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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    • "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.
    International journal of cardiology 08/2015; 201:408-414. DOI:10.1016/j.ijcard.2015.08.107 · 4.04 Impact Factor
    • "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]. "
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of elevated transaminase levels and affects approximately one third of the general population. Patients with NAFLD are at increased risk for cardiovascular events, which represent the leading cause of death in this population. We discuss the safety and efficacy of statins in this population. We reviewed the most recent literature on the safety of statins in patients with NAFLD and on their effects on liver histology and cardiovascular events. It appears that statins can be safely administered to patients with NAFLD, including those with elevated transaminase levels (<3 times the upper limit of normal). Post-hoc analyses of randomized controlled trials also suggest that statins might reduce cardiovascular morbidity in this population. On the other hand, there are few and controversial data on the effects of statins on liver histology in patients with NAFLD. Statins appear to be safe and might also reduce cardiovascular events in patients with NAFLD. Ongoing and future studies will clarify whether statins might also have a role in the treatment of NAFLD. Copyright © 2015. Published by Elsevier Inc.
    Metabolism: clinical and experimental 07/2015; 64(10). DOI:10.1016/j.metabol.2015.07.003 · 3.89 Impact Factor
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    • "It seems to be more logical to use combination therapy in managing these patients because NAFLD pathogenesis occurs in multiple steps. The beneficial effect of combination therapy has been observed in several adult trials.[25262728] The Nobili et al., trials used a combination of vitamin E and vitamin C, both of which acted primarily as antioxidants. "
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    ABSTRACT: Background and Aims: To systemically evaluate the efficacy of adjuvant vitamin E on the outcomes of nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH) in children. Materials and Methods: We searched MEDLINE, PUBMED, EMBASE, the Cochrane Central Register Controlled Trials, and the Cochrane Database of Systematic Reviews over the period between January 1980 and September 2012 for the studies that examined the role of adjuvant vitamin E given at any dose or duration, alone or in combination with other interventions, on the outcome of pediatric NAFLD. The outcomes are alanine aminotransferase (ALT) normalization and histological improvement. Results: Five randomized trials were eligible to be included in our analysis, with a total of 270 participants. There was no statistically significant difference in the effect of adjuvant vitamin E on normalizing serum ALT [risk ratio (RR) =1.18, confidence interval (CI) =0.92-1.53, P = 0.77 for heterogeneity, I2 = 0%]. Sensitivity analysis showed that using higher doses of vitamin E, a longer duration of therapy or adding vitamin C did not change the effect on the measured outcome. Only two studies looked at histological changes as an outcome. We observed substantial heterogeneity between the two studies. Conclusions: Our meta-analysis did not find a significant effect of adjuvant vitamin E over placebo in normalizing serum ALT. Data on the long-term effect of adjuvant vitamin E on histological improvements in NAFLD patients are still lacking. Larger, well-designed randomized controlled trials (RCTs) in children with histological endpoints are still needed to answer this question.
    Saudi Journal of Gastroenterology 05/2014; 20(3). DOI:10.4103/1319-3767.132983 · 1.12 Impact Factor
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