugs. CONCLUSIONS: The prevalence of HCV infection in the studied population was higher than that in the general populations.

Alterations in lipid transfer to high-density lipoprotein (HDL) and activity of paraoxonase-1 in HIV+ patients.

HIV+ patients often develop alterations of the plasma lipids that may implicate in development of premature coronary artery disease. High-density lipoprotein (HDL) has an important role in preventing atherogenesis and the aim of this study was to investigate aspects of HDL function in HIV+ patients. HIV+ patients (n = 48) and healthy control subjects (n = 45) of both sexes with similar age were studied. Twenty-five were not being treated with antiretroviral agents, 13 were under reverse transcriptase inhibitor nucleosidic and non-nucleosidic (NRTI+NNRTI) and 10 were under NRTI + protease inhibitors (NRTI+PI) treatment. Paraoxonase 1 (PON1) activity and the transfer of free and esterified cholesterol, tryglicerides and phospholipids from a lipidic nanoemulsion to HDL were analyzed. In comparison with healthy controls, HIV+ patients presented low PON-1 activity and diminished transfer of free cholesterol and tryglicerides. In contrast, phospholipid transfer was increased in those patients, whereas the transfer of cholesteryl esters was unchanged. NRTI+NNRTI increases the transfer of cholesteryl esters and triglycerides but in NRTI+PI there was no difference in respect to non-treated HIV+ patients. HDL from HIV+ patients has smaller antioxidant properties, as shown by lower PON-1 activity, and the transfer of lipids to this lipoprotein fraction is also altered, suggesting that HDL function is defective in those patients.

Prevalence of human immunodeficiency virus infection and associated risk factors among prison inmates in the City of Florianópolis.

INTRODUCTION: This study aimed to estimate the prevalence of human immunodeficiency virus (HIV) infection among prison inmates and to define the behavioral profile of infected individuals. METHODS:: In total, 147 individuals were interviewed and provided biological material. The study population consisted of male individuals who presented at the health unit of the Florianopolis State Penitentiary. RESULTS:: The prevalence of HIV infection was 2.1% (95% confidence interval, 0.4-5.8). With respect to the behavioral profile of individuals, no variable showed statistical significance. CONCLUSIONS:: The prevalence of HIV infection among prison inmates was higher than that reported for the general population.

Estimation of the residual risk for the transmission of HIV in blood donors from the mountain region of Santa Catarina.

The HIV, in hemotheraphy, may be transmitted by erythrocyte, platelets, crioprecipitated, frozen fresh plasma and possibly, by other blood components. Appropriate legislations for this new reality were elaborated normatizing the hemotheraphy practices in Brazil, creating a set of procedures and actions aiming at guaranteeing the quality of the blood, during the whole process. However, the residual risk remains, and it can be calculated as a product of the incidence and period of the immunological window. The objective [corrected] of the present study was to determine the rate of residual risk of the HIV blood transmission, in the blood donors from the Mountain Region of Santa Catarina. In order to calculate the residual risk of the HIV markers, 4,857 donors of repetition from the 24,969 individuals who donated blood from 2000 to 2003 were evaluated, and the results showed a serumconversion, in one case. The method used to calculate the residual risk followed the model of the immunological incidence window used by Schreiber (1996), in the USA. A estimate risk of 1:50,000 was verified. The case was considered as confirmed when one of the HIV, in the Hemocenter, is considered one of the HIV markers, in 1:50.000, which confirms the hypothesis that the new legislation related to the Blood National Politics, with the introduction of more sensible tests is decreasing the immunological window, diminishing the residual and, consequently, intensifying the transfusion security.

Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs.

For human immunodeficiency virus (HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy (HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results.

Vaccination coverage and immunity against hepatitis B among HIV-infected patients in South Brazil.

Evidence-based strategies to improve the hepatitis B virus (HBV) vaccination coverage rates might help to reduce the burden caused by co-infection with HBV and human immunodeficiency virus (HIV). In this study, the aim was to evaluate the vaccination coverage and immunity against HBV among HIV-infected individuals in South Brazil, and identify factors that are associated with compliance patterns and antibody reactivity. Three hundred HIV-infected men and women were included in this survey. The patients answered a standardized questionnaire, and vaccination cards were checked in order to assess hepatitis B vaccine status. A blood sample was collected for quantitative determination of antibody to hepatitis B virus surface antigen (anti-HBs). Participants were also evaluated for their CD4 cell count and HIV viral load. The overall vaccination coverage of HBV vaccination found in this study (57.4%) was lower than that was previously reported in South Brazil. Anti-HBs levels >10IU/L were observed in 47.0% of the studied population. A significant inequality in the coverage rates and antibody reactivity was found in favor of patients with better economic status. In conclusion, the results indicate the need for improvement in the HBV vaccination coverage among HIV carriers, in particular focusing on low-income individuals.

Seroprevalence of HbsAg, Anti-HBc and anti-HCV in Southern Brazil, 1999-2001.

The prevalence of infection by the hepatitis B (HBV) and C (HCV) viruses varies among geographical regions. We evaluated 263,795 blood donor samples collected from 1999-2001 in various cities in the state of Santa Catarina to determine the prevalence of HbsAg, anti-HBc and anti-HCV markers. The markers were analyzed by immunoenzymatic tests, as determined by the Ministry of Health, and the data were obtained from blood banks and from ANVISA (the Brazilian National Agency for Sanitary Vigilance). There was a significant reduction in the mean frequency of HbsAg and anti-HBc during the study period, from 0.98% to 0.64% and from 8.83% to 5.35%, respectively, though they varied considerably among the different regions. There was also a decrease in the mean frequency of anti-HCV, although it was not significant, decreasing from 0.38% to 0.34%. Even with this reduction, the frequency of these markers was still high compared with that found in other countries, indicating high rates of infection by hepatitis B and C viruses. This emphasizes the urgency of vaccination programs against HBV, especially in some regions of Santa Catarina state, in order to reduce the prevalence of this infection and consequently reduce the risk of transmission through sexual relations or from the donation of blood and/or hemocomponents.

Effect of N-acetyl-L-cysteine on lymphocyte apoptosis, lymphocyte viability, TNF-alpha and IL-8 in HIV-infected patients undergoing anti-retroviral treatment.

N-acetyl-L-cysteine (NAC) has been proposed as an additional therapeutic agent for AIDS patients because it reduces human immunodeficiency virus type 1 (HIV-1) replication in stimulated CD4+ lymphocytes, and it ameliorates immunological reactivity. In a randomized, 180-day, double-blind, placebo-controlled trial performed with HIV-infected patients classified as A2 and A3 according to the criteria of the Center for Disease Control and Prevention, we investigated the effects of oral administration of NAC on HIV-infected patients undergoing their first anti-retroviral therapy; viral load, CD4+ lymphocyte, lymphocyte viability and apoptosis, and TNF-alpha and IL-8 levels were determined. Sixteen patients who received anti-retroviral therapy plus a placebo formed the control group and the study group consisted of 14 patients who received anti-retroviral therapy and NAC supplementation. A significant decrease was seen in viral load, TNF-alpha and IL-8 levels, and lymphocyte apoptosis, and a significant increase was found in levels of CD4+ lymphocytes and lymphocyte viability in both groups after anti-retroviral treatment, but no measurable benefits of anti-retroviral therapy plus NAC oral supplementation (600 mg/day) were found in relation to anti-retroviral therapy alone, and the baseline levels of cysteine and glutathione in plasma were not recovered by this treatment. In conclusion, the daily doses of NAC necessary for the total recuperation of plasma cysteine and glutathione levels in HIV-infected patients and the additional benefits following the supplementation of NAC in patients submitted to anti-retroviral therapy, need to be studied further.

Prevalence of HCV infection in a prison population of the greater Florianópolis area

Abstract INTRODUCTION The present study aimed to estimate the prevalence of Hepatitis C virus (HCV) infection in a prison population. METHODS: A total of 147 individuals were interviewed and subjected to venipuncture for collection of blood sample. The study population consisted of male individuals who attended the health unit of the state penitentiary of Florianópolis. RESULTS: The prevalence of HCV infection was 5.4%. Regarding behavioral variables, 95 (64.6%, p<0.0507) subjects reported consuming alcohol and 7 (4.8%, p<0.0476) reported having already used injectable drugs. CONCLUSIONS: The prevalence of HCV infection in the studied population was higher than that in the general populations.

Human paraoxonase-1 activity is related to the number of CD4+ T-cells and is restored by antiretroviral therapy in HIV-1-infected individuals.

BACKGROUND: Paraoxonase-1 (PON1) activity is suggested to be altered in individuals infected with human immunodeficiency virus type-1 (HIV-1). We investigated PON1 activity in individuals receiving different regimens of highly active antiretroviral therapy (HAART). METHODS: PON1 activity was evaluated in 91 HIV-1 seronegative and 624 HIV-1 infected individuals (115 were not undergoing therapy (ART-naïve), and 509 were receiving HAART). HIV-1 infected individuals were treated with the following: efavirenz (EFV; n = 195) or nevirapine (NVP; n = 95) or lopinavir/ritonavir (LOP/r; n = 219). Serum levels of total cholesterol (TC), HDL, and low-density lipoprotein (LDL) fractions and the atherogenic indices (AI, TC : HDL, and LDL : HDL ratios) were determined. RESULTS: PON1 activity (U/L) was lower in the ART-naïve group compared with the other groups. PON1 activity correlated with CD4+ T-cell number of ART-naïve group (r = 0,121; P = 0,014). The LOP/r group showed a reduction in HDL and an increase in AI (TC : HDL ratio) in comparison with other groups. CONCLUSION: PON1 activity was reduced in untreated individuals, but not in individuals receiving HAART. PON1 activity correlated with the number of CD4+ T-cells. The findings suggest that the activity of PON1 is associated with the immune status of HIV-1 infected individuals.

The prevalence of hepatitis B virus infection markers and socio-demographic risk factors in HIV-infected patients in Southern Brazil.

INTRODUCTION: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections are two of the world's most important infectious diseases. Our objective was to determine the hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) prevalences among adult HIV-infected patients and identify the associations between socio-demographic variables and these HBV infection markers. METHODS: This study was performed from October 2012 to March 2013. Three hundred HIV-seropositive patients were monitored by the Clinical Analysis Laboratory of Professor Polydoro Ernani de São Thiago University Hospital, Santa Catarina, Brazil. The blood tests included HBsAg, anti-HBc immunoglobulin M (IgM) and total anti-HBc. Patients reported their HIV viral loads and CD4+ T-cell counts using a questionnaire designed to collect sociodemographic data. RESULTS: The mean patient age was 44.6 years, the mean CD4 T-cell count was 525/mm3, the mean time since beginning antiretroviral therapy was 7.6 years, and the mean time since HIV diagnosis was 9.6 years. The overall prevalences of HBsAg and total anti-HBc were 2.3% and 29.3%, respectively. Among the individuals analyzed, 0.3% were positive for HBsAg, 27.3% were positive for total anti-HBc, and 2.0% were positive either for HBsAg or total anti-HBc and were classified as chronically HBV-infected. Furthermore, 70.3% of the patients were classified as never having been infected. Male gender, age >40 years and Caucasian ethnicity were associated with an anti-HBc positive test. CONCLUSIONS: The results showed an intermediate prevalence of HBsAg among the studied patients. Moreover, the associations between the anti-HBc marker and socio-demographic factors suggest a need for HBV immunization among these HIV-positive individuals, who are likely to have HIV/HBV coinfection.

In vitro lymphocyte stimulation by recombinant hepatitis B surface antigen: a tool to detect the persistence of cellular immunity after vaccination.

The study of the human immune response to hepatitis B virus (HBV) has been hampered by the lack of an adequate model to evaluate the hepatitis B surface antigen (HBsAg) specific cell response. Thus, this study was conducted to perform an in vitro analysis of the antigenic properties of recombinant HBsAg and demonstrate the influence of variables such as culture time, antigen concentration and cell density on lymphocyte proliferation. Peripheral blood mononuclear cells (PBMCs) were isolated from the venous blood of vaccinated individuals, and in vitro cellular immune responses were evaluated using an HBsAg-specific proliferation assay. Lymphoproliferative responses were detected in culture systems, despite the lack of serum antibodies. Optimal results were obtained when lymphocytes were stimulated at a seeding density of 4×10(6) cells/mL, with 50 ng/mL of recombinant HBsAg protein vaccine for 3 days. Data from the present study may contribute to the development of an adequate system to evaluate the cellular immune responses to HBsAg in vaccine recipients.

Comprometimento hemostático em pacientes com icterícia obstrutiva / Haemostatic impairment in patients with obstructive jaundice

A doença hepática é associada à alterações hemostáticas devido à diminuição na síntese dos fatores de coagulação. Neste sentido, objetivou-se avaliar o comprometimento da hemostasia em pacientes com icterícia obstrutiva. Os pacientes foram analisados por gênero, idade, etiologia da doença, tempo de protrombina (TP) e tempo de tromboplastina parcial (TTP) antes e após a cirurgia. A icterícia obstrutiva ocorreu com maior frequência entre as mulheres (60,0%), sendo a coledocolitíase a causa mais comum da doença (80,0%). Os valores pré-cirúrgicos do TTP estavam dentro da faixa normal. No entanto, todos os pacientes apresentaram um TP prolongado na avaliação pré-operatória. Uma redução significativa (p<0,001) foi verificada na análise pós-operatória do TP, atingindo a faixa normal em 66,7% dos pacientes estudados. Verificou-se uma correlação positiva (r = 0,813 p<0,001) entre os valores pré-operatórios do TP e a idade dos pacientes. Além disso, os valores pré-operatórios e pós-operatórios do TP foram significativamente mais elevados (p<0,05) entre pacientes com icterícia obstrutiva de etiologia tumoral. Os resultados deste estudo demonstraram uma forte correlação entre a idade dos pacientes e a atividade dos fatores de coagulação vitamina K dependentes, além de uma diminuição significativa na atividade destes fatores em pacientes com icterícia obstrutiva de etiologia tumoral.

Liver disease is associated with haemostatic abnormalities due to the decreased synthesis of the clotting factors. Therefore, this study aimed to evaluate the impairment of haemostasis in patients with obstructive jaundice. Patients were analyzed by gender, age, cause of jaundice, prothrombin time (PT) and partial thromboplastin time (PTT) before and after surgery. Obstructive jaundice occurred more commonly amongst the females (60.0%), and choledocholithiasis was the most frequent cause of the disease (80.0%). Presurgical PTT values were within the normal range, whereas all the patients showed increased PT in the preoperative evaluation. A significant decrease (p<0.001) was found in the postoperative PT measurement, reaching the normal range in 66.7% of the studied patients. A positive correlation was found between the preoperative PT values and the age of the patients (r = 0.813 p<0.001). In addition, preoperative and postoperative PT values were significantly higher (p<0.05) among the patients with obstructive jaundice of tumoral etiology. Results from this study have shown that activity of vitamin K-dependent clotting factors in obstructive jaundice was strongly correlated with subject's age and was significantly decreased in patients with tumoral etiology.

Hepatitis B immunity and vaccination coverage among young adult males in the Air Force in South Brazil.

We conducted a cross-sectional seroprevalence study to determine hepatitis B vaccination coverage and hepatitis B virus (HBV) immunity in a population of young adult males. Specifically, the population is comprised of Air Force conscripts from the metropolitan region of Florianópolis, Santa Catarina, South Brazil, who were born prior to the full implementation of the HBV vaccination program. Of the 371 young males surveyed, 90% received at least 1 dose of the vaccine and 84% completed the 3-dose schedule. Overall, 57% had positive anti-HBs titers. We must continue to vaccinate individuals up to 20 years of age in order to guarantee a significant reduction in cases of hepatitis B virus.