BKV-infection in kidney graft dysfunction.

INTRODUCTION: BKV nephropathy (BKN) causes kidney graft loss, whose specific diagnosis is invasive and might be predicted by the early detection of active viral infection. OBJECTIVE: Determine the BKV-infection prevalence in late kidney graft dysfunction by urinary decoy cell (DC) and viral DNA detection in urine (viruria) and blood (viremia; active infection). METHODS: Kidney recipients with >1 month follow-up and creatinine >1.5 mg/dL and/or recent increasing >20% (n = 120) had their urine and blood tested for BKV by semi-nested PCR, DC searching, and graft biopsy. PCR-positive patients were classified as 1+, 2+, 3+. DC, viruria and viremia prevalence, sensitivity, specificity, and likelihood ratio (LR) were determined (Table 2x2). Diagnosis efficacy of DC and viruria were compared to viremia. RESULTS: DC prevalence was 25%, viruria 61.7%, and viremia 42.5%. Positive and negative patients in each test had similar clinical, immunosuppressive, and histopathological characteristics. There was no case of viremia with chronic allograft nephropathy and, under treatment with sirolimus, patients had a lower viruria prevalence (p = 0.043). Intense viruria was the single predictive test for active infection (3+; LR = 2.8).1,6-4,9 CONCLUSION: DC, BKV-viruria and -viremia are commun findings under late kidney graft dysfunction. Viremia could only be predicted by intense viruria. These results should be considered under the context of BKN confirmation.

Polymorphism (ALA16VAL) correlates with regional lymph node status in breast cancer.

We studied the possible association between Ala16Val manganese-dependent superoxide dismutase (MnSOD) gene genotypes and breast cancer lymph node status because previous investigations suggested an association between the AA genotype and breast cancer. We included 281 women (188 controls and 93 cases of invasive breast cancer with axillary lymph node metastasis (LN+) and without lymph node metastasis (LN-). DNA was extracted from paraffin-embedded tumor tissue or peripheral blood leukocytes, and MnSOD polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism techniques. In addition, the immunohistochemical profile (p53, Ki-67 and estrogen/progesterone receptors) was also compared between invasive breast cancer groups and different MnSOD genotypes. The frequency of the VV genotype was higher in the LN+ group than in the control and LN- groups (chi(2)=5.081, P=0.02). Subjects with LN+ breast cancer (LN+ group) showed a higher incidence of VV genotype carriers associated with positive Ki-67 marker. Subjects with LN+ breast cancer (LN+ group) showed a higher incidence of VV genotype carriers associated with negative p53 marker. Despite the fact that the AA genotype is well established as being associated with an increased risk of breast cancer, the VV genotype may be associated with a higher metastatic potential, suggesting that MnSOD imbalance is the condition associated with carcinogenesis.

Prevalence of the hemochromatosis gene mutation in patients with nonalcoholic steatohepatitis and correlation with degree of liver fibrosis.

BACKGROUND: Nonalcoholic steatohepatitis is a chronic liver disease with a high prevalence in the general population and a potential to evolve into cirrhosis. It is speculated that iron overload could be associated with liver injury and unfavorable progress in affected patients. AIMS: To evaluate the prevalence of mutation of the hemochromatosis gene (HFE) in patients with nonalcoholic steatohepatitis and to correlate it with histological findings in liver specimens. PATIENTS AND METHODS: Twenty-nine patients with nonalcoholic steatohepatitis were evaluated. The presence of mutation in the hemochromatosis gene (C282Y and H63D) was tested in all patients and its result was evaluated in relation to hepatic inflammatory activity, presence of fibrosis, and iron overload in the liver. The control group was composed of 20 patients with normal liver function tests and 20 patients infected with the hepatitis C virus, with elevated serum levels of aminotransferases and with chronic hepatitis as shown by biopsy. RESULTS: Mutation of the hemochromatosis gene (C282Y and/or H63D) was diagnosed in 16 (55.2%) patients with nonalcoholic steatohepatitis, in 12 (60%) patients with hepatitis C and in 8 (40%) patients with no liver disease. No association was found between the presence of mutation and inflammatory activity, nor with the presence of fibrosis in patients with nonalcoholic steatohepatitis. An association was found between the presence of mutation and the occurrence of iron overload in liver, but there was no association between liver iron and the occurrence of fibrosis. CONCLUSIONS: The findings suggest that iron does not play a major role in the pathogenesis and progression of nonalcoholic steatohepatitis, and routine tests of the hemochromatosis gene mutation in these patients should not be recommended.

Prevalence of the hemochromatosis gene mutation in patients with nonalcoholic steatohepatitis and correlation with degree of liver fibrosis / Prevalência de mutação para o gene da hemocromatose em pacientes com esteatohepatite não-alcoólica e correlação com o grau de fibrose hepática

BACKGROUND: Nonalcoholic steatohepatitis is a chronic liver disease with a high prevalence in the general population and a potential to evolve into cirrhosis. It is speculated that iron overload could be associated with liver injury and unfavorable progress in affected patients. AIMS: To evaluate the prevalence of mutation of the hemochromatosis gene (HFE) in patients with nonalcoholic steatohepatitis and to correlate it with histological findings in liver specimens. PATIENTS AND METHODS: Twenty-nine patients with nonalcoholic steatohepatitis were evaluated. The presence of mutation in the hemochromatosis gene (C282Y and H63D) was tested in all patients and its result was evaluated in relation to hepatic inflammatory activity, presence of fibrosis, and iron overload in the liver. The control group was composed of 20 patients with normal liver function tests and 20 patients infected with the hepatitis C virus, with elevated serum levels of aminotransferases and with chronic hepatitis as shown by biopsy. RESULTS: Mutation of the hemochromatosis gene (C282Y and/or H63D) was diagnosed in 16 (55.2 percent) patients with nonalcoholic steatohepatitis, in 12 (60 percent) patients with hepatitis C and in 8 (40 percent) patients with no liver disease. No association was found between the presence of mutation and inflammatory activity, nor with the presence of fibrosis in patients with nonalcoholic steatohepatitis. An association was found between the presence of mutation and the occurrence of iron overload in liver, but there was no association between liver iron and the occurrence of fibrosis. CONCLUSIONS: The findings suggest that iron does not play a major role in the pathogenesis and progression of nonalcoholic steatohepatitis, and routine tests of the hemochromatosis gene mutation in these patients should not be recommended.

RACIONAL: A esteatohepatite não-alcoólica é uma doença crônica, com elevada prevalência na população e com potencial evolutivo. Especula-se que a sobrecarga de ferro possa estar associada com a injúria hepática e com uma evolução desfavorável destes pacientes. OBJETIVOS: Avaliar a prevalência da mutação do gene da hemocromatose (HFE) em pacientes com esteatohepatite não-alcoólica e correlacioná-la com os achados histológicos hepáticos. PACIENTES E MÉTODOS: Foram avaliados 29 pacientes com esteatohepatite não-alcoólica. A presença da mutação do HFE (C282Y e H63D) foi testada em todos os pacientes e seu resultado foi avaliado em relação a atividade inflamatória hepática, presença de fibrose e depósitos hepático de ferro. Como grupo controle estudou-se 20 pacientes com provas de função hepática normal e 20 pacientes portadores do vírus da hepatite C, com elevação dos níveis de aminotransferases e biópsia revelando hepatite crônica. RESULTADOS: A mutação do HFE (C282Y e/ou H63D) foi diagnosticada em 16 (55,2 por cento) pacientes com esteatohepatite não-alcoólica, em 12 (60 por cento) pacientes com hepatite C e em 8 (40 por cento) pacientes sem doença hepática. Não se observou associação entre a presença da mutação e a atividade inflamatória e a presença de fibrose nos pacientes com esteatohepatite não-alcoólica. Foi observada associação entre a presença de mutação e a ocorrência de depósitos de ferro hepático, porém, não ocorreu associação entre o ferro hepático e a ocorrência de fibrose. CONCLUSÕES: Os achados sugerem que o ferro não exerce papel importante na patogenia e na evolução da esteatohepatite não-alcoólica e a pesquisa rotineira da mutação do HFE nestes pacientes não deve ser recomendada.

Expression of Ki-67 and squamous intraepithelial lesions are related with HPV in endocervical adenocarcinoma.

To estimate the association between human papillomavirus (HPV) status and the expression of p53, Ki-67 and bcl-2 in cases of endocervical adenocarcinoma, and the relation with squamous intraepithelial lesions (SIL) and age, 229 cases were selected, treated between 1995 and 2003 in the Hospital Nossa Senhora da Conceiçao. All samples were evaluated by polymerase chain reaction to determine HPV status. Immunohistochemical technique was used to investigate the expression of p53, Ki-67 and bcl-2. The joint occurrence of endocervical adenocarcinoma and SIL were estimated too. In the 229 evaluated cases, 182 cases (79.48%) were associated with the presence of the HPV. The most common types were HPV18 (93 cases - 51.09%) and HPV16 (62 cases - 34.06%). Expression of Ki-67 (p=0.009) and the presence of SIL (p=0.018) were associated to HPV infection. Expression of p53 (p=0.647) and bcl-2 (p=0.671) were not related to HPV status. The mean age of the patients was 53.2 years, without clear correlation between age group and HPV (p=0.095). The presence of HPV, especially type 18 in endocervical adenocarcinoma suggests that this agent can be an important cofactor in the development and progression of glandular neoplasms of the uterine cervix. The joint occurrence of endocervical adenocarcinoma and SIL may support this hypothesis. HPV may promote an increased proliferation index in endocervical adenocarcinoma, shown by the expression of Ki-67.

Vertical transmission of hepatitis C virus in a hospital in southern Brazil.

BACKGROUND: There still are controversies concerning the vertical transmission of hepatitis C virus. AIM: To evaluate the prevalence of antibodies against hepatitis C virus in pregnant women, as well as the rate of vertical transmission of this virus. PATIENTS AND METHODS: Between August 1998 and November 1999, 1,090 consecutive pregnant women were screened for anti-hepatitis C virus; positive results were confirmed by the polymerase chain reaction assay. Patient's viral load was evaluated by the branched deoxyribonucleic acid assay. Hepatitis C virus genotype was identified by direct sequencing of the polymerase chain reaction amplification products. The same tests were performed in the children born from infected mothers at the 1st and 6th month of life. RESULTS: Of the 1,090 mothers surveyed, 29 were positive for anti-hepatitis C virus (prevalence of 2.66%). Twenty-five patients presented with hepatitis C virus RNA, with a median hepatitis C virus viral load of 3.132 +/- 5.891 MEq/mL. Twenty-two patients (six human immunodeficiency virus-coinfected) were followed and gave birth to 23 children; 18 of them had blood samples tested at the 1st month of life, and 22, at the 6th month. Vertical transmission rate was 5.56%; it affected a girl who had hepatitis C virus RNA detectable only in the 1st month sample (41.570 MEq/mL). The mother who transmitted hepatitis C virus was coinfected with human immunodeficiency virus and presented with an hepatitis C virus viral load of 3.765 MEq/mL, with 100% homology with her daughter's hepatitis C virus genotype. CONCLUSION: These results suggest that the prevalence of hepatitis C virus infection in pregnant women should not be neglected, and early diagnosis of vertical transmission and the follow up of infected children should be emphasized.

Hepatitis B vaccine efficacy in patients with chronic liver disease by hepatitis C virus

RACIONAL: Considerando a imunossupressão dos pacientes com doença hepática crônica, sua resposta à vacinação é discutida na literatura. OBJETIVOS: Avaliar a resposta à vacina anti-hepatite B em pacientes com hepatite crônica pelo vírus C. MÉTODOS: Estudo prospectivo avaliando 85 pacientes com infecção pelo vírus C (46,8 ± 9,4 anos, 44,7% homens) e 46 adultos saudáveis (36,7 ± 11,1 anos, 39,1% homens). Carga viral foi determinada através do b-DNA em 74 pacientes e o genótipo foi determinado por seqüenciamento em 73 pacientes. Todos os pacientes e os adultos saudáveis receberam três doses da vacina Engerix B® IM (aos 0, 30 e 180 dias). Resposta sorológica à vacina foi dividida em três categorias: soroproteção, quando anti-HBs era >"100 mUI/mL; soroconversão, quando anti-HBs era 10-99 mUI/mL e não-reagente, quando anti-HBs era <10 mUI/mL. RESULTADOS: A resposta da vacina anti-hepatite B em 1 mês após a dose 3 foi soroproteção em 37,7%, soroconversão em 17,6% e não-reagente em 44,7% entre os pacientes, e 84,8%, 13,0% e 2,2%, respectivamente em adultos saudáveis. O número de respostas não-reagentes foi significativamente maior em pacientes com doença hepática crônica. Sessenta e cinco pacientes com hepatite crônica foram comparados a 20 cirróticos compensados em relação à resposta à vacina, mas nenhuma diferença foi observada. A resposta à vacina nos pacientes com genótipos 2 ou 3 (n = 40) foi melhor do que naqueles com genótipo 1 (n = 33). A resposta não foi relacionada com a concentração de VHC-RNA. CONCLUSÃO: O número de não-respondedores foi maior em pacientes com infecção crônica pelo vírus C, independentemente do "status" histológico e da carga viral. É sugerido que tais pacientes deveriam receber uma dose dupla de vacina, particularmente aqueles com genótipo 1.

Vertical transmission of hepatitis C virus in a hospital in southern Brazil

RACIONAL: Ainda existem controvérsias em relação à transmissão vertical do vírus da hepatite C (VHC). OBJETIVO: Avaliar a prevalência dos anticorpos contra o VHC (anti-VHC) em mulheres grávidas, bem como a percentagem de transmissão vertical observada. PACIENTES E MÉTODOS: Entre agosto de 1998 e novembro de 1999, 1.090 mulheres grávidas consecutivas realizaram a determinação do anti-VHC. A confirmação do teste foi feita pela reação em cadeia da polimerase. A carga viral foi determinada pelo b-DNA e o genótipo por seqüenciamento. Os mesmos testes foram realizados no 1º e 6º mês de vida, nas crianças nascidas de mães infectadas. RESULTADOS: Das 1.090 mães estudadas, 29 apresentaram positividade para o anti-VHC (prevalência de 2,66%). Em 25 pacientes foi demonstrado o RNA do VHC, sendo que a carga viral média foi de 3,132 ± 5,891 MEq/mL. Vinte e duas pacientes (6 co-infectadas com o vírus da imunodeficiência humana) foram seguidas e deram à luz a 23 crianças, das quais 18 tiveram seu sangue testado no 1º mês e 22 no 6º mês. Foi observada transmissão vertical em 5,56% dos casos. Assim, em uma criança do sexo feminino foi detectado o RNA do VHC (41,570 MEq/mL). A mãe desta criança estava co-infectada pelo vírus da imunodeficiência humana e apresentava carga viral de 3,765 MEq/mL, com 100% de homologia no genótipo viral. CONCLUSAO: Estes resultados sugerem que a prevalência da infecção pelo VHC em gestantes não deve ser negligenciada e que um diagnóstico precoce e o seguimento das crianças infectadas deve ser preconizado.

Hepatitis B vaccine efficacy in patients with chronic liver disease by hepatitis C virus.

BACKGROUND: Considering the immunosuppression of patients with chronic liver disease, their response to vaccination is discussed in literature. AIMS: To evaluate the response of hepatitis B vaccine in patients with chronic hepatitis C virus infection. METHODS: This is a prospective study in which 85 patients with chronic hepatitis C virus infection (46.8 +/- 9.4 years, 44.7% males) and 46 healthy adults (36.7 +/- 11.1 years; 39.1% males) were evaluated. Confirmation of hepatitis C virus was obtained by the technique of polymerase chain reaction. Viral load was determined by the branched DNA method in 74 patients, and genotype was determined by sequencing in 73 patients. All patients and healthy adults received three doses of Engerix B vaccine IM (at 0, 30 and 180 days). Serological responses to the vaccine were divided into three categories: seroprotection, when anti-HBs was > or =100 mUI/mL; seroconversion, when anti-HBs was 10-99 mUI/mL, and non-reagent, when anti-HBs was <10 mUI/mL. RESULTS: The response of hepatitis B vaccine as determined 1 month following dose 3 was seroprotection in 37.7%, seroconversion in 17.6% and non-reagent in 44.7% among patients and 84.8%, 13.0%, 2.2%, respectively in healthy adults. The number of non-reagent responses was significantly higher among those patients with chronic liver disease. Sixty-five patients with chronic hepatitis were compared to 20 compensated cirrhotic patients in concern to the response to vaccine, but no difference was found. The response to vaccine in patients with genotypes 2 or 3 (n = 40) was better than in those with genotype 1 (n = 33). Response was not related to serum HCV-RNA concentration. CONCLUSION: The number of non-responders was higher in patients with chronic hepatitis C virus infection, irrespective of histological status and viral load. It is suggested that such patients should receive a double dose of vaccine, particularly the ones with genotype 1.

Vírus da hepatite C em gestantes: prevalência e avaliação do risco do aleitamento materno / Hepatites C virus in pregnant women: prevalence and evaluation of breast - feeding risk

Este estudo avaliou a prevalência do anti-HCV em gestantes de um hospital geral, bem como a presença do vírus da hepatite C (VHC) no leite materno. Para tanto, foram avaliadas prospectivamente 1.090 gestantes, nas quais foi realizada a pesquisa do anti-HCV. Nas pacientes reagentes foi feita a pesquisa do RNA viral pela reação em cadeia da polimerase (PCR), sendo que nas que amamentavam foram colhidas amostras de leite para pesquisa do HCV RNA. Observou-se uma prevalência do anti-HCV em 2,66 por cento das gestantes, sendo que o HCV RNA foi positivo em 82,61 por cento das analisadas. Seis gestantes apresentavam coinfecção pelo vírus da imunodeficiência humana. Quando se avaliaram 12 amostras de leite materno, o HCV RNA foi negativo. Os autores concluem que a prevalência do VHC em gestantes não deve ser desconsiderada e que o aleitamento materno não é um fator relevante na transmissão do VHC.