Research Spotlight: association of statin, metformin, and aspirin use with hepatocellular carcinoma in the all of us research program

Erik Almazan, MD, of the Department of Medicine at Brigham and Women’s Hospital and Raymond T. Chung, MD,  of the Liver Center at Massachusetts General Hospital, are the authors of a paper published in Gastro Hep Advances [https://www.sciencedirect.com/science/article/pii/S2772572324001298] .

How would you summarize your study for a lay audience?

Hepatocellular carcinoma (HCC), the most common type of liver cancer in adults, has a very poor prognosis and is increasing at an alarming rate across the globe. In other parts of the world, chronic hepatitis C and hepatitis B are the major contributors to HCC burden.

In the U.S., however, alcohol-associated liver disease and metabolic syndrome are also major contributors. Many people with metabolic syndrome are prescribed statins, aspirin, and/or metformin for the management of comorbid conditions. These medications are relatively inexpensive and prior data has shown that they could potentially reduce the risk of HCC. We studied data from the All of Us Research Program to learn more about the protective effects of statins, and found that certain types reduced the risk of HCC, while others had no protective effects.

What question were you investigating?

We wanted to investigate the effects of statin-exposure on the risk of HCC.

What methods or approach did you use?

We used data collected through the All of Us Research Program, a national precision-medicine initiative sponsored by the NIH, to investigate the odds of HCC in participants with liver fibrosis (scarring) or cirrhosis based on their exposure to statins, aspirin, and metformin.

We also examined the odds of HCC based on exposure to specific statin subtypes, namely hydrophilic or lipophilic statins, the latter of which have been specifically associated with reduced HCC odds.

What did you find?

We found that lipophilic statins (such as atorvastatin or simvastatin) were associated with lower odds of HCC. Hydrophilic statins (such as pravastatin or rosuvastatin), as well as aspirin and metformin were not associated with decreased odds of HCC, however.

What are the implications?

The use of lipophilic statins may be an effective strategy for chemoprevention in HCC. Patients with indications for statin use and risk factors for HCC may benefit from selection of a lipophilic statin compared to a hydrophilic statin. Further prospective study of this association is warranted.

What are the next steps?

A multi-center clinical trial, NCT05028829, evaluating the use of atorvastatin, a lipophilic statin, and HCC is ongoing to determine whether the risk of HCC can be reduced in patients at high risk. We also hope to continue working with the All of Us Research Program to evaluate the role of statins in liver fibrosis progression, an important precursor to HCC.

Authorship:

Erik Almazan, MD and Raymond T. Chung, MD.

Paper cited:

Almazan E, Chung RT, Association of Statin, Metformin, and Aspirin Use with Hepatocellular Carcinoma in the All of Us Research Program, Gastro Hep Advances (2024), doi: https:// doi.org/10.1016/j.gastha.2024.08.014.

Funding:

The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Journal Pre-proofHealth Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276.*  NIH R01 CA255621, U01 CA288375 

Disclosures:

The authors do not have any disclosures.