Nutrition Management Strategies for Nonalcoholic Fatty Liver Disease: Treatment and Prevention

Short abstract

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-4-reading-miller a video presentation of this article

Abbreviations

AASLD

American Association for the Study of Liver Diseases

AISF

Italian Association for the Study of the Liver

EASD

European Association for the Study of Diabetes

EASL

The European Association for the Study of the Liver

EASO

European Association for the Study of Obesity

ESPEN

European Society for Clinical Nutrition and Metabolism

FDA

U.S. Food and Drug Administration

MD

Mediterranean diet

N/A

not available

NAFL

nonalcoholic fatty liver

NAFLD

nonalcoholic fatty liver disease

NASH

nonalcoholic steatohepatitis

Background

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease around the world, estimated to affect 25% of the US population and 15% to 35% of the global population.1 NAFLD is the hepatic manifestation of metabolic syndrome in individuals who do not consume large quantities of alcohol.2, 3 NAFLD diagnoses are rising globally, appearing to follow the rising rates of obesity. Patients with NAFLD are commonly obese and/or have diabetes or other comorbidities (hypertension, hyperlipidemia, insulin resistance, etc.).4 Patients with NAFLD are also at higher risk for development of cardiovascular disease, beyond standalone risk factors for heart disease. ⁵

The hallmark feature of NAFLD is excess hepatic fat, defined as >5% of total liver weight.6 NAFLD includes two distinct conditions: nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH).7 The latter includes a range of disease progression, including fibrosis, cirrhosis, and hepatocellular carcinoma.7 The existence of hepatic fat deposits alone (simple NAFL) is relatively benign.8 However, 50% of patients with NAFLD will experience complications.8 Current management is rooted in lifestyle changes, that is, diet modification, exercise, and ultimately weight loss, with combination interventions being most effective.8

Pathogenesis

The pathogenesis of NAFLD is not clear; however, obesity and insulin resistance are believed to influence development.3 Epidemiological studies suggest a correlation between unhealthy lifestyles and the development and progression of NAFLD.7 As previously stated, NAFLD risk correlates with obesity.7

Weight gain is commonly the result of energy imbalance from increased caloric intake (food) and reduced caloric expenditure (activity level, sedentary behavior). A diet high in calories, excess saturated fat, refined carbohydrates, sugar‐sweetened beverages, high fructose intake, and the “Western diet” influence this imbalance.2

Treatment

Pharmacotherapy

Currently, there are no US Food and Drug Administration (FDA)‐approved pharmacotherapy treatments for NAFLD or the existence of steatosis itself.3, 7 Current treatment is centered on lifestyle modification to achieve weight loss.7 Approved weight loss medications may be warranted, with consideration for other comorbidities such as cardiovascular health.6 There are currently five FDA‐approved medications: orlistat (prescription: Xenical; over the counter: Alli), lorcaserin (Belviq), phentermine‐topiramate (Qsymia), naltrexone‐bupropion (Contrave), and liraglutide (Saxenda).10 Appropriateness of weight loss medications is left to a physician’s assessment. Bariatric surgery may also be an option to treat underlying obesity in patients with NAFLD, when lifestyle measures prove unsuccessful or inadequate, or benefits of surgery outweigh risks.3, 6

Lifestyle Modification

Lifestyle modification that leads to weight loss is the current standard for NAFLD treatment. Weight loss generally reduces hepatic steatosis, regardless of how it is achieved.5 A 5% weight loss has been shown to reduce steatosis, a loss of 7% (or more) improves NASH histology, and 10% or greater weight loss can affect fibrosis regression (Table 1).5 Weight loss can be achieved more successfully with a combination of moderate dietary restriction paired with physical activity.8

Table 1.

Weight Loss Percentages and Impact on NAFLD

Weight Loss Achieved	Steatosis	NASH	Fibrosis Regression
5%	↓	No impact	No impact
7%	↓	↓	No impact
>10%	↓ (universal resolution)	↓	↓ (improvement by at least one stage)

Table 2 summarizes the NAFLD treatment recommendations/guidelines of The European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and the European Association for the Study of Obesity (EASO), in addition to the American Association for the Study of Liver Diseases (AASLD), European Society for Clinical Nutrition and Metabolism (ESPEN), and Italian Association for the Study of the Liver (AISF). Collectively, these groups all advocate for lifestyle modification that involves a hypocaloric diet, engagement in physical activity, limited sugar intake, and achievement of 7% weight loss.5, 6, 7, 9

Table 2.

Summary of Guidelines for NAFLD Management

	Source
	EASL/EASD/EASO Clinical Practice Guidelines for the Management of NAFLD7	AASLD Practice Guidance: The Diagnosis and Management of NAFLD6	ESPEN Guideline on Clinical Nutrition in Liver Disease5	AISF Position Paper on NAFLD: Updates and Future Directions9
Overall message	Diet and lifestyle change	Lifestyle change	Lifestyle change (weight loss, increased physical activity)	Lifestyle change (weight loss, physical activity, and healthy diet)
Energy restriction	500‐1000 kcal/day (to target 500‐1000 g weight loss per week)	Hypocaloric diet (reduction of 500‐1000 kcal/day)	Hypocaloric diet (according to current obesity guidelines)	Low‐calorie diet (1200‐1600 kcal/day)
Weight loss target	7%‐10%	3%‐5% (to improve steatosis)	7%‐10% (in obese patients)	7%‐10%
		7%‐10% (for histology improvement)	>10% (to improve fibrosis)
Macronutrient composition	Low to moderate fat and moderate to high carbohydrate	N/A	“Irrespective of macronutrient composition”	Low fat, low carbohydrates
	Low‐carbohydrate, ketogenic diets or high protein		Mediterranean diet to improve steatosis and insulin sensitivity	<30% fat (<10% saturated fat)
				~50% carbohydrate
				Gold standard—fiber‐rich, low‐carbohydrate (incorporate complex carbohydrate), low‐fat, Mediterranean pattern
Fructose intake	Avoid fructose‐containing beverages and foods	N/A	N/A	Reduce high‐sugar food
				Avoid fructose
Alcohol intake	Below risk threshold (<30 g for men and <20 g for women)	Should not consume heavy amounts	Abstain (to reduce risk for comorbidity and improve liver biochemistry and histology)	N/A
Coffee consumption	No liver‐related limitations	N/A	“More likely to benefit health than harm”	Moderate use
Exercise/physical activity	150‐200 min/week of moderate‐intensity aerobic physical activities in 3‐5 sessions	Moderate‐intensity exercise	Advised to exercise (benefits without achieving weight loss)	150‐200 min/week of moderate intensity; ~4 sessions/week
	Resistance training is effective and promotes musculoskeletal fitness	Exercise alone may prevent or improve hepatic steatosis	Increased physical activity (to improve insulin resistance in normal‐weight patients with NAFLD/NASH)	Aerobic and resistance are effective
Maintenance phase	Long‐term maintenance of weight loss combined with physical activity	N/A	N/A	N/A

Diet

The primary diet goal is to implement a hypocaloric diet to create a caloric deficit. A deficit of at least 500 calories/day is commonly advised for weight loss. 2, 6, 7, 10 Caloric restriction supports weight loss and subsequently promotes fat mobilization from the liver. Current evidence does not provide a consensus on the ideal macronutrient composition of the diet. The best diet is the one a patient can follow, based on individual preferences and eating behaviors.10 Low‐carbohydrate/higher‐protein diets have been associated with metabolic benefits, independent of weight loss.2 Overall, more studies are needed in the area of macronutrient composition.

The Mediterranean diet (MD) is the most recommended diet pattern for NAFLD management.4, 7 It has shown the ability to improve liver steatosis in several studies, independent of caloric restriction.2, 4, 6, 11 The MD is traditionally plant based (whole grains, legumes, fruit, vegetables), lower in carbohydrates (limited simple sugars and refined carbohydrates), and rich in monounsaturated (mostly olive oil) and omega‐3 fats, and incorporates limited red meat and limited low‐fat dairy.2, 6, 10, 11

One crossover study compared the MD with a low‐fat/high‐carbohydrate diet, modeled after the current diet standard for patients with cardiovascular risk (i.e., the American Heart Association dietary recommendations).11 Overall, subjects experienced a greater reduction in liver fat content and insulin sensitivity (independent of weight loss) after following the MD versus a low‐fat/high‐carbohydrate comparison diet, as summarized in Table 3.11 The MD is well regarded in the medical community and has clearly documented health benefits for reduction of cardiovascular risk.

Table 3.

MD Versus Comparison Diet

Characteristics	MD	Comparison Diet
Description	High fat, low carbohydrate, isocaloric	Low fat, high carbohydrate, isocaloric
Diet abbreviation	MD	LF/HCD
Diet model	MD (established benefit to reduce cardiovascular risk)	Australian National Heart Foundation and American Heart Association
Primary fat type and source	Monounsaturated (olive oil) and omega‐3 polyunsaturated (marine sources)	Omega‐6 polyunsaturated (low in saturated fat)
Calories from carbohydrate	40%	50%
Calories from fat	40%	30%
Calories from protein	20%	20%
Study overview	Randomized crossover intervention study n = 12 Step 1: patients randomized to either MD or LF/HCD for 6 weeks Step 2: 6‐week washout period Step 3: 6 weeks on alternative study diet (MD or LF/HCD)
Impact on insulin resistance	Improved insulin resistance	No change
Impact on liver fat	Statistically significant ↓	Small ↓
Cardiovascular disease risk factors	Significant ↓ in systolic blood pressure	Small ↓ in systolic blood pressure
Impact on weight	No change	No change

Adapted with permission from Journal of Hepatology.11 Copyright 2013, European Association for the Study of the Liver.

Added Sugars

Evidence suggests that there is a correlation between refined sugar intake (as fructose) and NAFLD. ⁴ Fructose (predominantly from table sugar and corn syrup) is consumed in excess in the Western diet.2 For the average American diet, fructose makes up 10% of caloric intake.2 The association is strongest with sugar‐sweetened beverages, because fructose‐rich diets increase hepatic synthesis of triglycerides.2, 4 Sugar‐sweetened beverages are a common source of empty calories from fructose.4 Reducing intake can be a practical tool in reducing extraneous calories and supporting a calorie deficit for weight loss.

Vitamin E

Vitamin E is a fat‐soluble vitamin that functions as an antioxidant. The Pioglitazone versus Vitamin E versus Placebo for the Treatment of Non‐Diabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial showed supplementation of 800 IU vitamin E (α‐tocopherol) per day (in individuals without diabetes) improved steatosis and inflammation, and induced NASH resolution.2, 7 Long‐term safety (mortality risk) is of concern. Vitamin E supplementation is advised only for nondiabetic patients with NAFLD with histologically confirmed NASH, per the PIVENS trial study demographics.2, 5

Physical Activity

Engagement in physical activity is supported in the NAFLD management guidelines for EASL/EASD/EASO, AASLD, ESPEN, and AISF.5, 6, 7, 9 A meta‐analysis of randomized trials provides strong evidence that physical activity is associated with a significant reduction in liver fat content.1 A significant reduction in blood levels of aminotransferases was also observed.1 This suggests that physical activity should be recommended in combination with diet changes, or independently for NAFLD management.1 Data to support a specific quantity of activity are lacking; however, advising patients to achieve the 2008 Physical Activity Guidelines for Americans (150 minutes per week of moderate intensity) is a practical benchmark.10

Treatment Summary

The established treatment for NAFLD is lifestyle modification, with the goal of weight reduction. A targeted weight loss of 7% to 10% is advised; however, benefits are observed with a minimum weight loss of 5%. A hypocaloric diet, individualized to the patient’s dietary preferences, should be encouraged to achieve weight loss. Refined sugar in the form of fructose (such as sugar‐sweetened beverages) should be discouraged. The best diet will be the hypocaloric one a patient can stick with long term to sustain weight loss. ⁵ , ¹⁰ Physical activity should be encouraged, because combination interventions (diet and physical activity) are most effective at improving NAFLD.8 Nutrition counseling of overweight and obese patients with NAFLD should be performed while following current guidelines for dietary management of obesity.5 Weight loss success can be maximized through involvement of a multidisciplinary team (registered dietitians, physicians, exercise therapists) and behavioral therapy.4, 10

Prevention

NAFLD is correlated with obesity and insulin resistance.3 To help prevent NAFLD development, patients should be encouraged to engage in healthy lifestyle behaviors. Health care professionals are encouraged to support patients in maintaining a healthy weight. If a patient is overweight or obese, encourage the patient to lose weight to reduce NAFLD development risk. If a patient is displaying signs of insulin resistance, urge the patient to undertake action to improve glycemic control via diet modifications, increasing activity level, or medical management as appropriate. Support a healthy, well‐balanced diet, possibly rooted in the MD principles.11 Advise limited intake of refined sugars, especially fructose, with attention to sugar‐sweetened beverages. Overall, a healthy lifestyle is key to both treatment and prevention.