Hepatotropic viruses in the Brazilian Amazon: a health threat.

Viral Hepatitis B, C and D are a serious public health problem in Brazil and other South American countries, mainly in the Amazonian region. Despite the paucity of clinical and epidemiological studies, a high prevalence of Hepatitis viruses has often been described in this area. Genotype F of Hepatitis B and Genotype III of Hepatitis D have been found to be quite prevalent in this area and preliminary studies have implicated both genotypes in carcinogenesis and peculiar pathogenic liver mechanisms.

Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma.

Dysregulation of growth factors and their receptors is central to human hepatocellular carcinoma (HCC). We previously demonstrated that the Frizzled-7 membrane receptor mediating the Wnt signalling can activate the beta-catenin pathway and promotes malignancy in human hepatitis B virus-related HCCs. Expression patterns of all the 10 Frizzled receptors, and their extracellular soluble autoparacrine regulators (19 Wnt activators and 4 sFRP inhibitors) were assessed by real-time RT-PCR in 62 human HCC of different etiologies and their matched peritumorous areas.

Serological markers of hepatitis A, B and C viruses in rural communities of the semiarid Brazilian northeast.

In the village of Cavunge, located in a dry tropical, semiarid rural region of the state of Bahia, Brazil, a sentinel study on viral hepatitis is underway. We report on the first part of the study. The objective of this study was to determine the prevalence of serological markers for hepatitis A, B and C in the village.

Intrafamilial prevalence of hepatitis B virus in Western Brazilian Amazon region: epidemiologic and biomolecular study.

Background: Hepatitis B is endemic in the Amazon region.

Methods: Serological markers for hepatitis B virus (HBV) were determined in 266 household members for hepatitis B surface antigen (HBsAg)-positive women (G1) and 395 household members for HBsAg-negative women (G2), randomly selected in Acre State Women's Medical Care Program, in order to evaluate the prevalence of HBV in this population. Before blood sample collection an epidemiological questionnaire was applied.

Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular carcinoma.

Background/aims: The molecular mechanisms of hepatocarcinogenesis remain largely unknown. Previous studies suggest that activation of the Wnt/beta-catenin pathway is important during hepatocyte transformation but the role of Frizzled receptor (FZD) in this process has not been defined. Here we investigate activation of this pathway by FZD using transgenic hepatocellular carcinoma (HCC) murine models.

Very low prevalence of hepatitis C virus infection in rural communities of northeastern Brazil with a high prevalence of schistosomiasis mansoni.

The association of hepatitis C virus infection and the hepatosplenic form of schistosomiasis mansoni has been claimed to result in the concomitant evolution of the two pathologies, with a poor prognosis due to aggravated liver disease. Recently, however, some authors have begun to reject the hypothesis of a higher susceptibility of hepatosplenic schistosomal patients to HCV. The aim of the present transverse study carried out between July and August 1990 was to determine the possible association between SM and HCV markers in residents of Catolândia, Bahia State.

Increase of doxorubicin sensitivity by doxorubicin-loading into nanoparticles for hepatocellular carcinoma cells in vitro and in vivo.

Background/aims: Hepatocellular carcinoma (HCC) is known to be chemoresistant to anticancer drugs due to the multidrug resistant (MDR) transporters expression. Here, we compared in vitro and in vivo the anti-tumor efficacy of doxorubicin-loaded polyisohexylcyanoacrylate nanoparticles (PIHCA-Dox) versus free doxorubicin (Dox). These nanoparticles are known to overcome the MDR phenotype.

Seroprevalence of hepatitis B and C in the Western Brazilian Amazon region (Rio Branco, Acre): a pilot study carried out during a hepatitis B vaccination program.

In 1999, on the occasion of the application of the first vaccine dose during the state vaccination campaign against hepatitis B virus (HBV), 390 individuals from the town of Rio Branco, Acre, aged two or more years were selected for the determination of the seroprevalence of HBV and HCV. HBV markers (HBsAg, anti-HBs, and anti-HBc IgG) were determined on this occasion and anti-HBs antibodies were also assessed 30 days after the third vaccine dose. At the time of vaccination, 39% of the individuals were still susceptible to HBV, while 61% presented serologic evidence of previous HBV contact or previous vaccination.

HCV infection in northeastern Brazil: unexpected high prevalence of genotype 3a and absence of African genotypes.

The genomic diversity of HCV embraces 6 genotypes and at least 52 subtypes with clinical and epidemiological correlations. There is a paucity of studies assessing HCV genotypes and biomolecular epidemiology in Brazil. We studied genotype distribution and epidemiological aspects in 232 HCV carriers, 133 (57.

Severe strongyloidiasis during interferon plus ribavirin therapy for chronic HCV infection.

Ribavirin is a nucleoside analogue, recently introduced in hepatitis C virus (HCV) therapy, that has postulated immunomodulatory and immunosuppressive action. Strongyloidiasis is an helmintic infection caused by Strongyloides stercoralis, endemic in tropical countries. Severe strongyloidiasis has been demonstrated after immunosuppression by corticosteroids evolving some fatal cases.

Acute sporadic non-A, non-B hepatitis in Northeastern Brazil: etiology and natural history.

In a 4-year follow-up study, patients with acute sporadic non-A, non-B (NANB) hepatitis were evaluated to determine the etiology and natural history of the disease. Acute hepatitis C virus (HCV) was detected in 13 of 43 (30%) of patients, anti-hepatitis E virus (HEV) IgG in 5 (12%), and 25 (58%) were considered non-A-E. The HCV RNA was detected in all HCV patients but none of the non-A-E cases.

Modulation of immune responses to hepatitis C virus envelope E2 protein following injection of plasmid DNA using single or combined delivery routes.

Different delivery routes of plasmid DNA may result in the induction of differential humoral and cellular immunity. We have studied the influence of two main routes of plasmid injection, performed intramuscularly and intraepidermally using a gene gun, for the induction of immune responses specific to hepatitis C virus (HCV) envelope protein E2. Three plasmids expressing different immunogenic domains of E2 (amino acids [aa] 384443, aa 504-555, and aa 384-746) were injected into BALB/c mice according to five different protocols using various combinations of intramuscular (i.

Immunization with plasmid DNA encoding hepatitis C virus envelope E2 antigenic domains induces antibodies whose immune reactivity is linked to the injection mode.

Plasmids expressing different domains of the hepatis C virus (HCV) envelope E2 glycoprotein from a genotype 1a isolate were constructed to compare the immunogenic potential of E2 in nucleic acid-based immunizations. One plasmid, pCIE2t, expressed a C-terminally truncated form of E2, while others, pS2.SE2A to pS2.

DNA vaccination for the induction of immune responses against hepatitis C virus proteins.

Recent analysis of clinical and experimental cases of hepatitis C virus (HCV) infection suggest the possible role of the viral nucléocapsid (C), the nonstructural protein 3 (NS3) and the envelope glycoproteins E1 and/or E2 in the mounting of immune responses capable to control infection (Botarelli et al., Gastroenterology, 1993, 104, 580-587; Choo et al., Proc.

Plasmid DNA expressing a secreted or a nonsecreted form of hepatitis C virus nucleocapsid: comparative studies of antibody and T-helper responses following genetic immunization.

In a murine model, we have compared humoral and T-helper (Th) responses induced following genetic immunization with two hepatitis C virus (HCV) plasmid-derived immunogens: a plasmid expressing the full-length nucleocapsid (CAP) as a nonsecreted antigen (pCMVC2) and a plasmid expressing the amino-terminal part of CAP as a secreted antigen (pS2S.C2N). In BALB/c mice, intramuscular injection of either plasmid induced IgG2a antibodies associated with a Th1-like profile characterized by the in vitro splenic production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma).

[Efficacy of interferon alpha in primary prevention of preneoplastic lesions in a transgenic murine model of hepatocellular carcinoma related to the interaction between woodchuck hepatitis viruses and c-myc oncogene].

Objectives: C-myc oncogene overexpression by near insertion of hepatitis B virus is important in woodchuck hepatocarcinogenesis. This DNA fragment was transferred in mice who developed hepatocellular carcinoma via preneoplastic lesions. In the present study, we tested the preventive effect of alpha interferon on the incidence of hepatocyte dysplasia.

[Treatment of hepatitis C].

The treatment of hepatitis C virus (HCV) infections is essentially known for chronic hepatitis C and is mainly restricted to interferon alpha. Initial trials have indicated that around 50% of the patients with chronic hepatitis C respond to alpha interferon (administered at 3 MU, thrice weekly, during 6 months) by normalizing alanine aminotransferase at the end of therapy, although 25% were found to relapse after therapy. Normalization of biochemical tests is associated with an improvement in liver histological features and with decrease or loss of HCV from serum and liver.

DNA-based immunization with chimeric vectors for the induction of immune responses against the hepatitis C virus nucleocapsid.

Vectors expressing the first 58 amino acids of the hepatitis C virus (HCV) nucleocapsid alone or as a fusion protein with the middle (pre-S2 and S) or major (S) surface antigens of hepatitis B virus (HBV) were constructed. Intramuscular immunization of BALB/c mice with the chimeric constructs in the form of naked DNA elicited humoral responses to antigens from both viruses within 2 to 6 weeks postinjection. No anti-HCV responses were obtained in mice immunized with the vector expressing the HCV sequence in the nonfusion context.

Serial transmission of spongiocytic hepatitis to woodchucks (possible association with a specific delta strain).

Background/aims: Outbreaks of severe hepatitis have been reported from Africa and South America. Description of the cases has shown the histological hallmark to be the presence of ballooning hepatocytes with fat drops surrounding the nucleus (spongiocytes or morula cells).

Methods: Experimental reproduction of this syndrome for the verification of a possible role of a specific HDV strain was performed by the inoculation of serum and liver extracts from African patients (Bangui-Central African Republic), who died with this syndrome, into American woodchuck carriers of WHV (WC 231,144), the results of which were then compared with animals inoculated with a reference wild HDV strain (WC 300,173,154), and those which received material from a European fulminant HDV case (WC 88,93).

Single-step nested polymerase chain reaction for detection of different genotypes of hepatitis C virus.

Hepatitis C virus (HCV) exhibits considerable sequence variability and circulates in the blood at extremely low levels. Current methods for detecting HCV RNA are based mostly on nested polymerase chain reaction (PCR), in which part of the first amplification product is reamplified in the second tube by an internal primer pair. A novel nested PCR method was developed in which the two successive amplification processes are carried out in the same tube with a single step of physical manipulation.

Characterization of the third most common genotype of hepatitis C virus in France.

We have previously identified the two major hepatitis C virus (HCV) genotypes prevalent in France (type I and type II). We report here the identification and partial characterization of a new HCV genotype with a highly divergent 5' noncoding (NC) region and a structural protein region. This genotype showed only 93-94% sequence identity with either type I or type II HCV in the 5' NC region.

Clinical relevance of the detection of hepatitis delta virus RNA in serum by RNA hybridization and polymerase chain reaction.

Hepatitis delta virus nucleic acid was detected by dot-blot hybridization using RNA probe and reverse transcription/polymerase chain reaction amplification in 223 serum samples from 66 patients with hepatitis D virus infection. Seven cases with chronic hepatitis D virus infection were treated with interferon: six for 3 months and one for 7.5 years.