Cytokines and NASH: A pilot study of the effects of lifestyle modification and vitamin E

Abstract

There are few data evaluating plasma and/or peripheral blood monocyte cytokine concentrations/production or attempts to manipulate proinflammatory cytokines in nonalcoholic steatohepatitis (NASH). A pilot project in a general clinical research center evaluated the effects of a step 1 American Heart Association diet plus aerobic exercise with or without 800 IU of vitamin E daily on cytokine profiles and liver enzyme levels in 16 patients with biopsy-proven NASH. Biochemical assessment of liver function, lipid profiles, and body mass index significantly improved during the first 6 weeks of therapy and remained stable during the following 6 weeks. Plasma hyaluronic acid (HA) concentrations decreased in parallel with weight loss. Plasma tumor necrosis factor (TNF) concentrations were significantly elevated in patients with NASH and similar to patients with stable alcoholic cirrhosis but not as elevated as in patients with acute alcoholic steatohepatitis (AH). Although plasma TNF, interleukin 8 (IL-8), and IL-6 concentrations were all significantly elevated compared with control values, only plasma IL-6 levels significantly decreased with therapy. Peripheral blood monocyte TNF, IL-8, and IL-6 production was significantly elevated in patients with NASH but did not significantly decrease. Independent effects of vitamin E were not observed in this small sample. In conclusion, patients with NASH have dysregulated cytokine metabolism similar to, but less pronounced than abnormalities documented in AH. Cytokine values generally did not decrease significantly with weight loss with or without vitamin E over the duration of the study. Lifestyle modifications (low-fat diet and exercise) were associated with improvement in liver enzymes, cholesterol, and plasma HA levels in patients with NASH, whereas the level of vitamin E supplementation used in this short-term pilot study provided no apparent added benefit. (HEPATOLOGY 2003;38:413-419.)

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

“…Many studies indicate that lifestyle modification may reduce aminotransferases and improve hepatic steatosis when measured either by ultrasound [73][74][75][76][77][78][79][80] 95 However, these early studies were inconclusive as a result of being small, largely uncontrolled and few using histology as the primary endpoint. More recent uncontrolled studies also showed an improvement in aminotransferases and hepatic steatosis on histology with lifestyle modification.…”

Prevalence of COPD in Primary Care Clinics: Correlation with Non-Respiratory Diseases

“…P r e v a l e n c e o f COP D a n d De t a i l s o f L i v e r Di s e a s e s tivation and mRNA stabilization (27). An elevation of the serum level of IL-8 has also been observed in patients with nonalcoholic steatohepatitis (30) and those with alcoholic liver disease (31) (1,32). It has been reported that the exhaled NO level is increased in liver cirrhosis (33,34), and the expression of pulmonary vascular NO synthase (NOS) is increased in hepatopulmonary syndrome (35)(36)(37) …”

Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis

“…1,2 Although the causes of NASH are not well defined and several therapies including diet, 3 antioxidants, 4 and approaches that improve insulin resistance 5 have been tried, no commonly accepted therapeutic protocol has yet been established. Recent studies have demonstrated a crucial role of angiotensin II in the pathogenesis of hepatic fibrosis, 6 and this peptide has been shown to enhance insulin resistance and tissue iron deposition.…”