Exercise-based Interventions for Nonalcoholic Fatty Liver Disease: A Meta-analysis and Meta-regression

Orci, Lorenzo A.; Gariani, Karim; Oldani, Graziano; Delaune, Vaihere; Morel, Philippe; Toso, Christian

doi:10.1016/j.cgh.2016.04.036

Cited by 186 publications

(163 citation statements)

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“…A significant consumption of fructose leads to hepatic lipid accumulation and steatosis, steatosis being considered pathological when an abnormal accumulation of lipid droplets is observed in the cytoplasm of at least 5% of hepatocytes [4]. At this point, hepatic steatosis (HS) may be reversed through nutritional and physical exercise approaches [10,11]. Adversely, chronic consumption of fructose promotes several processes such as inflammation and cellular stress, which is responsible for the irreversibility of hepatic disorders and the progression of the disease [4].…”

Section: Introductionmentioning

confidence: 99%

Fructose and NAFLD: The Multifaceted Aspects of Fructose Metabolism

2017

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Among various factors, such as an unhealthy diet or a sedentarity lifestyle, excessive fructose consumption is known to favor nonalcoholic fatty liver disease (NAFLD), as fructose is both a substrate and an inducer of hepatic de novo lipogenesis. The present review presents some well-established mechanisms and new clues to better understand the pathophysiology of fructose-induced NAFLD. Beyond its lipogenic effect, fructose intake is also at the onset of hepatic inflammation and cellular stress, such as oxidative and endoplasmic stress, that are key factors contributing to the progression of simple steatosis to nonalcoholic steatohepatitis (NASH). Beyond its hepatic effects, this carbohydrate may exert direct and indirect effects at the peripheral level. Excessive fructose consumption is associated, for example, with the release by the liver of several key mediators leading to alterations in the communication between the liver and the gut, muscles, and adipose tissue and to disease aggravation. These multifaceted aspects of fructose properties are in part specific to fructose, but are also shared in part with sucrose and glucose present in energy–dense beverages and foods. All these aspects must be taken into account in the development of new therapeutic strategies and thereby to better prevent NAFLD.

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Section: Introductionmentioning

confidence: 99%

Fructose and NAFLD: The Multifaceted Aspects of Fructose Metabolism

2017

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“…While there is general consensus that many types of lifestyle interventions should be effective in reducing steatosis and improving histological markers of disease progression, comparison proves difficult because of the diversity of intervention protocols and NAFLD diagnostic and outcome criteria used in trials 10. Recent meta-analyses examining exercise interventions suggest positive effects on reduction in alanine aminotransferase (ALT) levels and intrahepatic fat, although the clinical significance of reported standard mean differences can be difficult to interpret 11 12. These reviews highlight the considerable heterogeneity in duration and types of exercise intervention employed.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review

Kenneally

Sier

Moore

2017

BMJ Open Gastroenterol

109

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BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, with prevalence above 30% in many adult populations. Strongly associated with obesity, weight loss through diet and physical activity is the mainstay of its management. Weight loss can be difficult to achieve and maintain however, and uncertainty exists as to which lifestyle changes are most effective.ObjectiveThe aim of this work was to systematically evaluate randomised controlled trials assessing diet, exercise or combination interventions aimed at reducing steatosis or markers of NAFLD activity.DesignMedline, Scopus and Cochrane databases were searched from 1 January 1980 through to 31 July 2016, for intervention trials assessing the effects of diet, weight loss, exercise or any combination thereof, on NAFLD disease markers in human adults. Risk of publication bias and study quality was assessed using the American Dietetic Association Quality Criteria Checklist.ResultsFrom a total of 1710 identified records, 24 articles met the inclusion and exclusion criteria; 6 assessed weight loss using dietary restriction, 10 assessed exercise and 8 were combination interventions. While all of the trials demonstrated significant reduction in steatosis and/or markers of NAFLD activity, combination interventions appear to be the most effective at improving NAFLD. Results suggest that 5–10% weight loss using a modestly hypocaloric diet of 500 kcal less per day than calculated energy requirement, in combination with 30–60 min exercise on 3–5 days per week should be recommended.ConclusionsWe conclude this amount of weight loss is achievable in the trial setting but is challenging in the clinical environment. High-intensity, multidisciplinary intervention in specialist clinics is likely to be required in order to manage NAFLD by lifestyle modification alone. This systematic review protocol was registered prospectively at PROSPERO as CRD42016032764.

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“…Lifestyle interventions, consisting of a weight decreasing diet and increases in physical exercise, remain the cornerstone of treatment of pediatric NAFLD, even if several studies indicate improvement only in metabolic parameters and liver steatosis [8,9]. Consequently, in the last decade, several pharmacological approaches have been tested that are focused on ameliorating mechanisms of liver damage.…”

Section: Introductionmentioning

confidence: 99%

Docosahexanoic Acid Plus Vitamin D Treatment Improves Features of NAFLD in Children with Serum Vitamin D Deficiency: Results from a Single Centre Trial

et al. 2016

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BackgroundThere are no licensed treatments for non alcoholic fatty liver disease (NAFLD) in adults or children. In NAFLD, several studies have shown a benefit of omega-3 fatty acid treatment on lipid profile, insulin-sensitivity and hepatic steatosis and it has also been suggested that Vitamin D treatment has potential antifibrotic properties in liver disease.Trial DesignTo date, however, there are no studies that have tested the combination of Docosahexanoic acid (DHA) and vitamin D treatment which may benefit the whole spectrum of disease in NAFLD. Our aim therefore, was to test the effect of daily DHA (500 mg) plus vitamin D (800 IU) treatment, in obese children with biopsy-proven NAFLD and vitamin D deficiency, in a randomized, double-blind placebo-controlled trial.MethodsThe 41/43 patients completed the study (18-treatment, 23-placebo). At 12 months: i) the main outcome was liver histology improvement, defined by NAS; ii) the secondary outcome was amelioration of metabolic parameters.ResultsDHA plus vitamin D treatment reduced the NAFLD Activity Score (NAS), in the treatment group (5.4 v1.92; p<0.001 for baseline versus end of study). There was no change in fibrosis score, but a reduction of the activation of hepatic stellate cells (HSC) and fibrillar collagen content was noted (3.51±1.66 v. 1.59±1.37; p = 0.003) in treatment group. Moreover, the triglycerides (174.5 vs. 102.15 mg/dl), ALT (40.25 vs. 24.5 UI/l) and HOMA-IR (4.59 vs. 3.42) were all decreased with treatment.ConclusionDHA plus vitamin D treatment improved insulin-resistance, lipid profile, ALT and NAS. There was also decreased HSC activation and collagen content with treatment.

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Exercise-based Interventions for Nonalcoholic Fatty Liver Disease: A Meta-analysis and Meta-regression

Abstract: In a meta-analysis of randomized trials, we found strong evidence that physical activity reduces intrahepatic lipid content and markers of hepatocellular injury in patients with NAFLD. This effect correlated with baseline body mass index.

Cited by 186 publications

References 59 publications

Fructose and NAFLD: The Multifaceted Aspects of Fructose Metabolism

Fructose and NAFLD: The Multifaceted Aspects of Fructose Metabolism

Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review

Docosahexanoic Acid Plus Vitamin D Treatment Improves Features of NAFLD in Children with Serum Vitamin D Deficiency: Results from a Single Centre Trial

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