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: 10.76). 01/2011; 106(1):71-7. DOI: 10.1038/ajg.2010.299
Source: PubMed


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.

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Available from: Naser Ahmadi, Feb 25, 2015
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    • "They concluded that the vitamins treatment achieved an improvement of hepatic fibrosis[39]. Foster et al. suggested that 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[40]. In contrast, another two trials suggested that the combination of vitamin C and vitamin E supplementation did not achieve a better treatment effect than lifestyle intervention in children with NAFLD[41,42]. "
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    ABSTRACT: Background: Non-alcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disease all over the world. The objective of this study was to evaluate the association between dietary vitamin C intake and NAFLD. Method: Subjects were diagnosed with NAFLD by abdominal ultrasound examination and the consumption of alcohol was less than 40g/day for men or less than 20g/day for women. Vitamin C intake was classified into four categories according to the quartile distribution in the study population: ≤74.80 mg/day, 74.81-110.15 mg/day, 110.16-146.06 mg/day, and ≥146.07 mg/day. The energy and multi-variable adjusted odds ratio (OR), as well as their corresponding 95% confidence interval (CI), were used to determine the relationship between dietary vitamin C intake and NAFLD through logistic regression. Result: The present cross-sectional study included 3471 subjects. A significant inverse association between dietary vitamin C intake and NAFLD was observed in the energy-adjusted and the multivariable model. The multivariable adjusted ORs (95%CI) for NAFLD were 0.69 (95%CI: 0.54-0.89), 0.93 (95%CI: 0.72-1.20), and 0.71 (95%CI: 0.53-0.95) in the second, third and fourth dietary vitamin C intake quartiles, respectively, compared with the lowest (first) quartile. The relative odds of NAFLD was decreased by 0.71 times in the fourth quartile of dietary vitamin C intake compared with the lowest quartile. After stratifying data by sex or the status of obesity, the inverse association remained valid in the male population or non-obesity population, but not in the female population or obesity population. Conclusion: There might be a moderate inverse association between dietary vitamin C intake and NAFLD in middle-aged and older adults, especially for the male population and non-obesity population.
    Full-text · Article · Jan 2016 · PLoS ONE
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    • "Statins have been tested in NAFLD treatment only in either underpowered, or not controlled, or in studies lacking histological assessment of liver damage, which still is the gold standard to assess the prognosis of the disease [23]. In these studies, statins were well tolerated and reduced cardiovascular risk [20] [24], but results on liver-related outcomes were not conclusive [25] [26] [27] [28] [29] [30]. Furthermore, randomized trials testing the effect of statins in individuals with NASH would be difficult to design because these patients often require statin treatment to reduce cardiovascular risk [31] [32]. "

    Full-text · Article · Oct 2015 · Journal of Hepatology
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    • "Therapeutic agents for the treatment of dyslipidemia can be used in NAFLD as well as in cardiometabolic disorders, because lipotoxicity is a common pathophysiology of the two diseases. Atorvastatin reduced radiological and biochemical markers of steatosis when used alone [89] or in combination with antioxidants [53]. Another lipid-lowering drug, ezetimibe, yielded improvement of liver histology [89]. "
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is a chronic condition characterized by fat accumulation combined with low-grade inflammation in the liver. A large body of clinical and experimental data shows that increased flux of free fatty acids from increased visceral adipose tissue can lead to NAFLD related with insulin resistance. Thus, individuals with obesity, insulin resistance, and dyslipidemia are at the greatest risk of developing NAFLD. Conversely, NAFLD is one of the phenotypes of insulin resistance or metabolic syndrome. Many researchers have discovered a close association between NAFLD and insulin resistance, and focused on the role of NAFLD in the development of type 2 diabetes. Further, substantial evidence has suggested the association between NAFLD and cardiovascular disease (CVD). In the current review, we provide a plausible mechanistic link between NAFLD and CVD and the potential of the former as a therapeutic target based on pathophysiology. We also discuss in detail about the role of insulin resistance, oxidative stress, low-grade inflammation, abnormal lipid metabolism, gut microbiota, changes of biomarkers, and genetic predisposition in the pathological linking between NAFLD and cardiometabolic disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Aug 2015 · International journal of cardiology
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