Do Weight Loss Medications Reduce the Risk of Cirrhosis and HCC?

Introduction: Obesity is a risk factor for Nonalcoholic Fatty Liver Disease (NAFLD). NAFLD has an increased risk of development of cirrhosis and hepatocellular carcinoma (HCC). Weight loss medications have been used to treat NAFLD. However, there is limited data showing whether these medications reduce the risk of cirrhosis and HCC. Our aim is to determine whether there is a correlation between weight loss medications and the development of cirrhosis and HCC in an obese population. Methods: We performed a retrospective analysis in the IBM Explorys database 5 (1999-2021), a pooled, national, de-identified clinical database of over 72 million unique patients from 26 health care networks and 300 hospitals across the United States. Patient populations were identified using SNOMED and ICD codes. Obese patients (BMI greater than 30) started on weight loss medications including Orlistat, Phentermine/Topiramate, Lorcaserin, Bupropion/Naltrexone, or Liraglutide were identified. Patient data was evaluated to determine the number of patients who had developed cirrhosis or HCC, after at least 3 months of medication. Patient data was analyzed for complications of cirrhosis, including development of ascites, esophageal varices (EV), and hepatic encephalopathy. Odds ratio with 95% CI were calculated to assess risk of cirrhosis, cirrhosis complications, and HCC compared to a control cohort. Results: Weight loss medications reduced the risk of development of HCC (OR 0.07, CI 0.06-0.08) in obese populations. When medications were analyzed individually for risk of HCC, Orlistat and Liraglutide showed a statistically significant decreased risk (OR 0.13, CI 0.08-0.20 and OR 0.35, CI 0.29-0.41, respectively).Use of weight loss medications was associated with a reduced risk of cirrhosis and associated complications in obese patients. Phentermine/Topiramate, Lorcaserin, and Bupropion/Naltrexone had statistically significant reduction in cirrhosis (OR 0.41, CI 0.34-0.49; OR 0.44, CI 0.37-0.52; OR 0.33, CI 0.28-0.39, respectively). Orlistat, Liraglutide, and Bupropion/Naltrexone had reductions in EV. Orlistat, Liraglutide, Phentermine/Topiramate had reduced risk of HE. Conclusion: Obesity is a major risk factor for NAFLD. Our results suggest that weight loss medications reduce the risk of HCC, cirrhosis, and cirrhosis complications. Clinicians should consider weight loss medications for patients who are unable to lose weight through lifestyle modifications. Future prospective studies are needed to validate these studies.Figure 1.: Odds ratio for weight loss medications and the development of cirrhosis in an obese population.