Editor’s Note Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease worldwide, with recent data showing prevalence rates of up to 39% in adults and 20% in children. MAFLD is characterized by overweight or obesity, type 2 diabetes, and/or metabolically dysregulated hepatic steatosis and can coexist with various hepatic and cardiovascular metabolic diseases.
It is noteworthy that MAFLD patients are at higher risk for cardiovascular disease and overall mortality, with potentially poorer disease outcomes. As the prevalence, health burden, and socioeconomic impact of MAFLD increase, there is a growing need for novel lifestyle approaches and multidisciplinary care to maintain healthy lifestyles for MAFLD patients. Additionally, individualized specialized care is required due to the various subtypes of MAFLD.
Recently, Hepatology International published a review on lifestyle interventions for MAFLD. The researchers combined past and recent evidence to provide clinical guidelines for lifestyle management of adult MAFLD. They also aimed to explore effective contemporary lifestyle interventions for MAFLD through the specific lens of a “24-hour” integrated lifestyle approach, including diet, physical activity, sedentary behavior, substance use, and sleep.
Goals of Lifestyle Interventions
Researchers emphasized that improving diet quality, increasing physical activity, reducing or eliminating alcohol consumption, and quitting smoking have multiple benefits for the liver and overall health. Lifestyle interventions can halt the progression of MAFLD, reverse MAFLD histologically, and reduce the incidence of hepatocellular carcinoma. Additionally, lifestyle changes can lower the risk of cardiometabolic diseases, reduce cardiovascular morbidity, and decrease mortality.
From a patient-centered perspective, improving quality of life is the primary goal of lifestyle interventions. Lifestyle management should be conducted by a multidisciplinary care team, including physicians, dietitians, exercise professionals, psychologists, nurses, and other specialized healthcare professionals.
Weight Management
MAFLD’s metabolic dysfunction is closely related to excess and dysfunctional adipose tissue, making weight loss (especially fat loss) central to MAFLD management. The degree of weight loss is proportional to improvements in liver-related outcomes. Current guidelines recommend a weight loss of ≥5% to reduce hepatic steatosis, ≥7% to alleviate steatohepatitis, and ≥10% to resolve fibrosis.
However, achieving and maintaining a weight loss of ≥7% to 10% is challenging, with less than one-third of MAFLD patients achieving ≥5% weight loss through lifestyle interventions within 52 weeks. Additionally, 5% to 10% of MAFLD patients have a normal body mass index (BMI; <25 kg/m2 for Western populations, <23 kg/m2 for Asian populations), with the highest incidence among middle-aged individuals in Asian countries. For lean MAFLD patients, a 3% to 5% weight loss can lead to MAFLD resolution in 50% of cases and improve cardiometabolic health.
Regardless of weight loss, lifestyle interventions benefit overall health. A reduction in hepatic steatosis of ≥30% is associated with clinically significant improvements in MAFLD activity scores. There is a strong correlation between weight loss and the reduction of hepatic steatosis, with an average weight loss of ≤5% through lifestyle interventions resulting in a relative reduction in hepatic steatosis of ≥30%. Therefore, appropriate behavioral strategies should emphasize health goals beyond weight loss, tailored to the patient’s performance, capabilities, and preferences.
Diet Management and Smoking
Current clinical management guidelines, including those from major international associations, provide dietary recommendations for MAFLD. All guidelines advise against alcohol consumption, as it affects fibrosis and the progression of end-stage liver disease, recommending consumption below risk thresholds (women: 20 g/day, men: 30 g/day) or complete abstinence, especially for patients with severe fibrosis (＞F2) and/or moderate to heavy drinking.
Dietary recommendations prioritize calorie restriction for weight loss and enhancing anti-inflammatory and antioxidant dietary intake to control disease onset and progression.
Moreover, smoking is a known risk factor for various chronic diseases, including cardiovascular diseases and cancers, common causes of MAFLD morbidity and mortality. Smoking is associated with advanced fibrosis in chronic liver diseases like chronic viral hepatitis. Studies also show a dose-dependent relationship between smoking and the stage of liver fibrosis in MAFLD patients. In fact, a recent study in Spain demonstrated that smoking increases overall mortality in MAFLD patients.
Physical Activity Management
Physical activity (PA) and sedentary behavior are linked to the development of MAFLD. Increased PA is associated with a dose-dependent reduction in MAFLD risk. In the UK Biobank, those in the highest PA quartile had a 61% lower risk of MAFLD than those in the lowest quartile. Additionally, increased daily step counts are related to reduced MAFLD risk and liver disease progression. Higher PA levels may limit the expression of genetic risk factors for progressive MAFLD (PNPLA3, rs738409). Sedentary behavior and sedentary time are independent predictors of MAFLD and show a dose-dependent relationship; every additional hour of sitting per day increases the likelihood of MAFLD by 4%.
Individuals sitting ≥7 hours/day are 34% more likely to have MAFLD compared to those sitting ≤4 hours/day. Additionally, sitting ≥8 hours/day may increase MAFLD risk, independent of PA levels. Moderate to vigorous PA is associated with MAFLD resolution. In a large adult cohort, 35% of baseline MAFLD cases (n=42,536) resolved after a 5-year follow-up. Moderate to vigorous PA was associated with MAFLD resolution after adjusting for BMI and other confounding factors, with benefits maximized when PA frequency was ≥5 days/week. Notably, compared to non-MAFLD patients, MAFLD patients have more sedentary time and are less likely to meet recommended PA guidelines, with 75% to 80% of MAFLD patients being physically inactive.
Sleep Management
Few studies have investigated the impact of sleep quality and duration on MAFLD. A review including five cross-sectional studies and one cohort study found that shorter sleep duration (<5-6 hours) increased the risk of MAFLD by 19%. A larger cohort study confirmed these findings, with an average follow-up of 4 years. MAFLD patients had poorer sleep efficiency, more frequent daytime naps (>30 minutes), higher use of sleeping pills, and later bed and wake times compared to non-MAFLD patients.
Data suggest that optimal sleep duration of 7-8 hours and reducing daytime napping may help prevent MAFLD. However, the impact of sleep on inflammatory processes, hormone-driven appetite regulation, metabolism, and fatigue affecting physical activity and dietary choices warrants further research.
Summary and Outlook
Achieving a weight loss of ≥7% to 10% is a core goal of lifestyle interventions. However, even without weight loss, improving diet quality and engaging in exercise offer benefits.
Lifestyle interventions for MAFLD should consider the “24-hour” approach, encompassing diet, physical activity/exercise, sedentary behavior, smoking, alcohol consumption, and sleep management. Dietary management should focus on energy restriction and improving diet quality, with a particular emphasis on the Mediterranean diet, tailored to different dietary cultures.
Increasing physical activity and reducing sedentary behavior can prevent MAFLD. The strongest evidence supports 150-240 minutes of moderate-intensity aerobic exercise per week. For individuals losing weight through diet and/or medications and those with sarcopenia, resistance training in addition to aerobic exercise should be prioritized to prevent skeletal muscle loss. Limited evidence suggests sleep is crucial for preventing MAFLD.
Researchers advocate for large-scale multidisciplinary trials with long-term follow-up for MAFLD patients to extend the 24-hour comprehensive lifestyle behavior management recommendations to basic healthcare. Future MAFLD management guidelines should consider the heterogeneity and individualized care models of MAFLD to better manage the growing number of MAFLD patients.
Original Article Link: Keating, S.E., Chawla, Y., De, A. et al. Lifestyle intervention for metabolic dysfunction-associated fatty liver disease: a 24-h integrated behavior perspective. Hepatol Int (2024).
