Background and aims: Insulin resistance and cytokine production are key mechanisms leading to fatty
change in the liver and may produce nonalcoholic steatohepatitis (NASH). Oxidative stress may also
contribute to clinical progression from simple fatty liver (FL) to NASH. A therapy for insulin resistance
and antioxidant has been applied to treat NASH, yet these treatments are not fully established. In the
present study, we have evaluated whether an antioxidant agent, glutathione, prevents the development
of NASH from FL.
Materials and methods: Five patients with FL and 10 with NASH were enrolled in the study. Three
hundred milligrams per day of glutathione was given orally to patients with nonalcoholic fatty liver
disease (NAFLD) every day, and an oxidative stress marker and biochemical tests were analyzed before
treatment and 1 and 3 months after starting the treatment. We measured serum levels of 8-hydroxy-
2-deoxyguanosine (8-OHdG) and gamma-glutamyltranspeptidase (GGT). Immunohistochemistry for
glutathione was performed on formalin fixed liver specimens obtained from liver biopsies.
Results: Before treatment, the NASH group had higher serum 8-OHdG and lower serum glutathione
levels than the FL group. Immunohistochemistry revealed that a strong expression of glutathione was
observed in zone 3 in both NASH and FL before treatment. Serum levels of alanine transaminase and
8-OHdG were significantly decreased after treatment in the NASH group. Gamma-glutamyltranspeptidase
was decreased after treatment, although the decrease was statistically not significant.
Discussion: The present pilot study demonstrated that antioxidant therapy with glutathione may reduce
the pathological oxidative stress in the liver in NASH, preventing the progression from NAFLD to NASH.
Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the Figs 4A and B: Immunohistochemical staining of glutathione in liver tissues. Immunoreactivity glutathione was strongly expressed in the cytoplasm of hepatocytes in an FL tissue; (A) as well as in a NASH tissue; (B) in the liver lobule zones 3 (× 200). There were no differences in the localization, but immunoreactivity of glutathione expression is stronger in an FL tissue than in an NASH tissue; and (C) Central vein A B Makoto Irie et al 18 American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012 Jun;55(6):2005-2023
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