517 Background: Hepatocellular carcinoma (HCC) is a major cause of cancer related morbidity and mortality worldwide, with increased incidence in patients with chronic liver disease, obesity and metabolic syndrome. Of note, increasing burden of metabolic dysfunction-associated steatohepatitis (MASH) and non-alcoholic fatty livery disease (NAFLD) has contributed to increased incidence of cirrhosis and progression to HCC. Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of type 2 diabetes and obesity. Their pleotropic benefits including improved insulin sensitivity, potential anti-proliferative and anti-inflammatory benefits may significantly benefit these patients by potentially reduced hepatic inflammation and steatosis. Our study aims to evaluate the impact of GLP-1 receptor agonists on outcomes among patients with hepatocellular carcinoma with comorbid obesity, exploring potential interactions between metabolic modulation and disease behaviour. Methods: A retrospective cohort study was conducted using the US Collaborative Network TriNetX, covering January 2000 to December 2023, encompassing data from 105 global healthcare organizations. Adult patients aged 18 and above with HCC and comorbid obesity were identified and then stratified into two groups based on treatment with GLP-1 agonists or not. The two groups were then propensity-matched based on age, sex, race, and common comorbidities. We followed these patients for 5 years to assess outcomes, including overall mortality, myocardial infarction, acute pancreatitis, sepsis, need for mechanical ventilation and hemodialysis. Results: We identified 401 patients with HCC and obesity who received GLP-1 receptor agonists, and 3974 patients with HCC and obesity who did not receive GLP-1 therapy. The average age was 63.7 years in the first cohort and 61.4 years in the second cohort. After propensity matching, each cohort consisted of 399 patients with similar baseline characteristics and ethnicity distribution. Our analysis found that over 5 years, patients with HCC and obesity who received GLP-1 receptor agonists had a significantly lower risk of overall mortality (Hazard Ratio (HR): 0.48, 95% CI: 0.371 to 0.623, p-value = 0.001). There was no statistically significant difference in the risk for myocardial infarction, acute pancreatitis, sepsis, need for mechanical ventilation and hemodialysis between the two subgroups. Conclusions: Our study revealed that patients with HCC and obesity who received GLP-1 receptor agonists had a significantly lower risk of mortality. Further longitudinal cohort studies are imperative to better understand these associations and guide evidence-based clinical practice in this population.
Syal et al. (Sat,) studied this question.