Table 3.

Treatments for Obesity and MAFLD, Considering Pathological Processes That are Targets for Therapy

Intervention	Classification	Mechanism	Mean %TBWL	Liver Fat Improvement	NAS improvement/Indicators of Liver Enzymology	NFS/LS Improvement	INS or T2DM Improvement
Lifestyle Modifications (weight loss)	Calorie-restricted interventions103	Calorie-restricted		HS (p < 0.001)103	Effects on ALT reduction (p< 0.001)103	LS (p= 0.009).
	Mediterranean diet’s macronutrient104,105	Impact of the macronutrient profile	No105	MED/LC induced a greater %HFC decrease (p= 0.036)104 Decrease in IHL (%) than LF/HCD (p = 0.03).105	Reduced GGT, ALT (p <0.05)104; Reduced ALT (p= 0.02)103	LS (p= 0.05).103	GHb (p <0.05)104 Decrease in HOMA-IR Insulin concentration decline (p= 0.008)105
	Aerobic physical activity	150 minutes each week; more than 10,000 steps per day, more than a year, higher amounts of physical activity-between 200 and 300 minutes per week.106	At least weight loss of 7% (usually greater than 10%)106
Antiobesity Pharmacotherapy	Liraglutide 3.0 g	GLP-1 analog inhibits food intake by inducing 51 s107	8.0% vs 2.6% after 56 wk107	Steatosis improvement 83%vs.45% (p=0.009)107	-1.3 change in NAS score and 74% had NAS im- provement. 39% had complete resolution.107	-0.2 change in fibrosis (p= 0.11).107	-5.18 change in HbA1C (p= 0.03)
	Semaglutide 0.4 mg	Long-acting GLP-1 analog inhibits food intake by inducing satiety108	-13 vs.-1% after 72 wk		-59 vs -17% after 72 wk.	43% had an improvement in fibrosis stage in the 0.4-mg group and 33% in the placebo group (p= 0.48).	GHb level among patients with T2DM -1.07 in the 0.2-mg group and -0.01 in the placebo group
	Orlistat	Reversible pancreatic lipase inhibitor, decreasing the hydrolysis of intestinal fat, therefore, absorpt109	-8.3 vs.-6% after 36 wk.109	LFC-9.1% 24 weeks110	No111	-0.14 change in fibrosis.111	HOMA-IR -1.05; P=0.04111
Bariatric Endoscopic Interventions	IGB	Introducing an empty balloon into the stomach through an upper endoscopy. The balloon is inflated with air or saline to reduce the stomach volume. This will result in early satiety and weight loss.112	-11.7%after 6 mo.113 Average reduction in participant body weight of 11.9 kg		90% had 3 points improvement in their NAS.113 Improvement (p=0.03) in the NAS.114 83.5% of patients’ NAS scores had improved115	1.17 stages improvement in 15% of participants in NFS.113
	ESG	A minimally invasive bariatric procedure that is done through endoscopically inserting a suturing device to remodel the greater curvature Of the stomach.116	-14.9% after 6 mo.		4.0 points per year using HSI.117	20% had significant improvement in NFS (from F3-F4 indeterminate to F0-F2).117 0.3 points annually following the procedure.117
	DMR	By modifying, eliminating, or omitting duodenal exposure to intra-luminal nutrients, favorable metabolic effects were seen.118	Three months of DMR decreased by 3.1 kg (p<0.001)119				HbA1C levels dramatically decreased by 1.72% (p=0.02)119
Bariatric Surgical Intervention	SG	A restrictive bariatric procedure that involves resection of two-thirds of the Stomach’s greater curvature and gastric fundus creating a long tubular gastric conduit running along the lesser curvature.120	31.7% after 6 mo.121 BMI:44. 54±5. 45 kg/m2 to 34. 23±2. 66 after one year122		2.3 NAS score improvement.121 Falling from 5.2±1.96 to 2.63±1.55 after one year122	Significant reduction in NFS of 0.7121
	RYGB	A reconstructive procedure performed by connecting a limb of the small intestine to a small gastric pouch forming a shape of “Y.” Bypassing a portion of the large stomach pouch and proximal small intestine reduces the amount of nutrients and calories being absorbed.123	34.6% after 6 mo.121	Improvement or complete resolution of steatosis, by 91%.123	Improvement or complete resolution of steatohepatitis by 60%, y.123 -2.8 NAS score Improvement121	31% improvement in NFS123 NFS score.-1.0 reduction121

Abbreviations: NAS, nonalcoholic fatty liver disease activity score; NFS, nonalcoholic fatty liver disease fibrosis score; TBWL, total body weight loss; INS, Insulin Resistance; HS, hepatic steatosis; MED/LC, Mediterranean/low-carbohydrate; HFC, hepatic fat content; IHL, In intrahepatic lipid; LS, Liver stiffness; GHb, Glycated hemoglobin; HOMA-IR, Homeostasis model assessment; LF/HCD, low-fat, high-carb diet; GGT, gamma-glutamyl transferase; ALT, alanine aminotransferase; GLP-1, glucagon-like peptide 1; HbA1C, Hemoglobin A1c; T2DM, type 2 diabetes; LFC, Liver fat content; wk, weeks; IGB, intragastric balloon; mo, months; ESG, Endoscopic sleeve Gastroplasty; HSI, Hepatic steatosis index; DMR, endoscopic duodenal mucosal resurfacing; SG, Sleeve gastrectomy; BMI, Body mass index; RYGB, Roux-en-Y gastric Bypass; y, year.