The American Gastroenterological Association (AGA) has issued a clinical practice update regarding lifestyle modification interventions for treating patients with nonalcoholic fatty liver disease (NAFLD), as published in Gastroenterology.1

The AGA provided 10 Best Practice Advice statements that address key issues in the clinical management of patients with NAFLD. “Lifestyle modification including significant weight loss through hypocaloric diet and exercise is considered as a first-line intervention for the treatment of NAFLD as weight loss is associated with a reduction in liver fat, which provides a potential for reversal of disease progression,” stated the AGA authors. “These guidance statements require a team approach to improve adherence such that the use of personnel educated in diet and in exercise should be incorporated so that each patient’s diet and exercise plan can be individualized to be culturally sensitive, socially appropriate, obtainable, and measurable.”

Lifestyle modification focused on diet and physical activity to achieve weight loss and avoiding alcohol is the foundation of treatment for all patients with NAFLD, according to the AGA. “The reduction of body weight results in decreased liver fat and improved glucose control/insulin sensitivity reducing the risks for diabetes mellitus [and] cardiovascular disease (CVD), as well as decreasing the risks of progressive liver disease,” noted the AGA.


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Research has shown that weight loss can improve multiple aspects of NAFLD histology. “A goal of 10% total body weight loss should be considered for patients with overweight or obese NAFLD,” the AGA recommended. Several systematic reviews and meta-analyses have found that the more intensive the weight loss intervention, the more weight loss that occurs, which can lead to improved NAFLD-related liver biomarkers.

A hypocaloric diet is an important component of the treatment plan for patients with NAFLD, according to the AGA. Patients should decrease daily caloric intake by 500 to 1000 kcal/d or to a target of 1200 kcal/d for women and 1400 to 1500 kcal/d for men. This caloric restriction has been associated with weight loss, improvement in insulin resistance, and decrease in liver enzymes and intrahepatic fat.

The Mediterranean diet has been the most frequently studied diet for patients with NAFLD and nonalcoholic steatohepatitis (NASH). The Mediterranean diet focuses on the daily consumption of fresh vegetables, fruit, legumes, minimally processed whole grains, and fish, as well as omega-3 fatty acids such as olive oil, nuts, and seeds as the primary fat sources, with minimal to low consumption of dairy and red and processed meat.

“The Mediterranean diet is beneficial in the prevention and treatment of multiple metabolic conditions including cardiovascular disease and diabetes mellitus and is associated with a decrease in overall mortality,” stated the AGA.

Foods that have a high level of saturated fatty acids such as meat are associated with CVD and diabetes mellitus. “While the impact of eliminating meat from the diet on NAFLD has not yet been evaluated, limiting the overall meat intake and avoidance of the processed meats in patients with NAFLD should be considered,” noted the AGA.

The consumption of fructose, such as that found in sugar-sweetened beverages, is associated with higher fibrosis stages in adults with NAFLD. In older adults, fructose consumption is associated with increased hepatic inflammation and hepatocellular ballooning. “However, fructose contained in fruits is not associated with NAFLD, so fruit consumption should not be restricted,” advised the AGA.

Limited research has suggested that patients with normal weight NAFLD can significantly benefit from intensive lifestyle intervention and weight loss through improvement in hepatic fat, decreased waist circumference, and decreased low-density lipoprotein levels. “A reduction of body weight and remission of NAFLD is dose dependent for those with normal weight NAFLD,” noted the AGA.

Studies of meal replacement diets for treating patients with NAFLD have been limited by their small size and have failed to demonstrate a benefit; therefore, further studies are needed before intermittent fasting can be routinely considered for patients with NAFLD.

“A high-protein, low-carbohydrate diet cannot yet be considered as the preferred diet for the treatment of NAFLD,” the AGA commented. “Patients should be counseled to follow a Mediterranean diet … and modulate the carbohydrate and protein content that best suits them.”

The effect of exercise on NAFLD can enhance the positive effects of a hypocaloric diet. “Physical activity, independent of weight loss, can improve NAFLD by reducing hepatic fat content, in part by improving the body’s peripheral sensitivity to insulin, decreasing hepatic de novo lipogenesis, decreasing adipocyte lipolysis, and reducing free fatty acid delivery to the liver,” stated the AGA.

Beneficial physical activity includes aerobic activity such as walking or stationary biking, and resistance training can be accomplished with load-lifting exercises such as weight training with a weight machine. Studies have varied regarding aerobic exercise type and duration. “In general 150 to 300 minutes of moderate intensity exercise (3-6 metabolic equivalents [METS]) or 75 to 150 minutes of vigorous-intensity exercise (>6 METS) should be considered for patients,” according to the AGA.

“It is important to note that exercise seems to enhance the weight reduction benefit of diet, so moderate physical activity in conjunction with the Mediterranean diet may be associated with the most weight loss as well as reduction in visceral adipose tissue and percent intrahepatic fat,” the AGA commented.

The presence of coexisting metabolic conditions among patients with NAFLD and NASH is high and includes obesity, diabetes, hyperlipidemia, hypertriglyceridemia, hypertension, and metabolic syndrome. “Since these co-morbidities are also associated with the development of CVD, CVD remains 1 of the major causes of death among those with NAFLD and or NASH, and as such, patients with NAFLD and NASH with these co-morbidities should be referred for further evaluation of cardiovascular health.”

Data are conflicting regarding the role of alcohol consumption in the development and progression of NAFLD. Studies have suggested that low to moderate alcohol use is associated with decreased odds of NASH, hepatocyte ballooning, and fibrosis in NAFLD, although they have been limited by their cross-sectional nature and inability to establish causality. In a recent large prospective study, Åberg et al found that alcohol use, even at low levels, is associated with increased liver-related outcomes in patients with NAFLD.2

“Adults with NAFLD should restrict alcohol consumption to reduce liver-related events, and smokers (current or prior) should avoid alcohol entirely,” advised the AGA.

Sarcopenia is common among patients with NASH cirrhosis, and sarcopenic obesity (low muscle mass in the presence of obesity) in cirrhosis is associated with poor clinical outcomes, including increased mortality.

“To avoid caloric deficits, an individualized dietary plan should be devised to meet required caloric and nutritional requirements,” recommended the AGA. “In this context, the minimum protein intake [of] 1.2 to 1.5 g/kg with branched chain amino acids obtained from protein sources such as chicken, fish, eggs, nuts, lentils, and/or soy should be considered. Patients should be encouraged to eat frequent small meals and avoid more than 4 to 6 hours between meals.”

The study authors advise that a bedtime snack that contains protein and at least 50 g of complex carbohydrates should also be considered. “Given the complexity of the nutritional needs of this group, consultation with a specialized nutritionist is preferred,” the AGA committee commented. “In additional to dietary changes, moderate intensity exercise may be beneficial, ideally for a duration of 150 minutes per week.”

This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology.

The AGA’s Best Practice Advice (BPA) Statements

BPA 1Lifestyle modification using diet and exercise to achieve weight loss is beneficial for all patients with nonalcoholic fatty liver disease (NAFLD).  
BPA 2Among patients with nonalcoholic steatohepatitis (NASH), weight loss of ≥5% of total body weight can decrease hepatic steatosis, weight loss of ≥7% can lead to NASH resolution, and weight loss of ≥10% can result in fibrosis regression or stability.  
BPA 3Clinically significant weight loss generally requires a hypocaloric diet targeting 1200 to 1500 kcal/d or a reduction of 500 to 1000 kcal/d from baseline.
BPA 4Adults with NAFLD should follow the Mediterranean diet, minimize intake of saturated fatty acids (specifically red and processed meat), as well as limit or eliminate consumption of commercially produced fructose.
BPA 5A hypocaloric diet should be implemented for patients with lean NAFLD (BMI 26 kg/m2 for non-Asian individuals or BMI 24 kg/m2 for Asian individuals) with a lower target weight loss threshold of 3% to 5% as they experience similar histologic benefits for steatosis and NASH as patients with overweight or obese NAFLD.  
BPA 6The effect of other specific hypocaloric diets such as low carbohydrate/high protein diets, meal replacement protocols, intermittent fasting, and vitamin supplementation on histologic NAFLD end points has been inadequately studied to support routine use in NAFLD-specific treatment.
BPA 7Regular physical activity should be considered for patients with NAFLD with a target of 150 to 300 minutes of moderate intensity or 75 to 150 minutes of vigorous-intensity aerobic exercise per week. Resistance training exercise may be complementary to aerobic exercise and may have independent effects on NAFLD. The impact of exercise on NAFLD can enhance the positive effect of a hypocaloric diet.
BPA 8Patients with NAFLD should be evaluated for coexisting metabolic conditions such as obesity, diabetes mellitus, hypertension, dyslipidemia, and CVD. These comorbidities should be aggressively managed.
BPA 9Alcohol consumption should be restricted or eliminated from the diets of adults with NAFLD.
BPA 10Sarcopenia is commonly observed in patients with NASH cirrhosis. This group may require specialized dietary and activity management.

Disclosures: Some of the authors reported affiliations with pharmaceutical and biotechnology companies. Please see the original reference for a full list of disclosures.

References

1. Younossi ZM, Corey KE, Lim JK. AGA clinical practice update on lifestyle modification using diet and exercise to achieve weight loss in the management of nonalcoholic fatty liver disease (NAFLD): expert review. Gastroenterology. Published online December 8, 2020. doi:10.1053/j.gastro.2020.11.051

2. Åberg F, Puukka P, Salomaa V, et al. Risks of light and moderate alcohol use in fatty liver disease: follow-up of population cohorts. Hepatology. 2020;71(3):835-848.