Atorvastatin and Antioxidants for the Treatment of Nonalcoholic Fatty Liver Disease: The St Francis Heart Study Randomized Clinical Trial

Department of Medicine, University of California, Los Angeles, California 90095, USA.
The American Journal of Gastroenterology (Impact Factor: 9.21). 01/2011; 106(1):71-7. DOI: 10.1038/ajg.2010.299
Source: PubMed

ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is defined as the spectrum of benign fatty liver to necroinflammation and fibrosis. Its prevalence has been found to be as high as 39%. It is estimated that up to 15% of those affected will go on to have progressive liver disease. Currently, there is no proven therapy for NAFLD. In this study, we aim to determine whether statin therapy may be an effective treatment for NAFLD and identify independent predictors of NAFLD.
In all, 1,005 men and women, aged 50-70 years were randomized to receive either a daily combination of atorvastatin 20 mg, vitamin C 1 g, and vitamin E 1,000 IU vs. matching placebo, as part of the St Francis Heart Study randomized clinical trial. Liver to spleen (LS) ratios were calculated on 455 subjects with available computed tomography scans performed at baseline and follow-up to determine NAFLD prevalence. Baseline and final LS ratios were compared within treatment groups, and results were compared between the treatment and placebo groups using univariate and multivariate analyses. Mean duration of follow-up was 3.6 years.
There were 80 patients with NAFLD at baseline. We identified baseline triglyceride levels (odds ratio (OR)=1.003, P<0.001) and body mass index (OR=0.10, P<0.001) as independent correlates of NAFLD. Treatment with atorvastatin combined with vitamins E and C significantly reduced the odds of NAFLD at the end of follow-up, 70 vs. 34% (OR=0.29, P<0.001).
In conclusion, atorvastatin 20 mg combined with vitamins C and E is effective in reducing the odds of having hepatic steatosis by 71% in healthy individuals with NAFLD at baseline after 4 years of active therapy.

Download full-text


Available from: Naser Ahmadi, Feb 25, 2015
  • Source
    • "Foster et al. [91] Double-blinded randomized placebo-controlled trial Mean follow-up 3.6 year 80 NAFLD Atorvastatin 20 mg Well tolerated and effective in NAFLD Pramfalk et al. [92] Double-blinded randomized placebo-controlled trial Mean follow-up 4.0 weeks 19 NAFLD "
    [Show abstract] [Hide abstract]
    ABSTRACT: The clinical benefits of statins are strongly related to their low density lipoprotein cholesterol (LDL-C) lowering properties. However, considering that the pharmacological target of statins, the 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase, is one of the upstream enzyme of the mevalonate pathway, its inhibition may determine a substantial impoverishment of additional lipid moieties required for a proper cellular function. From this hypothesis, several experimental and clinical evidence have been reported indicating additional effects of statins beyond the LDL-C lowering, in particular anti-inflammatory and immunomodulatory effects. Thus statin therapy, indicated for hyperlipidemic patients for primary and secondary prevention of coronary heart disease (CHD) have begun to be considered effective in other diseases not necessarily linked to altered lipid profile. In the present review we summarized the current clinical evidence of the efficacy and safety profile of statins in a variety of diseases, such as rheumatoid arthritis, venous thromboembolism, liver diseases, polycystic ovary syndrome, and age-related macular degeneration. As discussed in the review, pending large, well designed, randomized trials, it is reasonable to conclude that there is no definitive evidence for the use of statins in the aforementioned diseases.
    Pharmacological Research 02/2014; 88. DOI:10.1016/j.phrs.2014.02.003 · 3.98 Impact Factor
  • Source
    • "NAFLD patients were randomized to receive vitamin E (600 IU/day) and vitamin C (500 mg/day) or ursodeoxycholic acid (10 mg/kg/day) after 6 months, VE plus VC group can improve the ALT and AST levels more effectively , although the difference is not obvious [29]. Foster [30] evaluated the effective of simvastatin (20 mg/day) plus antioxidants VE (1000 IU daily) VC (1 g daily) for four years on 80 NAFLD patients diagnosed by CT, and found it significantly improved steatosis compared with placebo, but ALT, inflammation and liver fibrosis levels were not evaluated. "
    International Journal of Clinical Medicine 01/2014; 05(03):87-92. DOI:10.4236/ijcm.2014.53016
  • Source
    • "The subsequent phosphorylation by these kinases leads to eventual ubiquitination and proteasome-dependent degradation of IκB, releasing the latent dimeric transcription factor to the nucleus, where it binds to promoter sites for gene transcription (DiDonato et al., 1997; Nakano et al., 2006; Carlsen et al., 2004; Blackwell and Christman, 1997). Atorvastatin, a hydrophobic statin is indicated for the treatment of dyslipidemia, specifically hypercholesterolemia, combined hyperlipidemia and non-alcoholic fatty liver disease with high cardiovascular risk factors (Lupattelli et al., 2012; Malhotra and Goa, 2001; Lea and McTavish, 1997; Foster et al., 2011; Chalasani, 2005). The antioxidant and anti-inflammatory effects of this compound have well studied (Stoll et al., 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: AIMS: The present study addressed to evaluate a comparative and combined hepatoprotective effect of atorvastatin (AS) and ferulic acid (F) against high fat diet (HFD) induced oxidative stress in terms of hyperlipidemia, anti oxidative status, lipid peroxidation and inflammation. MAIN METHODS: Male Swiss albino mice were given a diet containing high fat (H) (23.9% wt/wt), supplemented with AS (10 mg/kg) or F (100 mg/kg) and both (10 and 100 mg/kg) for 8 weeks. The control mice (C) were fed with normal diet. KEY FINDINGS: The H mice exhibited increased body weight; hyperlipidemia; serum level of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6); hepatic lipid profile; lipid accumulation; reactive oxygen species (ROS) of hepatocytes, lipid peroxidation and liver antioxidant capacity was decreased. Immunofluorescent and Western blot assay revealed activation of nuclear factor kappa B (NF-κB) signalling pathway. Addition of F or AS and both in the diet significantly counteracted HFD induced body weight gain; hyperlipidemia; TNF-α, IL-6; hepatic lipid profile; fatty infiltration; NF-κB signalling pathway; ROS; lipid peroxidation and moreover elevated levels of hepatic antioxidant enzymes activity were observed. SIGNIFICANCE: Simultaneous treatment with AS, F and their combination protected against HFD induced weight gain and oxidative stress. The protection may be attributed to the hypolipidemic and free radical scavenging activity of AS or F and their combination. This study illustrates that AS and F has relatively similar hypolipidemic, antioxidative, anti inflammatory actions and the AS+F combination along with HFD has shown outstanding effects as compared to other treated groups.
    Life sciences 04/2013; 92(17-19). DOI:10.1016/j.lfs.2013.03.015 · 2.30 Impact Factor
Show more