Study: Bile Acid Supplement Shows Promise for Liver Cancer

New study findings announced that boosting levels of ursodeoxycholic acid (UDCA) through dietary supplementation could control tumor growth for liver cancer, offering an expanded target for improving liver cancer treatment and immunotherapy.¹

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The American Cancer Society estimates that about 42,240 new cases of liver cancer and intrahepatic bile duct cancer will be diagnosed in the US in 2025, which could account for around 30,090 deaths. The incidence rates of liver cancer have tripled since 1980, and death rates have doubled in the last 40 years.²

Immunotherapy, a modern cancer treatment approach that uses an individual’s own immune system to seek and destroy cancer cells, has been used to treat individuals with liver cancer; however, it has demonstrated greater success in lung, kidney, and bladder cancers. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors such as ipilimumab (Yervoy; Bristol-Myers Squibb) and tremelimumab (Imjudo; AstraZeneca) are often used as liver cancer immunotherapies that block CTLA-4, another protein on T cells, and boost the immune response.^1,3

Scientists from the Salk Institute for Biological Studies aimed to investigate how immunotherapies could be less effective treating liver cancer compared to other cancers, looking at how the immune system and liver interact. The researchers evaluated a mouse model and human liver tumors to conduct the assessment.¹

The researchers identified elevated levels of conjugated bile acids in human liver cancer biopsies and demonstrated that inhibiting the protein BAAT, responsible for producing these bile acids, reduced tumor growth in mice, suggesting that targeting BAAT may enhance immunotherapy response in liver cancer patients.¹

Bile acids are produced in the liver from cholesterol and play an essential role in fat digestion.⁴ However, the study authors noted that for T cells to fight liver cancer, they must function around the bile acids. Excess bile acid has been associated with poor health and can worsen cancer, but previous studies lacked to identify their specific role in cancer.¹

“Livers have a particularly unique environment, but we didn’t really understand how it was affecting the immune and cancer cells. By investigating these liver-specific features, we have identified several potential ways to regulate bile acids, improve T cell performance, and enhance patient outcomes,” said Susan Kaech, PhD, senior author of the study and director of Salk’s NOMIS Center for Immunobiology and Microbial Pathogenesis, in a news release.¹

The researchers then analyzed 20 different bile acids, finding that while primary bile acids had minimal impact, UDCA had a positive effect on T cell activity in the liver. Additionally, boosting UDCA levels through dietary supplementation was able to control tumor growth in mice with liver cancer.¹

“Considering how T cell performance varies across different organs, tissues, and tumors puts us at a great vantage point for looking at ways to optimize cancer treatment,” said Siva Karthik Varanasi, former postdoctoral researcher in Kaech’s lab and current assistant professor at the University of Massachusetts Chan Medical School, in a news release. “By taking this unique approach, we’re able to see that bile acids in the liver are hugely influencing T cells’ ability to do their job and therefore may be a useful therapeutic target.”¹

UDCA supplementation is recommended for patients with cystic fibrosis with associated liver disease; however, the study authors noted that they are hopeful for its indication to treat liver cancer.^1,5

“We’re already a huge step ahead when it comes to translating our findings to the clinic, because UDCA supplementation is already used to treat liver disease and could easily be tested in liver cancer next,” said Kaech in a news release. “We are really excited to also explore the role of the gut microbiome in all of this, since bile acids are a huge part of that picture—how can we manipulate ‘good’ and ‘bad’ bacteria in the microbiome to further regulate bile acid levels? How does the microbiome change during liver cancer? Could probiotics be a therapeutic approach?”¹

REFERENCES

1. Bile acids exacerbate liver cancer; dietary supplements may offer relief. EurekAlert!. News release. January 14, 2025. Accessed January 24, 2025. https://www.eurekalert.org/news-releases/1070469

2. Key Statistics About Liver Cancer. American Cancer Society. News release. January 16, 2025. Accessed January 24, 2025. https://www.cancer.org/cancer/types/liver-cancer/about/what-is-key-statistics.html

3. Immunotherapy for liver cancer. American Cancer Society. News release. September 19, 2024. Accessed January 24, 2025. https://www.cancer.org/cancer/types/liver-cancer/treating/immunotherapy.html#:~:text=Tremelimumab%20(Imjudo)%20can%20be%20used,3%20weeks%20for%204%20treatments

4. The Continuing Importance of Bile Acids in Liver and Intestinal Disease. JAMA Internal Medicine. News release. December 27, 1999. Accessed January 24, 2025. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/1105662#:~:text=Five%20major%20physiological%20functions%20of,severe%20hepatic%20or%20systemic%20disease

5. Supplementation of ursodeoxycholic acid improves fat digestion and absorption in cystic fibrosis patients with mild liver involvement. Eur J Gastroenterol Hepatol. News release. June 28, 2016. Accessed January 24, 2025. https://journals.lww.com/eurojgh/abstract/2016/06000/supplementation_of_ursodeoxycholic_acid_improves.6.aspx