Currently there are no approved pharmaceutical agents specifically for Non-Alcoholic Fatty Liver Disease (NAFLD), and lifestyle and dietary interventions aimed at weight loss remains the mainstay of clinical management guidelines.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Referred to as the hepatic component of metabolic syndrome, NAFLD ranges from simple steatosis to complications such as steatohepatitis, fibrosis, cirrhosis and end-stage liver failure, or hepatocellular carcinoma.

Evidence suggests that it is possible to halt and in some instances reverse disease progression in the earlier stages of NAFLD. Many therapeutic agents and nutritional supplements have been studied for the same; however only a few have successfully reached phase III clinical trials. Since there are no pharmaceutical agents for NAFLD, lifestyle and diet changes stand at the forefront of treatment.

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The main goals of lifestyle-based treatment include:

• Caloric restriction
• Changes in diet composition
• Increased exercise
• Stress reduction
• Improved sleep

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Recommendations that may aid better management of Non-Alcoholic Fatty Liver Disease

Recommendation 1: Weight reduction achieved through lifestyle intervention leads to improvements in liver histology in NASH

A randomised controlled trial published in the Hepatology (Baltimore, Md.) concluded that the participants who achieved study weight loss goal (≥7%) had significant improvements in steatosis (−1.36 vs −0.41, p<0.001), lobular inflammation (−0.82 vs −0.24, p=0.03), ballooning injury (−1.27 vs −0.53, p=0.03) and NAS (−3.45 vs −1.18, p<0.001).

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Recommendation 2: Hepatic triglyceride reductions in NAFLD are significantly greater with dietary carbohydrate restriction than with calorie restriction

An interventional study published in the American Journal of Clinical Nutrition (2011) studied the effectiveness of 2 weeks of dietary carbohydrate and calorie restriction at reducing hepatic triglycerides in patients with NAFLD. Even though the Mean (±SD) weight loss was similar between the calorie-restricted group and the carbohydrate-restricted group; liver triglycerides decreased significantly more (P = 0.008) in the carbohydrate-restricted subjects (-55 ± 14%) than in calorie-restricted subjects (-28 ± 23%). The authors correlated this finding to enhanced lipid disposal via hepatic and whole-body oxidation in the carbohydrate-restricted group.

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Recommendation 3: A low-calorie, low-carbohydrate soy-containing diet could have beneficial effects on liver enzymes, malondialdehyde, and serum fibrinogen levels in patients with NAFLD

A trial which studied the effect of three kinds of diets (8 weeks) on patients with NAFLD was published in the journal Nutrition (2014). In the randomised parallel study, patients were randomly assigned to consume a low-calorie diet; a low-calorie, low-carbohydrate diet; or a low-calorie, low-carbohydrate soy-containing diet. The study found that the low-calorie, low-carbohydrate soy-containing diet reduced alanine aminotransferase (-15.2 ± 12.1 versus -6.8 ± 4.6 in the low-calorie, low-carbohydrate diet, and -6.4 ± 4.4 IU/L in the low-calorie diet; P = 0.02) and serum fibrinogen levels (-49.1 ± 60.1 versus -12.9 ± 8.1 and -17.4 ± 8.4 g/L, respectively; P = 0.01). The soy-containing diet also reduced malondialdehyde and aspartate aminotransferase more than the other diets.

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Recommendation 4: Mediterranean diet (MD) may be a beneficial nutritional approach in NAFLD patients

Vegetables, fruits, nuts, whole grains, and vegetable oils form the base of a MD. Weekly two servings of fish are recommended. Moderate servings of poultry and dairy are also suggested.

A multiple logistic regression analysis, by Baratta et al. in the American Journal of Gastroenterology (2017) concluded that MD adherence (intermediate vs. low OR = 0.115; P = 0.041; high vs. low OR: 0.093; P = 0.030) were independently associated with NAFLD. NAFLD prevalence significantly decreased from subjects with low to high adherence to MD (from 96.5% to 71.4%, P < 0.001).

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Recommendation 5: In NAFLD patients, consumption of the Dietary Approaches to Stop Hypertension (DASH) diet confers beneficial effects on weight, body mass index, ALT, ALP and triglycerides

The DASH diet comprises of fruits, vegetables, whole grains, and low‐fat dairy products. A randomised controlled clinical trial published in the journal Liver International found that the DASH diet resulted in significant reductions in serum triglycerides (P = 0.04) and total‐/HDL‐cholesterol ratio (P = 0.01). A decreased concentrations of serum high‐sensitivity C‐reactive protein (hs‐CRP) (P = 0.03), malondialdehyde (MDA) (P = 0.04), increased levels of nitric oxide (NO) (P = 0.01) and glutathione (GSH) (P = 0.009) were also observed in the DASH group.

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Recommendation 6: Physical activity reduces intrahepatic lipid content and markers of hepatocellular injury in patients with NAFLD

As per a meta-analysis, published in the journal Clinical Gastroenterology and Hepatology (2016), physical activity was associated with a significant reduction in intrahepatic lipid content (standardised mean difference, -0.69; 95% confidence interval [CI], -0.90 to -0.48), reductions in alanine aminotransferase (weighted mean difference, -3.30 IU/L; 95% CI, 5.57 to -1.04) and aspartate aminotransferase (weighted mean difference, -4.85 IU/L; 95% CI, -8.68 to -1.02). By meta-regression, the authors found that the patients with increasingly high BMI at enrolment demonstrated an increasingly intense decline in liver fat content.

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Recommendation 7: Resistance training (RT) may serve as a complement to treatment of NAFLD

As per a randomised clinical trial published in 2014 in the World Journal of Gastroenterology, hepatorenal-ultrasound index (HRI) scores were reduced significantly in the RT arm as compared to the stretching arm (-0.25 ± 0.37 vs -0.05 ± 0.28, P = 0.017). The RT arm had a significantly higher reduction in total, trunk and android fat with increase in lean body mass. The RT arm also presented with a significant reduction in serum ferritin and total cholesterol.

Another study by Takahashi A, et al. published in the International journal of sports medicine (2015), revealed that resistance exercise comprising squats and push-ups can help to improve the characteristics of metabolic syndrome in patients with non-alcoholic fatty liver disease. The study demonstrated that resistance exercises significantly increased the fat-free mass and muscle mass. On the other hand hepatic steatosis grade, mean insulin and ferritin levels, and the homeostasis model assessment-estimated insulin resistance index were significantly decreased in the exercise group.

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Recommendation 8: Resistance training and aerobic training are equally effective in reducing hepatic fat content among type 2 diabetic patients with NAFLD

As per the RAED2 randomised trial published in the journal Hepatology, hepatic fat content was markedly reduced (P < 0.001) in the aerobic (AER) and the resistance (RES) training groups (mean relative reduction from baseline [95% confidence interval] -32.8% [-58.20 to -7.52] versus -25.9% [-50.92 to -0.94], respectively). Hepatic steatosis disappeared in about one-quarter of the patients in each intervention group (23.1% in the AER group and 23.5% in the RES group).

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Recommendation 9: Diet plus exercise is more efficacious than exercise alone in the lifestyle modification treatment of NAFLD

A prospective, case-controlled study which studied the effects of varied therapeutic lifestyle programs on NAFLD patients was published in the Journal of the Chinese Medical Association (2008). A total of 54 subjects were subdivided into 3 groups: Diet plus exercise group (DPE), Exercise group (E group) and Control group (C group). The DPE group demonstrated significant improvements in the serum level of total cholesterol, insulin sensitivity, liver biochemistry, severity of fatty liver, physical fitness and diastolic blood pressure. The 10-week diet-plus-exercise and exercise-only therapeutic lifestyle programs were both effective in improving anthropometric indices, insulin sensitivity, ultrasound findings and physical fitness in ultrasound-diagnosed NAFLD patients, however the improvement range from the diet-plus-exercise program was more obvious than that of the exercise only program. Additionally, the diet-plus-exercise program offered significant improvement in liver biochemistry which the exercise-only program did not.

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Recommendation 10: Lifestyle counselling interventions targeting improvement in physical activity, nutritional behaviours and weight loss are a practical and effective method for improving the health of patients with elevated liver enzymes and a range of metabolic risk factors

A 2009 study in the Journal of Gastroenterology and Hepatology evaluated the effects of lifestyle counselling on improving the health of patients with elevated liver enzymes and a range of metabolic risk factors.

The interventional study randomised patients to receive either a moderate- (6 sessions/10 weeks) or low-intensity (3 sessions/4 weeks) lifestyle counselling intervention or control group. The moderate-intensity group reported an improvement in all metabolic risk factors. Reduction in liver enzymes was greatest in the moderate-intensity intervention group and least in the control group. The likelihood of elevated alanine aminotransferase (ALT) levels in both the moderate and low-intensity groups was reduced by over 70% compared to controls. The proportion of subjects achieving weight loss (>or= 2%) was significantly higher in the moderate-intensity intervention group (66%) versus the low-intensity intervention group (39%; P < 0.05) and controls (29%; P < 0.001).

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Recommendation 11: There is a significantly increased risk of NAFLD among individuals who had short sleep duration

As per a meta-analysis published in 2016 in the Journal of Gastroenterology and Hepatology, the risk of NAFLD in participants who had short sleep duration was significantly higher than participants with longer sleep duration with pooled risk ratios of 1.19 (95% confidence interval, 1.04-1.36, I2 = 0%).

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Conclusion

Lifestyle and dietary interventions are crucial for the treatment of NAFLD and they are highly recommended by health authorities such as the European Association for the Study of the Liver (EASL) on NAFLD/NASH and American Association for the Study of Liver Diseases (AASLD). Strategies should focus on maintenance programs with special emphasis to achieve a sustained response, rather than a short-term, transient benefit. An individualised assessment may be beneficial in determining the proper lifestyle adaptation for each patient.