The vitamin E reduces liver lipoperoxidation and fibrosis in a model of nonalcoholic steatohepatitis.

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.

[Model of experimental nonalcoholic steatohepatitis from use of methionine and choline deficient diet]. / Modelo experimental de esteatohepatite não-alcoólica com dieta deficiente em metionina e colina.

CONTEXT: There are still many unknown aspects about nonalcoholic steatohepatitis, especially regarding its pathophysiology and pharmacological treatment. Thus, experimental models are important for a better understanding of this disease and the evaluation of the effects of drugs. OBJECTIVE: To develop a model of experimental nonalcoholic steatohepatitis from use of methionine and choline deficient diet. METHODS: Fifty Wistar male rats were studied. A methionine and choline deficient diet has been processed in a craft. A group of 40 animals received the deficient diet for 90 days, and a group of 10 rats (control group) received the standardized ration in the same period. After, the animals were killed by decapitation, and laparotomy was performed. Hepatectomy was performed and the liver was studied by macroscopy and microscopy. The level of significance considered was of 0,05. RESULTS: The rats that received the deficient diet showed significant loss of weight with findings from malnutrition and all of them had at least some degree of macrovesicular steatosis. The diagnosis of nonalcoholic steatohepatitis was performed in 27 (70%) of the 39 rats that received this deficient diet (1 rat died during the study). None of the 10 rats that received the standardized diet had histological abnormalities. CONCLUSION: The diet restricted in methionine and choline induced steatosis and steatohepatitis in an animal model with low cost.

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.

Nonalcoholic steatohepatitis in nondiabetic obese patients.

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.