Lack of evidence for the pathogenic role of iron and HFE gene mutations in Brazilian patients with nonalcoholic steatohepatitis

The hypothesis of the role of iron overload associated with HFE gene mutations in the pathogenesis of nonalcoholic steatohepatitis (NASH) has been raised in recent years. In the present study, biochemical and histopathological evidence of iron overload and HFE mutations was investigated in NASH patients. Thirty-two NASH patients, 19 females (59 percent), average 49.2 years, 72 percent Caucasians, 12 percent Mulattoes and 12 percent Asians, were submitted to serum aminotransferase and iron profile determinations. Liver biopsies were analyzed for necroinflammatory activity, architectural damage and iron deposition. In 31 of the patients, C282Y and H63D mutations were tested by PCR-RFLP. Alanine aminotransferase levels were increased in 30 patients, 2.42 + or - 1.12 times the upper normal limit on average. Serum iron concentration, transferrin saturation and ferritin averages were 99.4 + or - 31.3 g/dl, 33.1 + or - 12.7 percent and 219.8 + or - 163.8 æg/dl, respectively, corresponding to normal values in 93.5, 68.7 and 78.1 percent of the patients. Hepatic siderosis was observed in three patients and was not associated with architectural damage (P = 0.53) or with necroinflammatory activity (P = 0.27). The allelic frequencies (N = 31) found were 1.6 and 14.1 percent for C282Y and H63D, respectively, which were compatible with those described for the local population. In conclusion, no evidence of an association of hepatic iron overload and HFE mutations with NASH was found. Brazilian NASH patients comprise a heterogeneous group with many associated conditions such as hyperinsulinism, environmental hepatotoxin exposure and drugs, but not hepatic iron overload, and their disease susceptibility could be related to genetic and environmental features other than HFE mutations

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53 percent) were homozygous and one (7 percent) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil

Disappearance of hepatitis B surface antigen in chronic type B hepatitis after clinical and laboratorial relapse produced by abrupt withdrawal of immunossupressive drugs.

Paciente com hepatite cronica ativa por virus B foi submetido a tratamento imunossupressor com prednisolona e azatioprina.Contudo, tal medicacao foi bruscamente interrompida, em virtude de sangramento por gastrite erosiva hemorragica. Observou-se, em seguida, grave deterioracao do estado do paciente, com aparecimento de ictericia, ascite e sinais de encefalopatia hepatica. Concomitantemente a melhora do quadro clinico, observou-se desaparecimento do antigeno de superficie e do antigeno da hepatite B. O anti-HBs surgiu dez meses apos a recrudescencia

Activity of chronic hepatitis correlation of clinical, biochemical and histological parameters in 32 cases.

Os Autores estudaram 32 casos de hepatites cronicas com diversos graus de atividade clinica, bioquimica e histologica. A etiologia foi predominantemente viral. Quinze parametros histologicos foram semiquantificados, pesquisando-se posteriormente, correlacao entre os graus obtidos e os valores sericos de ALT, AST, Gama-GT, bilirrubina total e gamaglobulina. Dos parametros histologicos, a proliferacao de ductos biliares e os plasmocitos nao se mostraram uteis para esta analise. Os niveis de bilirrubina total apresentam correlacao estatisticamente significante com 11 variaveis histologicas. Ambas as aminotransferases (ALT e AST) correlacionaram-se com a impressao geral de atividade histologica, sendo que a AST tambem se correlacionou com o grau de expansao portal e de necrose "em saco bocados". A ausencia de correlacoes significantes com gamaglobulina pode se dever a inclusao, neste estudo, de casos de hepatite cronica persistente e a ausencia de hepatites cronicas autoimunes

Reuniao anatomo-clinica do Instituto da Crianca. / Anatomo-clinical meeting of the Instituto da Crianca

Os autores descrevem o caso de uma crianca de 3 anos e 8 meses de idade com sinais e sintomas de hipertensao portal. A necropsia revelou ser a causa uma doenca veno-oclusiva hepatica com comprometimentos, em extensao, das veias supra-hepaticas. A crianca faleceu 7 meses apos a internacao. E comentado o diagnostico diferencial com a Sindrome de Budd-Chiari, bem como os aspectos rediologicos dos quadros com hipertensao portal

Tumores germinativos dos testiculos. / Germ cell tumors of the testis

Os autores analisam 21 casos de tumores de celulas germinativas dos testiculos, com relacao aos dados clinicos e anatomopatologicos dos tumores primarios e metastases Dao especial destaque a avaliacao de fatores relacionados a etiologia e efetuam estudo semiquantitativo de caracteristicas histologicas, tais como anaplasia, mitoses, inflamacao, necrose/hemorragia, invasao vascular e invasao do cordao espermatico, alem de registrarem os padroes histologicos das metastases