Tratamento por esplenectomia de um aneurisma de veia porta na esquistossomose hépato-esplênica

Aneurismas venosos portais são uma entidade médica rara, ao passo que as esquistossomoses ainda constituem uma pandemia. Descrevemos um paciente de 46 anos, com esquistossomose hépato-esplênica e um aneurisma intra-hepático confirmado por vários métodos de imagem. Após a esplenectomia, o diâmetro do aneurisma diminuiu significativamente.Portal vein aneurysm is a rare medical entity that can be caused by chronic hepatic diseases with portal hypertension. We describe a 45-year-old man with variceal bleeding from hepatosplenic schistosomiasis and an incidentally found intrahepatic aneurysm. Diagnosis was confirmed with non-invasive imaging exams, arteriography and liver biopsy. Following splenectomy, the aneurysm diameter decreased substantially

Fatores precipitantes na porfiria cutânea tardia no Brasil com ênfase\ud nas mutações do gene (HFE) da hemocromatose. Estudo de 60 casos

BACKGROUND:\ud Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil.\ud \ud OBJECTIVES:\ud Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations.\ud \ud METHODS:\ud An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR.\ud \ud RESULTS:\ud Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors.\ud \ud CONCLUSIONS:\ud Alcohol abuse, hepatitis C and estrogen intake are prevalent precipitating factors in our porphyria cutanea tarda population; however, hemochromatosis in itself can also contribute to the outbreak of porphyria cutanea tarda, which makes the research for HFE mutations necessary in these patientsFUNDAMENTOS:\ud A porfiria cutânea tardia é a forma mais comum das porfirias e caracteriza-se pela diminuição da atividade da enzima uroporfirinogênio descarboxilase. Há vários relatos da associação das mutações do gene HFE da hemocromatose hereditária com porfiria cutânea tardia no mundo, mas até hoje apenas um estudo foi realizado no Brasil.\ud \ud OBJETIVOS:\ud Estudar a associação da porfiria cutânea tardia com as mutações C282Y e H63D do gene HFE. Identificar os fatores precipitantes (hepatite C, HIV, etilismo e estrógeno) e sua relação com as mutações HFE.\ud \ud MÉTODOS:\ud Estudo ambispectivo de 60 pacientes com porfiria cutânea tardia no período de 2003 a 2012. Investigou-se as sorologias para hepatite C, anti-HIV, histórico de etilismo e ingestão de estrógenos. As mutações HFE foram identificadas com PCR em tempo real.\ud \ud RESULTADOS:\ud A porfiria cutânea tardia predominou no sexo masculino e o etilismo foi o principal fator precipitante. A ingestão de estrógenos foi o único fator precipitante em 25% das mulheres. A hepatite C estava presente em 41,7%. Todos os pacientes com HIV (15,3%) apresentavam etilismo associado. A frequência dos alelos C282Y (p=0,0001) e H63D (p=0,0004) do gene HFE foi significativamente mais elevada nos pacientes com porfiria cutânea tardia em relação à população controle. As mutações HFE não apresentavam associação com os demais fatores precipitantes.\ud \ud CONCLUSÕES:\ud Etilismo, hepatite C e ingestão de estrógenos (em mulheres) são fatores precipitantes prevalentes na nossa população com porfiria cutânea tardia, entretanto a hemocromatose isoladamente também pode contribuir para o desencadeamento da porfiria cutânea tardia, o que torna a pesquisa das mutações HFE necessária nestes pacientes.Financial support: Fundação de Apoio à Pesquisa do Estado de São Paulo (Fapesp) - Nº do projeto: 2010/51781-4

Analysis of HFE And Non-HFE Gene Mutations in Brazilian Patients with Hemochromatosis

BACKGROUND: Approximately one-half of Brazilian patients with hereditary hemochromatosis (HH) are neither homozygous for the C282Y mutation nor compound heterozygous for the H63D and C282Y mutations that are associated with HH in Caucasians. Other mutations have been described in the HFE gene as well as in genes involved in iron metabolism, such as transferrin receptor 2 (TfR2) and ferroportin 1 (SCL40A1). AIMS: To evaluate the role of HFE, TfR2 and SCL40A1 mutations in Brazilian subjects with HH. PATIENTS AND METHODS: Nineteen male subjects (median age 42 [range: 20-72] years) with HH were evaluated using the Haemochromatosis StripAssay A®. This assay is capable of detecting twelve HFE mutations, which are V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y and Q283, four TfR2 mutations, which are E60X, M172K, Y250X, AVAQ594-597del, and two SCL40A1 mutations, which are N144H and V162del. RESULTS: In our cohort, nine (47%) patients were homozygous for the C282Y mutation, two (11%) were heterozygous for the H63D mutation, and one each (5%) was either heterozygous for C282Y or compound heterozygous for C282Y and H63D. No other mutations in the HFE, TfR2 or SCL40A1 genes were observed in the studied patients. CONCLUSIONS: One-third of Brazilian subjects with the classical phenotype of HH do not carry HFE or other mutations that are currently associated with the disease in Caucasians. This observation suggests a role for other yet unknown mutations in the aforementioned genes or in other genes involved in iron homeostasis in the pathogenesis of HH in Brazil

A imunoglobulina policlonal humana anti-antígeno de superfície da hepatite B reduz a freqüência da rejeição aguda após transplante de fígado

BACKGROUND: Use of polyclonal anti-hepatitis B surface antigen immunoglobulin (HBIg) has been shown to reduce hepatitis B virus (HBV) recurrence after liver transplantation (LT) and to decrease the frequency of acute cellular rejection (ACR). However, the protective role of HBIg against ACR remains controversial, since HBV infection has been also associated with a lower incidence of ACR. AIM: To assess the relationship between HBIg immunoprophylaxis and the incidence of rejection after LT. METHODS: 260 patients (158 males, 43 ± 14 years old) submitted to LT were retrospectively evaluated and divided into three groups, according to the presence of HBsAg and the use of HBIg. Group I was comprised of HBsAg-positive patients (n = 12) that received HBIg for more than 6 months. Group II was comprised of HBsAg-positive patients that historically have not received HBIg or have been treated irregularly for less than 3 months (n = 10). Group III was composed of 238 HBsAg-negative subjects that have not received HBIg. RESULTS: HBIg-treated patients (group I) had significantly less ACR episodes, when compared to group II and III. No differences between groups II and III were observed. CONCLUSIONS: Long-term HBIg administration contributes independently to reduce the number of ACR episodes after LT.INTRODUÇÃO: O emprego da imunoglobulina policlonal anti-antígeno de superfície da hepatite B (HBIg) tem reduzido a recorrência da hepatite B após transplante hepático (TH), assim como também a freqüência de rejeição celular aguda (RCA). No entanto, o papel protetor da HBIg contra a RCA permanece controverso, pois a própria infecção por vírus B foi também associada a menor incidência de RCA. OBJETIVOS: Verificar a relação entre HBIg e a freqüência de RCA após TH. MÉTODOS: 260 pacientes (158 do sexo masculino, com 43 ± 14 anos) submetidos a TH foram avaliados, retrospectivamente, e divididos em três grupos de acordo com a presença de AgHBs e uso de HBIg. O grupo I foi constituído por 12 pacientes com AgHBs que receberam HBIg por mais de 6 meses; o grupo II foi formado por 10 pacientes com AgHBs que não receberam HBIg regularmente; o grupo III foi composto por 238 indivíduos sem AgHBs que não receberam HBIg. RESULTADOS: Nos pacientes do grupo I houve freqüência significantemente menor de episódios de RCA, em comparação ao que se observou nos grupos II e III. Nenhuma diferença ocorreu entre os grupos II e III. CONCLUSÕES: A administração profilática de HBIg contribui independentemente para reduzir a freqüência dos episódios de RCA após a realização de TH

Histological remission of autoimmune hepatitis after the addition of allopurinol and azathioprine dose reduction

The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Many patients preferentially metabolize thiopurines to 6-methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6-thioguanine, the active immunosuppressive metabolite. The addition of allopurinol shifts the metabolism of thiopurine towards 6-thioguanine, improving the immunosuppressive effect. We present the case of a 51-year-old female with autoimmune hepatitis who had a biochemical response after azathioprine and prednisone treatment without histological remission, and who preferentially shunted to 6-MMP. After the addition of allopurinol, the patient’s 6-thioguanine levels increased, and she reached histological remission with a reduction of 67% of the original dose of azathioprine. The patient did not develop clinical manifestations as a consequence of her increased immunosuppressive state. We also review the relevant literature related to this issue. In conclusion, the addition of allopurinol to thiopurine seems to be an option for those patients who do not reach histological remission and who have a skewed thiopurine metabolite profil

Doença de Wilson no sul do Brasil: correlação genotípica-fenotípica\ud e a descrição de duas novas mutações no gene ATP7B

OBJECTIVE:\ud \ud Wilson's disease (WD) is an inborn error of metabolism caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in a group of patients living in southern Brazil.\ud \ud METHODS:\ud \ud 36 WD subjects were studied and classified according to their clinical and epidemiological data. In 23 subjects the ATP7B gene was analyzed.\ud \ud RESULTS:\ud \ud Fourteen distinct mutations were detected in at least one of the alleles. The c.3207C>A substitution at exon 14 was the most common mutation (allelic frequency=37.1%) followed by the c.3402delC at exon 15 (allelic frequency=11.4%). The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon 20 are being reported for the first time.\ud \ud CONCLUSION:\ud \ud The c.3207C>A substitution at exon 14, was the most common mutation, with an allelic frequency of 37.1%. This mutation is the most common mutation described in Europe.OBJETIVO:\ud \ud A doença de Wilson (DW) é um erro inato do metabolismo causado por abnormalidades no gene ATP7B, que codifica uma proteína transportadora de cobre. Neste estudo, avaliamos as mutações do gene ATP7B em um grupo de pacientes do sul do Brasil.\ud \ud MÉTODOS:\ud \ud Foram estudados 36 pacientes com DW e classificados do ponto de vista clínico e epidemiológico. Em 23 pacientes, o gene ATP7B foi analisado.\ud \ud RESULTADOS:\ud \ud A substituição c.3207C>A no éxon 14 foi a mutação mais comum seguida pela mutação c.3402delC no éxon 15 . A mutação c.2018-2030del13 no éxon 7 e a c.4093InsT no éxon 20 são relatadas pela primeira vez na literatura.\ud \ud CONCLUSÃO:\ud \ud A mutação do gene ATP7B, com a substituição c.3207C>A no éxon 14 foi a mais frequente. Esta mutação é a mais comumente encontrada em pacientes europeus

Histological remission of autoimmune hepatitis after the addition of allopurinol and azathioprine dose reduction

The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Many patients preferentially metabolize thiopurines to 6-methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6-thioguanine, the active immunosuppressive metabolite. The addition of allopurinol shifts the metabolism of thiopurine towards 6-thioguanine, improving the immunosuppressive effect. We present the case of a 51-year-old female with autoimmune hepatitis who had a biochemical response after azathioprine and prednisone treatment without histological remission, and who preferentially shunted to 6-MMP. After the addition of allopurinol, the patient’s 6-thioguanine levels increased, and she reached histological remission with a reduction of 67% of the original dose of azathioprine. The patient did not develop clinical manifestations as a consequence of her increased immunosuppressive state. We also review the relevant literature related to this issue. In conclusion, the addition of allopurinol to thiopurine seems to be an option for those patients who do not reach histological remission and who have a skewed thiopurine metabolite profil

Antineutrophil cytoplasmic antibody profiles differ according to type of primary sclerosing cholangitis and autoimmune hepatitis

OBJECTIVES: To determine the frequency of the antineutrophil cytoplasmic antibodies (ANCA), antiproteinase-3 and antimyeloperoxidase, in primary sclerosing cholangitis (PSC) with or without inflammatory bowel disease (IBD+ or IBD-) and in different types of autoimmune hepatitis (AIH). Additionally, to verify the agreement between ANCA patterns by indirect immunofluorescence and their antigenic specificities by ELISA. METHODS: For this study, 249 patients were enrolled (42 PSC/IBD+; 33 PSC/IBD-; 31 AIH type-1; 30 AIH type-2; 31 AIH type-3; 52 primary biliary cirrhosis; 30 healthy controls) whose serum samples were tested for ANCA autoantibodies. RESULTS: There were fewer female subjects in the PSC/IBD- group (p=0.034). Atypical perinuclear-ANCA was detected more frequently in PSC/IBD+ patients than in PSC/IBD- patients (p=0.005), and was significantly more frequent in type-1 (po0.001) and type-3 AIH (p=0.012) than in type-2 AIH. Proteinase-3-ANCA was detected in 25 samples (only one with cytoplasmic-ANCA pattern), and more frequently in PSC/IBD+ than in PSC/IBDpatients (p=0.025). Myeloperoxidase-ANCA was identified in eight samples (none with the perinuclear-ANCA pattern). Among the 62 reactive samples for atypical perinuclear-ANCA, 13 had antigenic specific reactions for proteinase-3 and myeloperoxidase. CONCLUSIONS: PSC/IBD+ differed from PSC/IBD- in terms of sex and proteinase 3-ANCA and atypical perinuclear-ANCA reactivity, the latter of which was more frequently detected in type-1 and type-3 AIH than in type-2 AIH. There was no agreement between ANCA patterns and antigenic specificities in IBD and autoimmune liver diseases, which reinforces the need for proteinase-3 and myeloperoxidase antibody testing