Treatment of NAFLD with diet, physical activity and exercise

Summary
Background

The association between obesity and nonalcoholic fatty liver disease (NAFLD) has not been fully quantified, and the magnitude of NAFLD risk associated with obesity is still unclear. A meta-analysis of cohort studies was performed to elucidate the NAFLD risk associated with obesity.



Methods

Pubmed, Web of Science and Embase were searched for cohort studies assessing NAFLD risk associated with obesity or increased body mass index (BMI). Relative risks (RRs) with 95% confidence intervals (95%CIs) were pooled using random-effects model of meta-analysis.



Results

Twenty-one cohort studies including 13 prospective studies and 8 retrospective studies were finally included. There were a total of 381,655 participants in the meta-analysis. Compared with normal weight, obesity independently led to a 3.5-fold increased risk of developing NAFLD (RR = 3.53, 95%CI 2.48 to 5.03, P < 0.001). Meta-analysis also suggested an obvious dose-dependent relationship between BMI and NAFLD risk (per 1-unit increment in BMI: RR = 1.20, 95%CI 1.14 to 1.26, P < 0.001). Subgroup analyses further identified the robustness of the association above. No obvious risk of publication bias was observed.



Conclusion

Obese individuals have a 3.5-fold increased risk of developing NAFLD, and there is an obvious dose-dependent relationship between BMI and NAFLD risk. © 2016 World Obesity

Obesity is an independent risk factor for non‐alcoholic fatty liver disease: evidence from a meta‐analysis of 21 cohort studies

Non-alcoholic fatty liver disease (NAFLD) has become a major global health burden, leading to increased risk for cirrhosis, hepatocellular carcinoma, type-2 diabetes and cardiovascular disease. Lifestyle intervention aiming at weight reduction is the most established treatment. However, changing the dietary composition even without weight loss can also reduce steatosis and improve metabolic alterations as insulin resistance and lipid profile. The Mediterranean diet (MD) pattern has been proposed as appropriate for this goal, and was recommended as the diet of choice for the treatment of NAFLD by the EASL-EASD-EASO Clinical Practice Guidelines. The MD has an established superiority in long term weight reduction over low fat diet, but it improves metabolic status and steatosis even without it. However, the effect on liver inflammation and fibrosis was tested only in few observational studies with positive results. Furthermore, considering the strong association between NAFLD and diabetes and CVD, the MD has a highly established advantage in prevention of these diseases, demonstrated in randomized clinical trials. The individual components of the MD such as olive oil, fish, nuts, whole grains, fruits, and vegetables, have been shown to beneficially effect or negatively correlate with NAFLD, while consumption of components that characterize a Western dietary pattern as soft drinks, fructose, meat and saturated fatty acids have been shown to have detrimental association with NAFLD. In this review we will cover the epidemiological evidence and the plausible molecular mechanisms by which the MD as a whole and each of its components can be of benefit in NAFLD.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/liv.13435

The Mediterranean dietary pattern as the diet of choice for non-alcoholic fatty liver disease: Evidence and plausible mechanisms.

Obesity is a risk factor for type 2 diabetes mellitus. Among obesity, visceral fat obesity, and ectopic fat obesity, it has been unclear which has the greatest effect on incident diabetes. In this historical cohort study of 8430 men and 7034 women, we investigated the effect of obesity phenotypes on incident diabetes. Obesity, visceral fat obesity, and ectopic fat obesity were defined as body mass index ≥25 kg/m2, waist circumference ≥90 cm in men or ≥80 cm in women, and having fatty liver diagnosed by abdominal ultrasonography, respectively. We divided the participants into eight groups according to the presence or absence of the three obesity phenotypes. During the median 5.8 years follow-up for men and 5.1 years follow-up for women, 286 men and 87 women developed diabetes. Compared to the non-obese group, the hazard ratios (HRs) of incident diabetes in the only-obesity, only-visceral fat obesity, only-ectopic fat obesity groups, and with all-three types of obesity group were 1.85 (95%CI 1.06–3.26, p = 0.05) in men and 1.79 (0.24–13.21, p = 0.60) in women, 3.41 (2.51–4.64, p < 0.001) in men and 2.30 (0.87–6.05, p = 0.12) in women, 4.74 (1.91–11.70, p < 0.001) in men and 13.99 (7.23–27.09, p < 0.001) in women and 10.5 (8.02–13.8, p < 0.001) in men and 30.0 (18.0–50.0, p < 0.001) in women. Moreover, the risk of incident diabetes of the groups with ectopic fat obesity were almost higher than that of the four groups without ectopic fat obesity. Ectopic fat obesity presented the greatest risk of incident type 2 diabetes.

Ectopic fat obesity presents the greatest risk for incident type 2 diabetes: a population-based longitudinal study.

Adipose tissue represents a large volume of biologically active tissue that exerts substantial systemic effects in health and disease. Alcohol consumption can profoundly disturb the normal functions of adipose tissue by inducing adipocyte death and altering secretion of adipokines, pro-inflammatory mediators and free fatty acids from adipose tissue, which have important direct and indirect effects on the pathogenesis of alcoholic liver disease (ALD). Cessation of alcohol intake quickly reverses inflammatory changes in adipose tissue, and pharmacological treatment that normalizes adipose tissue function improves experimental ALD. Obesity exacerbates liver injury induced by chronic or binge alcohol consumption, and obesity and alcohol can synergize to increase risk of ALD and progression. Physicians who care for individuals with ALD should be aware of the effects of adipose tissue dysfunction on liver function, and consider strategies to manage obesity and insulin resistance. This Review examines the effect of alcohol on adiposity and adipose tissue and the relationship between alcohol, adipose tissue and the liver.

Alcohol, adipose tissue and liver disease: mechanistic links and clinical considerations.

Background and Aim
Recent cross-sectional studies have been reported the possibility that light to moderate alcohol consumption might be negatively associated with fatty liver. However, there has been no large-scale longitudinal study addressing an impact of alcohol consumption on a development of fatty liver diagnosed by ultrasonography. Thus, we investigated the impact of alcohol consumption on a natural history of fatty liver.

Methods
We analyzed 5437 apparently healthy Japanese who received the health checkup programs repeatedly over 10 years. In this study, we used a standardized questionnaire for addressing the medical history and lifestyle and used a standardized ultrasonographic diagnosis for fatty liver. The total amount of alcohol consumed per week was calculated and classified into four grades; none or minimal, light, moderate, or heavy alcohol consumption (  280 g/week, respectively). The hazard risks of alcohol consumption for the development of fatty liver were calculated by Cox hazard model after adjusting age, BMI, and parameters for lifestyle.

Results
During 10 years of follow-up, fatty liver was continuously diagnosed just in 10% of men and 20% of women with fatty liver at the baseline. In men, the adjusted hazard risks of light and moderate alcohol consumption for the development of fatty liver were 0.72 (95% confidence interval 0.60–0.86, P < 0.001) and 0.69 (0.57–0.84, P < 0.001), respectively. However, they were not significant in women.

Conclusions
The newly onset of fatty liver was significantly repressed in apparently healthy men who consume light to moderate alcohol.

Modest alcohol consumption reduces the incidence of fatty liver in men: a population-based large-scale cohort study.

Objective The purpose of this study was to determine the relationship between serum γ-glutamyltranspeptidase (GGT) and brachial-ankle pulse wave velocity (baPWV) as an indicator for atherosclerosis in Japanese men and women after adjusting for fatty liver. Design A cross-sectional study. Setting A health check-up centre in Japan. Participants 912 Japanese men and women aged 24–84 years recruited from people who received a medical health check-up programme with a standardised questionnaire and an automatic waveform analyser to measure baPWV. Main outcome measures We measured serum GGT concentrations and baPWV. Fatty liver was diagnosed by standardised criteria using abdominal ultrasonography. The postmenopausal state was defined as beginning 1 year after the cessation of menses. Results In women, log2 GGT was positively associated with baPWV (β=0.11, 95% CI 0.02 to 0.19, p Conclusions The serum GGT level was associated with baPWV, independently of covariates including fatty liver or menopausal state just in women, but not in men.

/pdf/association-between-serum-g-glutamyltranspeptidase-and-4n4h9mprv0.pdf

Yasuhiro Ohshima

Papers

Modest alcohol consumption reduces the incidence of fatty liver in men: a population-based large-scale cohort study.

Association between serum γ-glutamyltranspeptidase and atherosclerosis: a population-based cross-sectional study.