The rising mortality rate among patients with metabolic dysfunction-associated fatty liver disease (MAFLD) underscores the need for effective interventions. At the 2024 AASLD Annual Meeting, Dr. Leith Ghani from the University of Arizona College of Medicine presented a multicenter retrospective study comparing 5-year mortality rates in MAFLD patients undergoing weight-loss surgery versus those treated with glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), or a combination of these therapies. Findings indicate that weight-loss surgery outperforms pharmacologic treatments in improving survival, offering crucial insights for clinical decision-making in MAFLD management.This multicenter retrospective study, conducted within the Banner Health System, included MAFLD patients identified via ICD codes who met at least one of five metabolic criteria. Eligible participants had undergone at least one of the following interventions: weight-loss surgery, GLP-1 RA, SGLT2i, or combination therapy, with a minimum follow-up period of 12 months. The primary outcome was the 5-year mortality rate post-intervention.
To determine mortality, deaths occurring between 12 and 60 months post-intervention were recorded. Medication use was verified, and weight-loss surgeries were identified and categorized using ICD codes. A Cox regression model, adjusted for variables such as smoking status, age, BMI, gender, race, hypertension, hyperlipidemia, and diabetes, was used to compare mortality rates. Kaplan-Meier survival curves were plotted to visualize survival differences.
Key Findings
The study cohort included 8,619 patients:
- Intervention Breakdown: 5.8% underwent weight-loss surgery, 39.3% were treated with GLP-1 RA, 23.4% with SGLT2i, and 31.5% with combination therapy.
- Mortality Risk: After adjustments, the hazard ratios (aHR) for 5-year mortality compared to the weight-loss surgery group were: GLP-1 RA: aHR = 2.99 (P<0.001) SGLT2i: aHR = 2.96 (P<0.001) Combination therapy: aHR = 1.78 (P<0.001)
- Kaplan-Meier Survival: Weight-loss surgery patients demonstrated higher survival rates than those receiving GLP-1 RA, SGLT2i, or combination therapies.
This study highlights the superiority of weight-loss surgery over pharmacologic treatments in reducing 5-year mortality among MAFLD patients. Patients treated with GLP-1 RA or SGLT2i exhibited higher mortality risks, potentially due to underlying metabolic or cardiovascular conditions.
Expert Insights: Dr. Leith Ghani
Dr. Ghani emphasized that while further research is necessary, these findings have important implications for clinical practice:
- Optimizing Clinical Decisions: Physicians can use these insights to engage patients in informed discussions about the relative benefits and risks of weight-loss surgery versus pharmacologic treatments. For patients with severe metabolic or cardiovascular risks, weight-loss surgery should be considered early in the treatment process when clinically appropriate.
- Encouraging Prospective Research: These results call for randomized controlled trials to establish causality and refine clinical guidelines.
- Fostering Multidisciplinary Collaboration: The study underscores the need for integrated care involving hepatologists, endocrinologists, cardiologists, and bariatric surgeons to address the complex needs of MAFLD patients.
Future Directions
As this study marks a significant step in understanding treatment efficacy for MAFLD, it also raises questions about the underlying mechanisms driving the observed differences in mortality. Long-term, prospective studies are essential to confirm these findings and guide the development of comprehensive, personalized management strategies for MAFLD patients.
