Management of non-alcoholic fatty liver disease: Lifestyle changes

Abstract

In this editorial, we commented on a recently released manuscript by Zeng et al in the World Journal of Gastroenterology. We focused specifically on lifestyle changes in patients with non-alcoholic fatty liver disease (NAFLD). NAFLD is a hepatic manifestation of the metabolic syndrome, which ultimately leads to advanced hepatic fibrosis, cirrhosis, and hepatocellular carcinoma and affects more than 25% of the population globally. Existing therapeutic strategies against NAFLD such as pharmacologic therapies focus on liver protection, anti-inflammation, and regulating disease-related metabolic disorder symptoms. Although several drugs are in late-stage development, potent drugs against the diseases are lacking. Additionally, existing surgical approaches such as bariatric surgery are not routinely used to treat NAFLD. Intervening in patients’ unhealthy lifestyles, such as weight loss through dietary changes and exercises to ameliorate patient-associated metabolic disorders and metabolic syndrome, is the first-line treatment for patients with NAFLD. With sufficient intrinsic motivation and adherence, the management of unhealthy lifestyles can reduce the severity of the disease, improve the quality of life, and increase the survival expectancy of patients with NAFLD.

Key Words: Non-alcoholic fatty liver disease; Lifestyle; physical activity; Physical exercise; Low-calorie diet; Mediterranean diet

Core Tip: With a worldwide prevalence of 25%, non-alcoholic fatty liver disease (NAFLD) is a leading cause of cirrhosis and hepatocellular carcinoma. NAFLD is bi-directionally associated with the metabolic syndrome. Owing to the lack of specific drugs and conventional surgeries to treat NAFLD, correcting the unhealthy lifestyles of patients with NAFLD by opting for dietary changes and exercises is the first line of intervention to alleviate pain and improve the quality of life of the patients provided that the patients are intrinsically motivated and adherent.

INTRODUCTION

Non-alcoholic fatty liver disease (NAFLD), an epidemic liver disease of the 21^st century, is manifested by metabolic disorders and is the leading cause of chronic liver disease, affecting more than 25% of the global population[1]. Additionally, NAFLD is associated with increased mortality owing to cardiovascular diseases (CVDs), diabetes, and pulmonary diseases, including obstructive sleep apnea[2]. Its exact pathogenesis has not been elucidated; however, risk factors associated with it include unhealthy lifestyle, insulin resistance (IR), type 2 diabetes mellitus (T2DM), increased hepatic lipogenesis, and intestinal dysbiosis[3]. Nevertheless, standard therapies for NAFLD are not available, and only a few pharmacologic options are available for these patients; currently, the European and American Association for the Study of the Liver recommend administering only vitamin E and pioglitazone (the proliferation-activated receptor γ ligand) to specific patients[4]. Additionally, bariatric surgery improves NAFLD in patients with NAFLD complicated with obesity[4,5]. This may be correlated to the higher remission rates of T2DM after bariatric surgery; however, NAFLD itself is not currently an indication for bariatric surgery[5].

Lifestyle changes, such as substantial weight loss by consuming low-calorie diets and engaging in physical activities, are considered first-line interventions for treating NAFLD because weight loss is correlated to liver fat reduction, which may reverse disease progression[6,7]. Consequently, the American Gastroenterological Association has provided recommendations for treating patients with obesity as well as for safe and effective weight control. These recommendations are based on four guiding principles, namely assessment, intensive weight loss interventions, weight stabilization, and weight loss re-enforcement if necessary, and weight rebound prevention, to achieve weight loss through low-calorie diets, physical activities, medications, bariatric endoscopy, and surgery[8]. However, medications, bariatric endoscopy, and surgery are primarily for patients who are severely obese and have concomitant diabetes mellitus (DM), biopsy-proven NAFLD, and at least stage 2 liver fibrosis[8]. NAFLD is not limited to patients with obesity, and the prevalence of normal-weight NAFLD in the general population may range from 4% to 10%[9]. However, depending on the number of metabolic disorders present, patients with NAFLD complicated with obesity carry a higher burden of morbidity and mortality[9]. Therefore, in the context of increased NAFLD, obesity, and metabolic syndrome incidence and prevalence, reducing body weight through lifestyle changes by consuming an appropriate diet and doing exercises remains the cornerstone of NAFLD treatment[8].

Finally, improving adherence and intrinsic motivation to make lifestyle changes is crucial from the viewpoint of patients with NAFLD. Scarce data exist on the persistence of the metabolic effects of diet and exercise; however, most patients with NAFLD cannot adhere to lifestyle changes to lose weight[10]. Zeng et al[11] developed and validated the Exercise and Diet Adherence Scale (EDAS) to rapidly assess adherence to lifestyle interventions in patients with NAFLD. Patients were grouped according to EDAS scores and received individualized treatment accordingly, which improved their adherence to lifestyle interventions[11].

PRACTICAL RECOMMENDATIONS FOR CHANGING LIFESTYLES

NAFLD is strongly correlated to obesity in most populations irrespective of histologic type, and lifestyle intervention aimed at weight loss and exercise are the mainstay of the treatment[1,6,12]. Weight loss reduces liver fat, improves glycemic control/insulin sensitivity, and reduces the risk of diabetes, CVD, and worsening liver disease[6]. Current guidelines from the American Gastroenterological Association recommend at least 5% weight loss to reduce hepatic steatosis and 10% weight loss to reverse liver fibrosis. Additionally, weight loss of ≥ 7% may regress non-alcoholic steatohepatitis[13]. For adults with NAFLD who are not overweight or obese, a weight loss of 3%-5% is recommended[6,13].

A low-calorie diet is critical in NAFLD treatment. A low-calorie diet is characterized by reducing calorie intake by 500-1000 kcal/d, resulting in intake of up to 1200 kcal/d for women and 1400-1500 kcal/d for men. Such a diet is associated with weight loss, improved IR, and reduced intrahepatic fats[2,14]. Improvements in intrahepatic fat levels persist after consuming a low-calorie diet, even when weight is regained after 2 years of weight loss[15]. Additionally, diets containing specific macronutrients are good options, including low-carbohydrate and Mediterranean diets (Med diet, MD)[16]. An MD is characterized by daily consumption of fresh vegetables, fruits, legumes, minimally processed whole grains, fish (rich in omega-3 fatty acids), olive oil, nuts, and seeds, which are the primary sources of fat[16]. As a primary source of fat, minimize or avoid dairy products, red meat, and processed meats. The American College of Cardiology, the American Heart Association, and the Office of Disease Prevention and Health Promotion support the use of an MD in preventing and controlling CVDs, which is critical for patients with NAFLD, which is closely related to CVD occurrence. Moreover, MD consumption is associated with a reduced risk of hepatocellular carcinoma (HCC)[17]. In addition to DM, the consumption of a ketogenic diet (KD) is a recommended dietary intervention for NAFLD treatment. KD, which comprises a high proportion of fat and a low proportion of carbohydrates, proteins, and other nutrients, plays a positive role in NAFLD treatment owing to the extremely low proportion of carbohydrates. KD consumption markedly alters mitochondrial flux and hepatic redox status and promotes ketone body production without affecting intrahepatic triglyceride synthesis, thus considerably improving visceral fat content[18]. Although KD consumption exerts some therapeutic effects on patients with NAFLD, tests on animals and clinical studies have indicated some risks associated with it, and existing clinical trials suggest that the safety of KD in treating NAFLD should be investigated further[19]. Additionally, new dietary interventions have been used to progressively treat patients with NAFLD. For instance, high-protein (animal- or plant-based) diets can markedly decrease inflammatory marker levels[20]. An eight-week sugar-restricted diet reduced liver fat and improved liver steatosis in adolescent boys with NAFLD[21]. However, owing to the limited number of clinical trials on these dietary interventions, adequate conclusions are not drawn. Similarly, interventions such as intermittent fasting and time-restricted eating have limited clinical evidence and inconclusive results; thus, their safety and efficacy cannot be proven as of now.

Exercise improves impaired glucose and lipid metabolism and is an effective intervention for treating metabolic diseases[22]. Engaging in exercise may enhance the beneficial effects of a low-calorie diet on NAFLD. Furthermore, it may improve the course of NAFLD by reducing hepatic fat levels via increasing insulin sensitivity in the periphery of the body and decreasing hepatic neolipogenesis, lipolysis in adipocytes, and free fatty acid delivery to the liver. Physical activity can be achieved through aerobic exercise (e.g., walking or bicycling), and resistance training can be achieved through weight-bearing exercise (e.g., weight training on an exercise machine)[23]. Generally, 90-300 min of physical activity per week is beneficial for steatosis, and patients should consider 150-300 min of moderate-intensity exercise (3-6 metabolic equivalents) or 75-150 min of vigorous exercise (more than 6 metabolic equivalents). Compared with aerobic exercise, resistance training reduces steatosis; however, it is less intense and may be suitable for individuals with limited aerobic capacity[24]. However, a recent population-based study showed that walking more than 3 h/wk was correlated to reduced mortality from cirrhosis and HCC; thus, consideration should be given to encouraging aerobic exercise[24]. Exercise may enhance the effect of diet on weight loss; thus, moderate physical activity combined with an MD may result in weight loss and visceral adipose tissue and intrahepatic fat percentage reduction[22-24].

Lifestyle interventions for patients with NAFLD should include diverse general health-related behaviors. Smoking and alcohol consumption are risk factors that can accelerate liver disease progression and are synergistic with other risk factors[25]. Even light-to-moderate alcohol consumption (≤ 1 drink per day for women and ≤ 2 drinks per day for men; 1 drink is equivalent to 1 regular beer (12 ounces), 1 glass of wine (5 ounces), or 1 glass of white wine or spirits (1.5 ounces)) is associated with steatosis and hepatic fibrosis progression and exerts a synergistic effect on the risk of obesity and the development of numerous clinical liver diseases, including cirrhosis and liver cancer)[26]. Therefore, counseling and interventions should be considered to help smokers quit smoking and alcohol drinkers reduce or stop drinking, especially if they have liver fibrosis[27].

Adherence to lifestyle changes is crucial for patients with NAFLD as most of whom face challenges while sustainably changing their habits[10]. Zeng MH et al[11] provide important help on how to effectively improve the adherence of such patients to lifestyle modifications. They designed the EDAS for patients with NAFLD aged 18-70 years who were admitted to Tianjin Second People’s Hospital from August 2013 to January 2014 (study subjects). They first identified factors affecting exercise and diet adherence in patients with NAFLD as well as analyzed and modified the EDAS using the Delphi method. After establishing the EDAS, patients with NAFLD were initially entered into the EDAS system as the target population for exercise and diet interventions and followed up for 6 months. The EDAS exhibited good item discrimination, internal consistency, reliability, retest reliability, content validity, structural validity, and criterion validity and could reliably measure adherence to exercise and dietary interventions in the patients. Thus, this scale allows patients to be grouped according to EDAS scores and helps recommend personalized treatments accordingly, thus improving adherence to lifestyle interventions[11].

CONCLUSION

Pharmacologic treatment options for patients with NAFLD are scarce, and surgery is not a routinely followed treatment modality[4]. Consequently, lifestyle modifications, including consuming a healthy diet and engaging in physical activity to lose weight and improve metabolic disorders, are the cornerstone of NAFLD treatment[6]. Furthermore, limiting or avoiding alcohol consumption and smoking is essential[26]. Additionally, some patients do not adhere well to the discussed lifestyle interventions; thus, improving their adherence to lifestyle modifications is equally important. Nevertheless, we should continue developing comprehensive interventions to help patients with NAFLD manage their lifestyles, improve nutrition, lose weight, and ultimately change their health trajectories to improve their quality of life and increase survival expectations.