Treating Obesity to Address Liver Disease

Educational Objectives

The goal of this program is to improve management of liver disease through treatment of obesity. After hearing and assimilating this program, the clinician will be better able to:

1. Cite evidence for weight loss management in liver diseases.

Summary

Efficacy of endoscopic sleeve gastroplasty (ESG): Abu Dayyeh et al (2022) found ESG was effective in achieving targeted weight loss of >25% of a patient's excess body weight; 49% of patients met the target, while 77% of the patients had excess weight loss; no treatments for NAFLD are approved by the US Food and Drug Administration; ESG improves hepatic steatosis and fibrosis in patients with NAFLD

Efficacy of semaglutide: Newsome et al (2021) found that many patients, especially those receiving higher doses of semaglutide, experienced improvement and resolution of their nonalcoholic steatohepatitis, without worsening of fibrosis; these outcomes were seen in 60% of patients in the 0.4 mg semaglutide group; similar results were observed with 2.4 mg once weekly (similar to Wegovy)

Semaglutide and ESG: a retrospective analysis studied the effects of semaglutide and ESG on patients with NAFLD, using noninvasive measures, ie, hepatic steatosis index (HSI), FIB-4, and NAFLD Fibrosis Score; at 24 mo, the semaglutide group had lost ≈10% of body weight, while the ESG group had lost ≈17%; no statistical significance in FIB-4 scores was seen between groups; the HSI, which includes more parameters than FIB-4, had significantly improved in the ESG group at 12 mo; limitations — small sample size, inability to assess medication compliance, and the use of lower-dose semaglutide; conclusion — treatment with ESG may be superior to semaglutide therapy for patients with NAFLD because of the greater reduction in total body weight at different time points; as multiple options are effective, focus on risk stratification and initiation of therapy

Additional data for ESG: a meta-analysis (Hedjoudje et al [2020]) found ESG is associated with total body weight loss of 16.5% at 12 mo, with a favorable adverse effects profile

Antiobesity medications (AOM): phentermine or phentermine-topiramate combination — relatively inexpensive and effective; data suggest the phentermine-topiramate combination may produce body weight loss of 7% to 8% in 1 yr (beneficial for NAFLD); these medications are adrenergic agonists and neurostabilizers that reduce appetite and enhance resting energy expenditure; glucagon-like peptide-1 receptor agonists (GLP-1RA) — liraglutide is given as a daily injection; semaglutide is a long-acting medication recently approved for weight loss (even without diabetes mellitus [DM]); regulate insulin and glucagon secretion, inhibit gastric emptying, enhance satiety, and reduce appetite

Analysis of combination therapy: evaluated the effectiveness of ESG and AOM combination therapy (AOMs prescribed ≤6 mo before or after ESG) vs monotherapy (ESG only) vs sequential therapy (AOM ≥6 mo before or after ESG); the patients who underwent ESG and started a GLP-1RA within 6 mo of their procedure lost 24% of their body weight; the sequential therapy group lost 12% of their body weight; limitations — inability to assess medication compliance; not all patients on semaglutide received 2.4-mg dosing; conclusion — combining ESG with a GLP-1RA is superior to ESG alone; the optimal time to add an AOM was within 6 mo of ESG, and being on an AOM for >6 mo before or starting ≥6 mo after the procedure was a predictor of poor response following the procedure

Duodenal mucosal resurfacing (DMR): duodenal mucosa variation (resulting from exposure to processed sugar and insulin dysregulatory pathways) is associated with worsening of outcomes of metabolic disease-related comorbidities; Mingrone et al (2022) — conducted a safety and efficacy trial of use of a hydrothermal device (Revita) for achieving DMR; enrolled patients who had DM, with hemoglobin A_1C (HbA_1C) levels of 7.5% to 10%, and obesity in class 1 and 2 categories; improvement was seen in insulin sensitivity and HbA_1C profiles at 2 yr; the authors concluded that the modality was effective; outcomes were less statistically significant when patients in the placebo group received lifestyle counseling (this should be part of the treatment regimen)

Pulsed electric field DMR: safety and efficacy were assessed in a study at the Mayo Clinic; the primary end point is the incidence of device- or procedure-related serious adverse effects at 12 wk, and secondary end points include technical success and changes in glycemic control at 24 wk; the modality was easy to deliver (the technical success rate was 100%); only mild and moderate adverse events (eg, sore throat, transient diarrhea) were observed; at 24 wk, mean HbA_1C showed significant improvement, from a mean of 8.4% to 7.5%, with the double-energy arm showing greater improvement; patients lost ≈5% of total body weight, with a variation of ≈4%

Readings

Abu Dayyeh BK, Bazerbachi F, Vargas J, et al. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022 Aug 6;400(10350):441-451; Bergmann NC, Davies MJ, Lingvay I, et al. Semaglutide for the treatment of overweight and obesity: A review. Diabetes Obes Metab. 2023 Jan;25(1):18-35; Hajifathalian K, Mehta A, Ang B, et al. Improvement in insulin resistance and estimated hepatic steatosis and fibrosis after endoscopic sleeve gastroplasty. Gastrointest Endosc. 2021 May;93(5):1110-1118; Hedjoudje A, Abu Dayyeh BK, Cheskin LJ, et al. Efficacy and safety of endoscopic sleeve gastroplasty: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2020;18(5):1043-1053.e4. doi:10.1016/j.cgh.2019.08.022; Jirapinyo, P, Jaroenlapnopparat A, Thompson CC. Endoscopic sleeve gastroplasty with anti-obesity medications: analysis of combination therapy, optimal timing and agents. Gastroenterology. 2023; 164(6), Supplement, S-1-S-1574; Mingrone G, Baar ACG, Devière J, et al. Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: the randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial. Gut. 2022;71:254-264; Newsome PN, Buchholtz K, Cusi K, et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-1124; Perdomo CM, Cohen RV, Sumithran P, et al. Contemporary medical, device, and surgical therapies for obesity in adults. Lancet. 2023 Apr 1;401(10382):1116-1130.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Newberry was recorded at the Spring Course Best of DDW 2023, held on May 20, 2023, in New York, NY, and presented by the New York Society for Gastrointestinal Endoscopy. For information on future CME activities from this presenter, please visit nysge.org. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

GE380301

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.