Effect of Endoscopic Sleeve Gastroplasty in Patients With Obesity and MASH: A Randomized Controlled Trial

Inclusion Criteria: 1. Age ≥ 18 (male or female) 2. BMI ≥30 kg/m2 or ≥27 kg/m2 with at least one obesity-related comorbidity 3. Self-reported stable weight (no weight change \>5%) for 6 months prior to the first study visit 4. Willingness to follow protocol requirements, including signed informed consent, routine follow-up schedule, completing laboratory/imaging/additional tests, and completing diet counseling 5. Willingness to NOT start a new anti-obesity medication for the following 12 months 6. Residing within a reasonable distance from the investigator's office and able to travel to the investigator to complete routine follow-up visits 7. Ability to give informed consent 8. Women of childbearing potential (i.e., not post-menopausal, nor surgically sterilized) must agree to use adequate birth control methods Exclusion Criteria: 1. Known history of other chronic liver diseases (viral hepatitis, autoimmune hepatitis, drug-induced hepatitis, and genetic) 2. Treatment with vitamin E (at doses ≥800 IU/day), pioglitazone, obeticholic acid, or resmetirom \<90 days before the first study visit 3. History of foregut or gastrointestinal (GI) surgery (except uncomplicated fundoplication, cholecystectomy or appendectomy) 4. Prior bariatric surgery 5. Prior endoscopic sleeve gastroplasty 6. Any inflammatory disease of the GI tract, including severe (LA Grade C or D) esophagitis, Barrett's esophagus with dysplasia, gastric ulceration, duodenal ulceration, cancer or specific inflammation such as Crohn's disease 7. Potential upper gastrointestinal bleeding conditions such as esophageal or gastric varices, congenital or acquired intestinal telangiectasis, or other congenital anomalies of the gastrointestinal tract such as atresias or stenoses 8. Severe gastroesophageal reflux disease (GERD) 9. A structural abnormality in the esophagus or pharynx, such as a stricture or diverticulum, that could impede passage of the endoscope. 10. Achalasia or any other severe esophageal motility disorder 11. Chronic abdominal pain 12. Gastroparesis or intractable constipation 13. Hepatic insufficiency or cirrhosis 14. Severe coagulopathy 15. Insulin-dependent diabetes (either type 1 or type 2) or a significant likelihood of requiring insulin treatment in the following 12 months or HgbA1C ≥ 12% 16. Patients on an anti-platelet agent, anticoagulant agent or chronic/routine use of NSAIDs 17. Patients on corticosteroids, immunosuppressants, or narcotics 18. Patients on an anti-seizure or anti-arrhythmic medication 19. Patients who are pregnant or breastfeeding 20. Excessive alcohol consumption (\>20 g per day for women; \>30 g per day for men) 21. Active smoking 22. History of poorly controlled hypertension, coronary artery disease, congestive heart failure, cardiac arrhythmia 23. History of respiratory diseases such as chronic obstructive pulmonary disease (COPD) requiring steroids, pneumonia, or cancer 24. History of autoimmune connective tissue disorder such as lupus, scleroderma or immunocompromised disease 25. History of active malignancy 26. History of genetic or hormonal causes for obesity, such as Prader Willi syndrome 27. History of endocrine disorders affecting weight, such as uncontrolled hypothyroidism 28. Eating disorders, including night eating syndrome, bulimia, binge eating disorder or compulsive overeating 29. Active psychological issues preventing participation in a lifestyle modification program as determined by a psychologist