-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 fi ndings 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 infl ammatory activity, presence of fi brosis, 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 infl ammatory activity, nor with the presence of fi brosis 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 fi brosis. Conclusions -The fi ndings 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. HEADINGS -Hemochromatosis. Fatty liver. Liver cirrhosis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a major disorder in patients with persistent changes in aminotransferase activity who test negative for viral markers and autoantibodies. Although NASH has been correlated with obesity, no study has been carried out exclusively with nondiabetic obese patients.OBJECTIVES: To evaluate the occurrence of NASH in obese patients without diabetes mellitus and to assess the severity of histological involvement of the liver.PATIENTS AND METHODS: Serum aminotransferase levels were evaluated in 912 obese patients seen at an outpatient clinic in Porto Alegre, Brazil, from 1997 to 1999. Sixty-eight patients were found to have altered aminotransferase levels in more than one test. Thirty-five patients were excluded due to the presence of diabetes mellitus (n=12), the presence of viral markers (n=11), alcohol consumption (n=8) and the use of hepatotoxic drugs (n=4). NASH was diagnosed when histological findings revealed macrovesicular steatosis associated with lobular inflammatory infiltrate and hepatocellular injury.RESULTS: Of the 912 obese patients studied, 33 patients with altered aminotransferase levels underwent liver biopsy. Four patients were excluded because they had steatosis only; the remaining 29 patients (3.18%) fulfilled the diagnostic criteria established for NASH. The mean age of the 29 patients was 42.2±11.9 years; 65.52% of the patients were women. Grading of histological findings revealed mild disease in 58.6% of cases; important proliferation of fibrous tissue was absent in most cases.CONCLUSIONS: NASH is a common disease among nondiabetic obese patients with altered aminotransferase levels, and it usually manifests as a mild clinical condition, although more severe lesions may be observed.

RESUMO -Contexto -Ainda existem vários aspectos desconhecidos a respeito da esteatohepatite não-alcoólica, principalmente em relação à fisiopatologia e ao seu tratamento medicamentoso. Dessa forma, os modelos experimentais são importante para o melhor entendimento dessa doença, bem como para a avaliação do efeito das drogas. Objetivo -Desenvolver um modelo experimental de esteatohepatite não-alcoólica a partir do uso de dieta deficiente em metionina e colina. Métodos -Foram utilizados 50 ratos machos da linhagem Wistar. A dieta deficiente em metionina e colina foi processada de forma artesanal. Um grupo de 40 animais recebeu a dieta durante 90 dias e utilizou-se um grupo controle com 10 ratos que recebeu ração padronizada pelo mesmo período. Após, os animais foram mortos por decapitação e foi realizada laparotomia com hepatectomia total e preparo do material para análise macroscópica e histológica. O nível de significância foi α = 0,05. Resultados -Os ratos que receberam a dieta apresentaram perda significativa de peso, com achados de desnutrição e todos mostraram, pelo menos, algum grau de esteatose macrovesicular. O diagnóstico de esteatohepatite não-alcoólica foi realizado em 27 (70%) dos 39 ratos que receberam a dieta. Nenhum dos 10 ratos que recebeu ração apresentou alterações histológicas. Conclusão -A dieta com restrição de metionina e colina desenvolvida apresenta índices elevados de indução de esteatose e esteatohepatite em modelo animal com baixo custo. DESCRITORES -Fígado gorduroso. Dieta. Metionina, deficiência. Deficiência de colina. Ratos. INTRODuçÃOA esteatohepatite não-alcóolica (EHNA) é caracterizada por acúmulo de gordura no fígado associado a graus variáveis de inflamação e fibrose. Esta doença apresenta forte associação com obesidade, sexo feminino e diabete melito (DM) (5,30,31,48) . Atualmente, no ocidente, a EHNA tem sido considerada ora a segunda (12) , ora a terceira (9) doença hepática mais comum em pacientes de ambulatório. Em nosso meio, ao serem avaliados prospectivamente, 912 indivíduos obesos, sem DM associado, em ambulatório de nutrição, foi possível determinar, pela primeira vez em estudo populacional e não de uma série de casos, prevalência de esteatohepatite não-alcoólica da ordem de 3,18% (56) . Essa prevalência, no entanto, é subestimada, uma vez que só foram avaliados os pacientes com alterações de aminotransferases.A despeito de apresentar alta prevalência na população, a história natural de EHNA ainda é pouco estudada. Atualmente, acredita-se que a EHNA possa evoluir para cirrose e carcinoma hepatocelular (CHC), enquanto a esteatose isolada não costuma apresentar esta evolução. Ressalta-se existirem poucos estudos prospectivos na literatura, com biopsias sequenciais, em pacientes com EHNA com o intuito de avaliar a progressão da doença (5,25,43) . O reconhecimento do seu potencial evolutivo e a sua alta prevalência são os principais motivos que despertam o interesse da comunidade científica em relação ao seu estudo (4,5,8,9,13,25,30,32,43,44,48,49,50,51,53,55) . A respeito...

-Context -No effective treatment is available for nonalcoholic steatohepatitis in nowadays. Objectives -To develop a model of nonalcoholic steatohepatitis induced by a methionine and choline deficient diet, as well as to evaluate the role of metformin, vitamin E and simvastatin in the nonalcoholic steatohepatitis progression. Methods -The study analyzed prospectively 50 Wistar rats for a 90-day period and divided them into five groups of 10 rats. One group was given standard rat diet and the others received the methionine and choline deficient diet. Among the four groups that received this diet, one received saline 0,9% and the others received metformin, vitamin E or simvastatin. After the study period, the animals were sacrificed and their blood was collected for biochemical analysis. The livers were removed for lipoperoxidation analysis and for the histological examinations. Results -The methionine and choline deficient diet was able to induce steatosis in 100% of the animals and nonalcoholic steatohepatitis in 27 (69.2%). The alanine aminotransferase levels were significantly higher in the simvastatin group. The aspartate aminotransferase levels were also higher in the simvastatin group, but were statistically significant only in relation to the standard diet group. When lipoperoxidation values were compared, the groups that received standard rat diet and methionine and choline deficient with vitamin E presented significantly lower rates than the others. The presence of fibrosis was significantly smaller in the group receiving vitamin E. Conclusions -The diet used was able to induce steatosis and nonalcoholic steatohepatitis. Besides vitamin E showed to reduce the liver oxidative stress, as well as the fibrosis development. HEADINGS -Vitamin E. Fatty liver. Rats.

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