Hepatic Elastography-Enhanced Lifestyle Modification in MASLD

Official title

Hepatic Elastography-Enhanced Lifestyle Modification in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomized Controlled Trial

Overview

The 2022 National Health Survey in Thailand revealed a substantial rise in obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). The prevalence of MASLD was 19.7%, with higher rates observed in individuals with metabolic syndrome and diabetes. Effective management of MASLD primarily involves lifestyle modifications, including dietary adjustments and increased physical activity. Evidence suggests that patients unaware of their liver fibrosis status are less likely to adhere to these interventions. This study aims to evaluate the impact of hepatic elastography monitoring on lifestyle modification adherence and health outcomes in patients with MASLD over 48 weeks.

Detailed description

The 2022 health survey of Thai adults (aged ≥18 years) reported an obesity prevalence of 44.9% (40.3% in males, 49.2% in females), a significant increase over past decades. Obesity is a major contributing factor to the rising incidence of MASLD, previously termed nonalcoholic fatty liver disease (NAFLD). MASLD is defined as fatty liver disease occurring in individuals consuming less than 140 grams of alcohol per week for females or less than 210 grams per week for males, alongside clinical features of metabolic dysfunction.

Among 18,588 surveyed individuals, the prevalence of MASLD was 19.7% (20.9% in males, 18.6% in females), with notably higher rates of 43.5% in those with abdominal obesity and 35.6% in individuals with diabetes. Significant associations were observed between MASLD and factors such as age, sex, physical activity, smoking, and metabolic abnormalities, including overweight, abdominal obesity, elevated triglycerides, diabetes, hypertension, and low HDL cholesterol levels.

MASLD is closely linked to insulin resistance, a critical risk factor for cardiovascular disease. Current guidelines emphasize weight loss through dietary control and exercise to reduce hepatic fat accumulation, inflammation, and fibrosis, while improving metabolic parameters such as blood glucose, lipid profiles, and insulin sensitivity. Behavioral and environmental factors, including high-calorie diets and sedentary lifestyles, contribute to the pathogenesis of MASLD by promoting insulin resistance and hepatic fat accumulation, leading to oxidative stress, inflammation, and fibrosis, thereby increasing the risks of cirrhosis and hepatocellular carcinoma.

A recent study highlighted that 59.2% of MASLD patients were unaware of their liver fat and fibrosis status. Lack of awareness was associated with poor adherence to lifestyle modifications, particularly in obese individuals (BMI \> 30 kg/m²). This randomized controlled trial investigates the effect of hepatic elastography monitoring on lifestyle changes, hepatic steatosis, metabolic parameters, and anthropometry, compared to standard care over a 48-week period.

Interventions

• Other Regular monitoring with transient elastography
  MASLD patients were received their liver fat and fibrosis status regularly using transient elastography

Primary outcome measures

• Change from baseline in non-invasive marker magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) (%) [Time frame: 48 weeks]

Secondary outcome measures (9)

• Change from baseline in non-invasive liver fibrosis marker [Time frame: 48 weeks]
• Change from baseline in markers of liver injury [Time frame: 48 weeks]
• Change from baseline in markers of glycemic control [Time frame: 48 weeks]
• Change from baseline in Hemoglobin A1C (%) [Time frame: 48 weeks]
• Change from baseline in lipoproteins [Time frame: 48 weeks]
• Change from baseline in body fat composition assessed by Bioelectrical Impedance Analysis [Time frame: 48 weeks]
• Change from baseline in muscle mass assessed by Bioelectrical Impedance Analysis [Time frame: 48 weeks]
• Change from baseline in visceral fat assessed by Bioelectrical Impedance Analysis [Time frame: 48 weeks]
• Change from baseline in wieght in kilograms assessed by Bioelectrical Impedance Analysis [Time frame: 48 weeks]

Eligibility criteria

Inclusion criteria

• Participants must be diagnosed with MASLD according to the diagnostic criteria outlined in the 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 clinical characteristic of metabolic syndrome.
• Participants must be at least 18 years old and less than 80 years old at the time of enrollment.

Exclusion criteria

• Individuals diagnosed with other chronic liver diseases, including hepatitis B or C, autoimmune hepatitis, Wilson's disease, liver cancer, hemochromatosis, or liver cirrhosis.
• Individuals diagnosed with conditions that may influence MASLD, such as HIV, chronic inflammatory diseases, or connective tissue disorders.
• Individuals taking medications known to promote fatty liver disease, such as amiodarone, steroids, methotrexate, hormonal medications, or immunosuppressants.
• Individuals who have previously taken medications known to impact fatty liver disease, including vitamin E, pioglitazone, GLP-1 receptor agonists, or SGLT2 inhibitors.
• Participants intending to join weight loss programs or undergo bariatric surgery for obesity treatment.
• Individuals with severe chronic diseases presenting symptoms during physical activity, such as coronary artery disease, chronic obstructive pulmonary disease, or severe osteoarthritis, which may exacerbate their condition.
• Patients with contraindications to undergoing MRI examinations, such as claustrophobia or incompatible body implants or materials.
• Women who are pregnant.
• Individuals who do not provide formal consent to participate in the research project.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Thailand · 1 center

• Faculty of Medicine Siriraj Hospital, Mahidol University — Bangkoknoi

Publications

• Sheka AC, Adeyi O, Thompson J, Hameed B, Crawford PA, Ikramuddin S. Nonalcoholic Steatohepatitis: A Review. JAMA. 2020 Mar 24;323(12):1175-1183. doi: 10.1001/jama.2020.2298. PMID 32207804
• Koolhaas CM, van Rooij FJ, Cepeda M, Tiemeier H, Franco OH, Schoufour JD. Physical activity derived from questionnaires and wrist-worn accelerometers: comparability and the role of demographic, lifestyle, and health factors among a population-based sample of older adults. Clin Epidemiol. 2017 Dec 18;10:1-16. doi: 10.2147/CLEP.S147613. eCollection 2018. PMID 29296097
• Joo JH, Kim HJ, Park EC, Jang SI. Association between sitting time and non-alcoholic fatty live disease in South Korean population: a cross-sectional study. Lipids Health Dis. 2020 Sep 23;19(1):212. doi: 10.1186/s12944-020-01385-6. PMID 32967678
• Mansour-Ghanaei R, Mansour-Ghanaei F, Naghipour M, Joukar F. The Lifestyle Characteristics in Non-Alcoholic Fatty Liver Disease in the PERSIAN Guilan Cohort Study. Open Access Maced J Med Sci. 2019 Sep 14;7(19):3313-3318. doi: 10.3889/oamjms.2019.647. eCollection 2019 Oct 15. PMID 31949537
• Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, Kleiner DE, Loomba R. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023 May 1;77(5):1797-1835. doi: 10.1097/HEP.0000000000000323. Epub 2023 Mar 17. No abstract available. PMID 36727674
• Akuta N, Kawamura Y, Arase Y, Suzuki F, Sezaki H, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Suzuki Y, Ikeda K, Kumada H. Relationships between Genetic Variations of PNPLA3, TM6SF2 and Histological Features of Nonalcoholic Fatty Liver Disease in Japan. Gut Liver. 2016 May 23;10(3):437-45. doi: 10.5009/gnl15163. PMID 26610348
• Carrieri P, Mourad A, Marcellin F, Trylesinski A, Calleja JL, Protopopescu C, Lazarus JV. Knowledge of liver fibrosis stage among adults with NAFLD/NASH improves adherence to lifestyle changes. Liver Int. 2022 May;42(5):984-994. doi: 10.1111/liv.15209. Epub 2022 Mar 7. PMID 35220673
• Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, Romero D, Abdelmalek MF, Anstee QM, Arab JP, Arrese M, Bataller R, Beuers U, Boursier J, Bugianesi E, Byrne CD, Castro Narro GE, Chowdhury A, Cortez-Pinto H, Cryer DR, Cusi K, El-Kassas M, Klein S, Eskridge W, Fan J, Gawrieh S, Guy CD, Harrison SA, Kim SU, Koot BG, Korenjak M, Kowdley KV, Lacaille F, Loomba R, Mitchell-Thain R, Mo PMID 37363821

Identifiers

NCT: NCT06826807 · SI 009/2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗