Colton Jones, MD, on GLP-1 RAs for the Prevention of HCC in High-Risk Individuals

Hepatocellular carcinoma is a major cause of cancer related morbidity and mortality. Currently, there are no FDA approved medications for risk reduction or primary prevention of hepatocellular carcinoma. There has been a lot of evidence regarding reduction in hepatocellular carcinoma with GLP-1 agonist, particularly in patients with type 2 diabetes and in patients with metabolic associated steatotic liver disease. However, to date, there is no study that's been conducted for risk reduction of hepatocellular carcinoma in patients who have other etiologies such as alcohol, liver cirrhosis and viral hepatitis along with hereditary liver disease. This is where our study comes into play and it fills a significant gap in the medical literature. We used the TriNetX database, which is a large commercial database encompassing over 150 million participants across 112 healthcare organizations. We identified participants who were on a GLP-1 medication for more than two months and we compared it to those who are not on a GLP-1, specifically focusing on high risk participants. And we defined high risk as those participants with a history of liver cirrhosis, chronic viral hepatitis or any other hereditary related liver disease in addition to those with obesity and type 2 diabetes. At a median follow up of 2400 plus days for GLP users and 2114 days for non users, what our study found was there was an association of a 73% risk reduction in incident hepatocellular carcinoma. This risk reduction was even greater in nondiabetics and in those with a lean BMI. This was associated with an almost 80% risk reduction. In addition, there was a risk reduction in the other related groups including alcoholic cirrhosis, viral hepatitis and in those with hereditary liver conditions. We assess safety outcomes in the study and particularly we looked at gastrointestinal adverse events. GLP users were associated with a higher risk of nausea and vomiting as well as diarrhea and a lower incidence of pancreatitis and acute kidney injury. Gastrointestinal adverse events are known side effects of GLP-1 users. So in summary, our study found that there was almost a 73% risk reduction in incident hepatocellular carcinoma for GLP users and this was significant throughout all subgroups. These findings, though hypothesis-generating, require prospective validation as they may implicate a public health impact.