Hepatitis: Vitvitski L

Paraná R, Vitvitski L, Pereira JE. · Gastro-Hepatology Unit, University Hospital, Federal University of Bahia, Salvador, BA, Brazil. · Braz J Infect Dis. · Pubmed #18833412 links to  free full text

Abstract: 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. Initial epidemiological studies have further demonstrated a high prevalence of Hepatitis C in the western Brazilian Amazon. The geographic, cultural, ethnic and environmental aspects of this region may favor hepatotropic virus dissemination, as well as rendering difficult the implementation of governmental programs in the treatment of patients and prevention of disease dissemination.

Merle P, Zoulim F, Vitvitski L, Trépo C. · Laboratoire de Recherche sur les Hépatites et Pathologies Associées, INSERM U 271, cours Albert-Thomas, 69424 Lyon Cedex 03, France. · Gastroenterol Clin Biol. · Pubmed #11173729 No free full text.

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Bengochea A, de Souza MM, Lefrançois L, Le Roux E, Galy O, Chemin I, Kim M, Wands JR, Trepo C, Hainaut P, Scoazec JY, Vitvitski L, Merle P. · INSERM, U871, Molecular Physiopathology and New Therapies in Viral Hepatitis, 151 cours Albert Thomas, Lyon, F-69424, France. · Br J Cancer. · Pubmed #18577996 links to  free full text

Abstract: 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. Immunostaining was performed to localise Frizzled on cell types in liver tissues. Regulation of three known Frizzled-dependent pathways (beta-catenin, protein kinase C, and C-Jun NH(2)-terminal kinase) was measured in tissues by western blot. We found that eight Frizzled-potentially activating events were pleiotropically dysregulated in 95% HCC and 68% peritumours as compared to normal livers (upregulations of Frizzled-3/6/7 and Wnt3/4/5a, or downregulation of sFRP1/5), accumulating gradually with severity of fibrosis in peritumours and loss of differentiation status in tumours. The hepatocytes supported the Wnt/Frizzled signalling since specifically overexpressing Frizzled receptors in liver tissues. Dysregulation of the eight Frizzled-potentially activating events was associated with differential activation of the three known Frizzled-dependent pathways. This study provides an extensive analysis of the Wnt/Frizzled receptor elements and reveals that the dysregulation may be one of the most common and earliest events described thus far during hepatocarcinogenesis.

Almeida D, Tavares-Neto J, Vitvitski L, Almeida A, Mello C, Santana D, Tatsch F, Paraná R. · Faculty of Medicine of Bahia, Post-graduation Program in Health and Medicine, Salvador, Bahia, Brazil. · Braz J Infect Dis. · Pubmed #17293918 links to  free full text

Abstract: 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. Cross sectional study. Blood samples were tested for serological markers of hepatitis A (HAV), B (HBV) and C (HCV) through ELISA-III assay. In HBsAg and anti-HCV carriers, HCV-RNA and HBV-DNA were checked by PCR. The prevalence of anti-HAV IgG was 83.3% (1,210/1,452), being higher among residents from the village (87.4%) than in residents from the rural area (79.5%); it also higher among individuals older than 10 years of age. The prevalence of HBsAg was 2.6% (38/1,476), 9.3% anti-HBc (137/1,476) and 10.5% (155/1,476) anti-HBs of. In more than half (58.1%; 90/155) of anti-HBs carriers, this was the only serological marker found. In 3.7% of the population, (55/1,476), anti-HBc was the only serological marker found. All HBV carriers were infected by genotype A. Only 0.4% (6/1,536) presented anti-HCV antibodies and only one of them was viremic, being infected with genotype 1. The prevalence of patients with antibodies against hepatitis A virus in the village of Cavunge was high, but the prevalence of B virus was moderate, with only genotype A among HBV carriers. The prevalence of C virus was very low, contrasting with the situation in large Brazilian urban centers.

Lobato C, Tavares-Neto J, Rios-Leite M, Trepo C, Vitvitski L, Parvaz P, Zoulim F, D'Oliveira A, Paraná R. · CPgMS-State of Acre Cooperation Program with University of Bahia, Bahia, Brazil. · J Gastroenterol Hepatol. · Pubmed #16704537 No free full text.

Abstract: 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. RESULTS: The overall prevalence of HBV carriers (HBsAg) and exposed individuals (anti-HBc, IgG) was, respectively, 21.1% and 60.5% in G1 and 2.8% and 27.4% in G2 (P < 0.0000001). The frequency of HBsAg was higher among siblings from group G1 (75%) compared to the absence of any HBsAg-positive sibling in G2 (P < 0.00006). The HBV markers in other family members was as follows: G1 parents, 27.3% vs 4.5% (P < 0.03), sexual partners, 21.1% vs 2.5% (P < 0.04), and offspring, 10.4% vs 1.5% (P < 0.04). A low prevalence of HBsAg and anti-HBc (IgG) was observed for the last offspring of G2 mothers compared to the high prevalence among children of G1 mothers (0% vs 18.2%, P < 0.01 and 2.3% vs 59.1%, P < 0.0000005, respectively), with children younger than 1 year being the most affected. The frequency of the habit of sharing toothbrushes and the presence of at least one HBsAg carrier were higher in G1 than in G2 (P < 0.0001 and P < 0.000002), respectively. Genotypes A, D and G were found to be predominant by Innolipa test. There were cases that reacted to more than one genotype. CONCLUSION: Intrafamilial transmission of HBV is evident in the present study and is possibly associated with the presence of more than one HBV carrier in the family and the shared use of toothbrushes among household contacts. Genotype analysis confirms intrafamilial transmission.

Merle P, Kim M, Herrmann M, Gupte A, Lefrançois L, Califano S, Trépo C, Tanaka S, Vitvitski L, de la Monte S, Wands JR. · Department of Medicine and Pathology, Brown Medical School, The Liver Research Center, Providence, 55 Claverick St., 4th Floor, Providence, RI 02903, Rhode Island 02903, USA. · J Hepatol. · Pubmed #16098625 No free full text.

Abstract: 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. METHODS: We employed single (c-myc, SV40-Tag) and established double [insulin receptor substrate-1 (IRS-1/c-myc) and hepatitis Bx protein (X/c-myc)] transgenic lines and all developed HCC. Expression of 9 FZD was measured by real time RT-PCR and Western blot analysis. Phosphorylation and cellular accumulation of beta-catenin were assessed in both dysplastic tissue and tumors. We investigated the effect of a dominant negative (DN) FZD7 on TCF transcriptional activity in a SV40 derived HCC cell line. RESULTS: FZD7 was highly overexpressed at the mRNA and protein level(s) in HCC and occurred in dysplasia. Upregulation of FZD7 was associated with reduced phosphorylation of beta-catenin and led to nuclear accumulation in HCC tumors. Ectopic expression of a DN FZD7 construct decreased TCF transcriptional activity in tumor cells. CONCLUSIONS: These observations suggest that upregulation of FZD7 receptors in association with activation of the canonical Wnt/beta-catenin pathway is a common molecular event in HCC.

Tavares-Neto J, Prata A, Paraná R, Valente VB, Vitvitski L, Figueiredo JF. · Faculty of Medicine of Bahia, Federal University of Bahia, R. Marquês de Caravelas 262/101, 40140-210 Salvador, Bahia, Brazil. · Rev Soc Bras Med Trop. · Pubmed #16082473 links to  free full text

Abstract: 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. Anti-HCV markers were assayed by ELISA-II and RIBA-II in serum samples obtained from 1,228 residents (85.8%). The anti-HCV antibody (ELISA-II) was positive in six (0.5%) individuals, eight (0.6%) cases were inconclusive and 1,214 (98.9%) were negative. However, only in one ELISA-positive serum sample (0.08%) were antibodies confirmed by RIBA-II, while two other samples assayed by RIBA-II were indeterminate. These three patients presented the hepatointestinal form of SM during the follow-up period (1976 to 1996). In conclusion, no association was observed between HCV and SM in the endemic area studied, especially among patients with the hepatosplenic form of the disease.

Tavares-Neto J, Almeida D, Soares MC, Uchoa R, Viana S, Darub R, Farias E, Rocha G, Vitvitski L, Paraná R. · Postgraduate Program, University of Bahia, Group for the Study of Viral Hepatitis, Salvador, BA, Brazil. · Braz J Infect Dis. · Pubmed #15361991 links to  free full text

Abstract: 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. The individuals with previous HBV contact were significantly older (p<0.001) than those without HBV markers. Of the 192 individuals who returned for reexamination, 30 days after the third dose, 158 (82.3%) had received three vaccine doses, and only 60 (31.2%) belonged to the group without HBV markers. In these individuals, the seroconversion rate after the third dose was 92% (55/60). In conclusion, we found considerable HBV in this population, indicating the need for pursuing the immunization programs. We also found high rates of vaccination coverage in the Western Brazilian Amazon region.

Paraná R, Vitvitski L, Berby F, Portugal M, Cotrim HP, Cavalcante A, Lyra L, Trepo C. · Gastro-Hepatology Unit, University Hospital of Bahia, Brazil. · Arq Gastroenterol. · Pubmed #11460601 links to  free full text

Abstract: 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 (57.9%) males and 99 (42.1%) females, followed in the liver disease referral unit in Salvador, BA, northeastern Brazil. All of them were anti-HCV positive by 3rd generation ELISA assay, and HCV-RNA positive by RT-PCR. Genotyping was performed by INNOLIPA. Assessment of risk factors for HCV infection showed that 93 (40%) had past blood transfusion, 14 (6%) intravenous drug use, 19 (8%) inhalation of cocaine, 28 (12%) tattooing, 15 (7%) were health care workers, 5 (2%) had reused disposable syringes, 5 (2%) had multiple risk factors and in 53 (23%) no risk factor was determined. Genotype 1a was observed in 75 (32%), 1b in 72 (31%), 3a in 61 (26%), 2ab in 14 (6%); 5 (2.5%) had mixed genotypes and 5 (2.5%) were undetermined. Patients with genotype 1 had a higher mean age (P < 0.05) and no particular risk factors were associated with a specific genotype. Genotype 1 largely predominates in northeast Brazil followed by genotype 3 which, in this population, does not seem to be related to intravenous drug abuse, in contrast to some European studies. Although 80% of the Salvador population comprises African-Brazilians, no African genotype was identified, which may mean that HCV was introduced into this region via European immigration. This study demonstrated some peculiarities of HCV epidemiology in Brazil and strongly suggests that HCV introduction to this region was probably related to European immigration.

Paraná R, Portugal M, Vitvitski L, Cotrim H, Lyra L, Trepo C. · Gastro-Hepatology Unit, University Hospital of Bahia, Brazil. · Eur J Gastroenterol Hepatol. · Pubmed #10741943 No free full text.

Abstract: 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. Here, we describe two cases of severe strongyloidiasis coincident with ribavirin plus interferon therapy for treating HCV infection. The review of our monotherapy protocol with interferon did not disclose any case of symptomatic strongyloidiasis pointing to a possible role of ribavirin in modifying immune response to S. stercoralis. We propose a careful screening for S. stercoralis before initiating ribavirin therapy or even empiric antihelmintic treatment.

Paraná R, Vitvitski L, Andrade Z, Trepo C, Cotrim H, Bertillon P, Silva F, Silva L, de Oliveira IR, Lyra L. · Hepatology Unit of Bahia, University Hospital of Bahía, Brazil. · Hepatology. · Pubmed #10385669 No free full text.

Abstract: 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. The initial clinical and biochemical presentation of the HCV and non-A-E cases was quite similar, although 2 of the non-A-E patients had severe disease. The 5 patients who were found to be anti-HEV IgG-reactive recovered within 6 months of follow-up. Of the 13 HCV cases, alanine transaminase (ALT) levels returned to normal in 7 (53. 8%), while 6 (46.2%) continued to show abnormal ALT after 6 months of follow-up. However, 9 (69.2%) of them remained HCV-RNA-positive, denoting virological/biochemical dissociation. Long-term follow-up showed a reappearance of HCV RNA in 2 of the 4 patients who were in virological remission performing 84% of chronicity rate. Acute non-A-E hepatitis patients were less likely to evolve toward chronicity, as compared with acute HCV cases (16% vs. 84%; P =.0001). Only 4 (16%) of the non-A-E patients were hepatitis G virus (HGV)-RNA-positive. Concerning risk factors for acquiring parenterally transmitted viruses, tattooing was the only one that could be associated with HCV transmission (P =.002). No risk factors could be identified for putative non-A-E virus transmission. Liver biopsies performed for chronic HCV patients showed a variable degree of inflammation, while the non-A-E patients presented less severe histological disease.

Paraná R, Trepo C, Vitvitski L, Lyra L. · No affiliation provided · Am J Gastroenterol. · Pubmed #10086693 No free full text.

This publication has no abstract.