Quoi de neuf pour le traitement de l'hépatite B [What's new in the treatment of hepatitis B infection?]

Although the number of available antiviral drugs for hepatitis B infection (VHB) today is higher than ever, treatment of chronic VHB infection is still often managed by specialists because of the complex natural history of this viral infection and of the risk of selecting viral strains that are resistant to therapy. Different clinical and virological aspects need to be considered to establish a correct indication for therapy. Once antiviral therapy has been started, patients need close monitoring to guarantee adequate compliance and to detect promptly the selection of viral variants resisting to therapy.

A possible correlation between the host genetic background in the epidemiology of Hepatitis B virus in the Amazon region of Brazil

The Amazon region of Brazil is an area of great interest because of the large distribution of hepatitis B virus in specific Western areas. Seven urban communities and 24 Indian groups were visited in a total of 4,244 persons. Each individual was interviewed in order to obtain demographic and familial information. Whole blood was collected for serology and genetic determinations. Eleven genetic markers and three HBV markers were tested. Among the most relevant results it was possible to show that (i) there was a large variation of previous exposure to HBV in both urban and non-urban groups ranging from 0 to 59.2%; (ii) there was a different pattern of epidemiological distribution of HBV that was present even among a same linguistic Indian group, with mixed patterns of correlation between HBsAg and anti-HBs and (iii) the prevalence of HBV markers (HBsAg and anti-HBs) were significantly higher (P=0.0001) among the Indian population (18.8%) than the urban groups (12.5%). Its possible that the host genetic background could influence and modulate the replication of the virus in order to generate HB carrier state.

A randomized trial of amphotericin B alone or in combination with itraconazole in the treatment of mucocutaneous leishmaniasis

A randomized trial of amphotericin B (AB) alone and in combination with oral itraconazole (IZ) is carried out in two groups of 10 mucocutaneous leishmaniasis patients from Bolivia and Peru. AB+IZ combination is no better than AB monotherapy, as far as efficacy and tolerability are concerned. No antagonism was detected.

Voriconazole-Induced Inhibition of the Fungicidal Activity of Amphotericin B in Candida Strains with Reduced Susceptibility to Voriconazole: an Effect Not Predicted by the MIC Value Alone.

An antagonistic effect of voriconazole on the fungicidal activity of sequential doses of amphotericin B has previously been demonstrated in Candida albicans strains susceptible to voriconazole. Because treatment failure and the need to switch to other antifungals are expected to occur more often in infections that are caused by resistant strains, it was of interest to study whether the antagonistic effect was still seen in Candida strains with reduced susceptibility to voriconazole. With the hypothesis that antagonism will not occur in voriconazole-resistant strains, C. albicans strains with characterized mechanisms of resistance against voriconazole, as well as Candida glabrata and Candida krusei strains with differences in their degrees of susceptibility to voriconazole were exposed to voriconazole or amphotericin B alone, to both drugs simultaneously, or to voriconazole followed by amphotericin B in an in vitro kinetic model. Amphotericin B administered alone or simultaneously with voriconazole resulted in fungicidal activity. When amphotericin B was administered after voriconazole, its activity was reduced (median reduction, 61%; range, 9 to 94%). Levels of voriconazole-dependent inhibition of amphotericin B activity differed significantly among the strains but were not correlated with the MIC values (correlation coefficient, -0.19; P = 0.65). Inhibition was found in C. albicans strains with increases in CDR1 and CDR2 expression but not in the strain with an increase in MDR1 expression. In summary, decreased susceptibility to voriconazole does not abolish voriconazole-dependent inhibition of the fungicidal activity of amphotericin B in voriconazole-resistant Candida strains. The degree of interaction could not be predicted by the MIC value alone.

Chronic carriers of hepatitis B surface antigen in an endemic area for schistosomiasis mansoni in Brazil

Data on the association of schistosomiasis and hepatitis B in field-based studies are scarce. Two areas have been selected for this study: i) Queixadinha, endemic for schistosomiasis, with a population of 693 individuals, and ii) Capão, a control non-endemic area, with 515 inhabitants. Sera of all individuals in both areas were tested for hepatitis B infection, yearly, from 1994 to 1997. In the first area hepatitis B was found in 32.1% of children up to one year old and reached a peak of 68.7% in the age range of 15 to 19 years. In the control area the prevalence of hepatitis B was under 5% up to 19 years of age and the highest prevalence was observed in adults over 45. HBsAg was detected in 9.4% of the individuals living in the endemic area for schistosomiasis and in 1.4% of the controls (OR=4.98; 95%CI=3.7-6.7). The index of chronicity of HBsAg was not statistically different in the studied areas (8.1% x 7.3%; OR = 1.09; 95%CI= 0.42-3.03), nor was it different for people with and without schistosomiasis in Queixadinha (8.7% x 7.0%). We conclude that the Schistosoma mansoni infection has not altered the course of hepatitis B in the studied area.

The Epidemiological Impact of Antimeningococcal B Vaccination in Cuba

The incidence of invasive meningococcal disease (IMD) before (1984-1988) and after (1989-1994), a nationwide intervention with VA-MENGOC-BC vaccination started in 1989, was compared. The prevaccination period incidence density (ID> 8.8/ 105 year-person) was higher than the postvaccination ID (ID< 6.5/ 105 year-person). The percentage proportional differences from the start to the end of each period of ID in the vaccinal period was higher (87%) than the prevaccinal (37%) with significant differences among vaccinated groups (< 25 years old). A break-point (Chow test) was confirmed by the decrease in the ID between 1989 and 1990 in children under 1 year old, 5-9, 10-14, 15-19 and 50-54 years. Comparison of ID using maps showed a decrease in IMD in all municipalities during the postvaccination period. These findings support the epidemiological impact of VA-MENGOC-BC vaccination in the reduction of IMD morbidity.

Detection of Hepatitis B Virus Antigens in Paraffin-embedded Liver Specimens from the Amazon Region, Brazil

Hepatic viscerotomy of paraffin-preserved old specimens, collected in the period from 1934 to 1967, were analyzed by immunohistochemical assays to detect hepatitis B, hepatitis D, dengue and yellow fever virus antigens. The material belongs to the Yellow Fever Collection, Department of Pathology, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil and the cases were diagnosed at that time according to clinical aspects and histopathological findings reporting viral hepatitis, yellow fever, focal necrosis and hepatic atrophy. From the 79 specimens, 69 were collected at the Labrea Region and the other 10 in different other localities in the Amazon Region. The five micra thick histological slices were analyzed for the presence of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) by immunoperoxidase technique. An immunofluorescence assay was applied to the detection of hepatitis D, yellow fever and dengue virus antigens. Nine (11.4%) histological samples were HBsAg reactive and 5 (6.3%) were HBcAg reactive. The oldest reactive sample was from 1934. Viral antigens related to the other pathologies were not detected in this study. Our results confirm that the methodology described may be used to elucidate the aetiology of hepatitis diseases even after a long time of conservation of the specimens.

Seroprevalence of Hepatitis B virus infection among an afro-descendant community in Brazil

Furnas dos Dionísios is an Afro-Brazilian black community whose descendants were mainly fugitive slaves that established themselves in the State of Mato Grosso do Sul (MS), Brazil. The population is comprised mainly of low socioeconomic individuals who are engaged in agricultural activities. The objective of this study was to investigate the prevalence of hepatitis B (HB) and its correlation with epidemiological data obtained from the community. The studied population totaled 260 individuals with ages varying from 1 to 79 years (median 20). One hundred thirty-three (51.2%) were females and 127 (48.8%) were males. A high prevalence for anti-HBc was observed (42.7%), with present infection detected in 9.2% of the subjects who were also HB surface antigens (HBs Ag) positive; 27.3% were anti-HBc and anti-HBs reactive, and 6.2% had anti-HBc as only marker. The prevalence for anti-HBc was proportional to age, reaching its highest peak in age categories greater than 50. No serological marker was detected in children under the age of 2 years, however anti-HBc was present in 12 subjects with ages between 2 and 14 years, of these 8 (7.4%) were HBsAg positive. Among individuals over the age of 15 years, 99 were anti-HBc reactive, of these 16 (10.5%) were also HBsAg positive, thus suggesting an increased prevalence of HBV carriers among children and adolescents. The risk factors observed in this community that were significantly associated with anti-HBc positivity were age (over 20 years) and having an anti-HBc positive mother. Both HBeAg and anti-HBe were detected in 44.4% of the samples tested. HBsAg subtypes found in the studied population were adw2 (77.7%) and ayw2 (23.3%). While intrafamilial transmission was most likely responsible for HBV infection among children, other routes such as sexual contact might be considered for individuals with ages over 15 years.

Prevalence of hepatitis-B surface antigen among blood donors and human immunodeficiency virus-infected patients in Jos, Nigeria

Information is very scarce on the prevalence of hepatitis-B virus (HBV) infection among blood donors and patients with human immunodeficiency virus (HIV) infection in Nigeria. Hepatitis-B surface antigen (HBsAg) ELISA was used to determined the prevalence of HBsAg among 175 blood donors (aged 20-40 years) and 490 HIV-infected patients (aged 17-60 years) in Jos, Nigeria. Twenty-five (14.3%) of the blood donors and 127 (25.9%) of the HIV-infected individuals were HBsAg seropositive, indicating a higher HBV infection among HIV-infected persons than among healthy blood donors. A slightly higher HBsAg seroprevalence was recorded in the males (14.6%) than females (12.9%) of the blood donors. Among the HIV-infected patients, the males had considerably higher HBsAg seroprevalence than the females (31.8 vs 22.1%) with the highest prevalence of HBsAg occurring in the 51-60 years age group (44%), followed by those of 31-40 years (28.2%). Results confirmed the high endemicity of HBV infection in Jos, Nigeria and the significantly greater prevalence of HBV infection among HIV -infected patients than among blood donors.

Seroepidemiology of hepatitis B virus infection and high rate of response to hepatitis B virus Butang®vaccine in adolescents from low income families in Central Brazil

In order to evaluate the seroepidemiology and response to Butang® vaccine in adolescents from low income families in Central Brazil, blood samples of 664 adolescents were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs) markers, and multiple logistical regression analysis was carried out to determine variables associated with hepatitis B virus (HBV) infection markers. further, three 20 µg butang® vaccine doses were offered to all susceptible individuals (n = 304). Among those who accepted them (n = 182), the seroresponse was evaluated in 170 individuals by quantitative anti-HBs. an overall hbv prevalence of 5.9% was found: four adolescents were HBsAg positive, 24 were anti-HBc, anti-HBs-reactive, and 11 were anti-HBc only. The analyse of risk factors showed that age 16-19 years, place of birth outside Goiás, school B and body piercing were statistically associated with HBV infection markers (p < 0.05). All 170 adolescents responded to butang®, and a geometric mean titer (gmt) of 4344 mui/ml was obtained. these results reinforce the importance of hepatitis b vaccine in adolescents despite of the hbv regional endemicity, and suggest that three doses of 20 µg of the butang® should guarantee protective anti-hbs levels to individuals at a critical time for hepatitis b acquiring such as latter adolescence and adulthood.

Patterns of hepatitis B virus infection in Brazilian human immunodeficiency virus infected patients: high prevalence of occult infection and low frequency of lamivudine resistant mutations

Hepatitis B virus (HBV) molecular profiles were determined for 44 patients who were infected with human immunodeficiency virus (HIV) type 1 and had antibodies to the hepatitis B core antigen (anti-HBc), with and without other HBV serological markers. In this population, 70% of the patients were under lamivudine treatment as a component of antiretroviral therapy. HBV DNA was detected in 14 (32%) patients. Eight out of 12 (67%) HBsAg positive samples, 3/10 (30%) anti-HBc only samples, and 3/22 (14%) anti-HBs positive samples were HBV DNA positive. HBV DNA loads, measured by real time polymerase chain reaction, were much higher in the HBsAg positive patients (mean, 2.5 × 10(9) copies/ml) than in the negative ones (HBV occult infection; mean, 2.7 × 10(5) copies/ml). Nine out of the 14 HBV DNA positive patients were under lamivudine treatment. Lamivudine resistant mutations in the polymerase gene were detected in only three patients, all of them belonging to the subgroup of five HBsAg positive, HBV DNA positive patients. A low mean HBV load (2.7 × 10(5) copies/ml) and an absence of lamivudine resistant mutations were observed among the cases of HBV occult infection.

Seroprevalence of hepatitis B and C virus markers among blood donors in Rio de Janeiro, Brazil, 1998-2005

The prevalence of infection by hepatitis B (HBV) and C (HCV) viruses varies among geographical regions. In order to determine the prevalence of HBV and HCV infection in voluntary blood donors we evaluated the prevalence of HBsAg, anti-HBc, and anti-HCV markers of 128,497 blood donor samples collected from 1998 to 2005 in the state of Rio de Janeiro. These markers were analyzed by immunoenzymatic tests, as determined by the Ministry of Health. Data were obtained from the Sorology Laboratory of the Hemoterapy Service of the Instituto Nacional de Câncer, Rio de Janeiro. Overall prevalence estimates were: 0.27% for HBsAg, 3.68% for anti-HBc, and 0.90% for anti-HCV. There was a significant decrease in the overall prevalence of HBsAg (from 0.36 to 0.14%) and anti-HBc (from 6.12 to 2.05%) in the period encompassed between 1998-2005. Similarly, there was a decline in anti-HCV prevalence rates in Brazilian blood donors, from 1.04% in 1998 to 0.79% in 2004, with an increase of HCV prevalence to 1.09% in 2005. These prevalence estimates were higher than those found in other countries, indicating high rates of infection by HBV and HCV and a persistent risk of HBV and HCV transmission by transfusion.

Heterogeneous secretion of individual B cells in response to D-glucose and to nonglucidic nutrient secretagogues.

We used a hemolytic plaque assay for insulin to determine whether the same pancreatic B cells respond to D-glucose, 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (BCH) and the association of this nonmetabolized analogue of L-leucine with either the monomethyl ester of succinic acid (SME) or the dimethyl ester of L-glutamic acid (GME). During a 30-min incubation in the absence of D-glucose, BCH alone (5 mM) had no effect on insulin release. In contrast, the combination of BCH with either SME (10 mM) or GME (3 mM) stimulated insulin release to the same extent observed in the sole presence of 16.7 mM D-glucose. The effects of BCH plus SME and BCH plus GME on both percentage of secreting B cells and total insulin output were little affected in the presence of D-glucose concentrations ranging from 0 to 16.7 mM. Varying the concentration of SME from 2 to 10 mM also did not influence these effects. In other experiments, the very same B cells were first exposed 45 min to 16.7 mM D-glucose, then incubated 45 min in the presence of only BCH and SME. Under these conditions, most (80.3 +/- 2.5%) of the cells contributing to insulin release did so during both incubation periods. Furthermore, virtually all cells responding to BCH and SME during the second incubation corresponded to cells also responsive to D-glucose during the first incubation. Similar observations were made when the sequence of the two incubations was reversed.(ABSTRACT TRUNCATED AT 250 WORDS)