The Efficacy of Pedometer-motivated Physical Activity for the Management of Patients With MASLD.

The Efficacy of Pedometer-motivated Physical Activity for the Management of Patients With Metabolic-associated Steatotic Liver Disease: a Randomized-controlled Trial

The study conducted a health survey among Thai adults in 2022 and found a significant increase in obesity and nonalcoholic fatty liver disease (NAFLD), leading to metabolic-associated steatotic liver disease (MASLD). The prevalence of NAFLD was 19.7%, with higher rates in individuals with metabolic syndrome and diabetes. MASLD is associated with insulin resistance and genetic polymorphisms, particularly the patatin like phospholipase domain containing 3-rs738409 variant. Additionally, physical activity was inversely related to liver disease risk, with higher step counts associated with reduced incidence of NAFLD and liver-related mortality. The study aims to investigate the impact of dietary advice and pedometer use on physical activity levels and health outcomes in MASLD patients over 24 weeks.

The results of the health survey of the Thai population through physical examinations in the year 2022 found that among Thai people aged 18 and older, the prevalence of obesity (BMI ≥25 kg/m2) was 44.9% (40.3% in males and 49.2% in females), which has increased significantly over the past decades. This condition is a significant factor contributing to the rising incidence of nonalcoholic fatty liver disease (NAFLD) among the Thai population. NAFLD refers to fatty liver disease in individuals who consume alcohol in amounts less than 140 grams per week for females or less than 210 grams per week for males. Those with clinical features of metabolic dysfunction have been newly defined as having metabolic-associated steatotic liver disease (MASLD).

In this survey of 18,588 individuals, the prevalence of NAFLD was 19.7%, with rates of 20.9% in males and 18.6% in females. It was notably higher at 43.5% in individuals with abdominal obesity (metabolic syndrome) and 35.6% in individuals with diabetes. Factors such as age, sex, physical activity, smoking, and metabolic characteristics such as overweight or obesity, abdominal obesity, high triglyceride levels, diabetes, hypertension, and low HDL cholesterol levels are significantly associated with NAFLD.

MASLD, a type of fatty liver disease, is directly associated with insulin resistance, a key risk factor for cardiovascular diseases. Current treatment guidelines for MASLD have clear evidence that weight loss through dietary control and appropriate physical activity or exercise can reduce fat accumulation in the liver, inflammation, and fibrosis. Importantly, it also improves various metabolic parameters such as blood sugar and lipid levels, as well as the effectiveness of insulin.

The etiology of MASLD is related to behavioral and environmental factors, such as high-calorie diets combined with low physical activity and sedentary lifestyles. These factors promote insulin resistance, stimulating lipolysis and the movement of free fatty acids to various organs, including the liver. This leads to fat accumulation in the liver, insulin-resistant hepatic tissue, abnormal β-oxidation processes, oxidative stress, hepatic inflammation, increased stellate cell activation, and subsequent fibrosis, eventually increasing the risk of liver cirrhosis and hepatocellular carcinoma.

Genetic polymorphisms play a significant role in MASLD pathogenesis, with single nucleotide polymorphisms (SNPs) in the patatin like phospholipase domain containing-3 gene, particularly the rs738409 variant, being strongly associated with fat accumulation and fibrosis in the liver.

Furthermore, a systematic review and analysis of data from 12 studies involving 111,309 individuals found that the number of steps per day, particularly 8,800 steps per day, was associated with a significant reduction in the risk of overall mortality and cardiovascular diseases (CVD). Additionally, increasing physical activity was associated with a reduced risk of chronic liver disease overall and NAFLD specifically. Increasing physical activity by 2,500 steps per day was associated with a 38% reduction in chronic liver disease and a 47% reduction in NAFLD, regardless of obesity status.

This research aims to conduct a randomized study to provide advice to MASLD patients to modify their diet and wear pedometers to encourage changes in physical activity, with a goal of achieving at least 8,800 steps per day, compared to MASLD patients who only receive dietary advice and wear pedometers to record daily steps over a 24-week period.

Inclusion Criteria:

1. Participants must be diagnosed with MASLD according to the diagnostic criteria of the A multi-society Delphi consensus statement on new fatty liver disease nomenclature 2023, with evidence of hepatic steatosis and alcohol consumption of less than 140 grams per week for females or less than 210 grams per week for males, along with at least one of the clinical characteristics of metabolic syndrome.
2. Participants must be at least 18 years old at the time of enrollment.
3. Patients must consent to blood testing for the identification of the patatin like phospholipase domain containing-3 gene polymorphism.

Exclusion Criteria:

1. Individuals who engage in regular exercise for at least 20 minutes per day, at least 3 days per week.
2. Individuals who have regular physical activity with walking exceeding 3000 steps per day before participating in the study.
3. Individuals diagnosed with other chronic liver diseases such as hepatitis B or C, autoimmune hepatitis, Wilson's disease, liver cancer, hemochromatosis, liver cirrhosis, or others.
4. Individuals diagnosed with diseases that may affect non-alcoholic fatty liver disease, such as HIV, various chronic inflammatory diseases, or connective tissue disorders.
5. Individuals taking medications known to promote fatty liver disease, including amiodarone, steroids, methotrexate, hormonal medications, or immunosuppressants.
6. Individuals who have previously taken medications known to impact fatty liver disease, including vitamin E, pioglitazone, Glucagon-like peptide-1 agonists, SGLT2 inhibitors.
7. Participants intending to join weight loss programs or undergo bariatric surgery for obesity treatment.
8. Individuals with cirrhosis.
9. Individuals diagnosed with liver cancer.
10. Individuals with severe chronic diseases still exhibiting symptoms during physical activity that may exacerbate the disease, such as coronary artery disease, chronic obstructive pulmonary disease, or severe osteoarthritis.
11. Patients with contraindications for undergoing MRI examinations, such as claustrophobia or having body implants or materials that are incompatible with MRI scanning.
12. Women who are pregnant.
13. Individuals who do not provide formal consent to participate in the research project.