Study identifies ways to lower risk of liver cancer for people with hepatitis B infection

Hepatitis B virus (HBV) infection is known to be associated with the risk of hepatocellular carcinoma (HCC), but how and why they are connected remains unknown. Researchers from Mass General Brigham discovered that HBV does not cause liver inflammation or cancer on its own, but worsens liver inflammation and may make patients more susceptible to early cancer development caused by environmental carcinogens. Limiting carcinogen exposure or reducing inflammation could mitigate this risk. The results are published in Nature Communications. 

“Our research sheds light on the intricate interplay between HBV infection and carcinogen exposure to generate immune dysregulation in the liver that leads to cancer development,” said corresponding author Shawn Demehri, MD, PhD, of the Demehri Lab and Krantz Family Center for Cancer Research at Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system. “We propose the potential of combining statin therapy with conventional HBV treatments like entecavir to improve patient outcomes.”  

Using a mouse model, the researchers found that HBV did not directly cause liver inflammation or cancer. However, when the HBV models were exposed to a carcinogen found in tobacco smoke, fried foods, processed meats, and alcoholic drinks, they developed an extreme liver cancer phenotype. This carcinogen, also known as diethylnitrosamine (DEN), caused an increase in interleukin-33 (IL-33), an inflammatory molecule, which is required for the development of liver cancer. The researchers then treated the models with pitavastatin, a statin drug, to suppress the expression of IL-33. This treatment was effective in reducing the risk of chronic hepatitis and liver cancer.  

The researchers then extended their findings into humans, finding higher levels of IL-33, especially in patients with HBV-associated hepatitis, compared to healthy controls. They then looked at data from more than 200 million patients, finding that the risk of hepatitis and liver cancer were significantly reduced in patients treated with a statin compared with those treated with another cholesterol-lowering drug.  

Authorship: In addition to Demehri, Mass General Brigham authors include Mei Huang, Dongyao Wang, Jiao Huang, Yun Xia, Xutu Zhao, Mahsa Mortaja, Marjan Azin, Michael R. Collier, Yevgeniy R. Semenov, and Jong Ho Park. Additional authors include An-Na Bae.  

Funding: This study was funded in part by the Burroughs Wellcome Fund (Career Award for Medical Scientists and additional grants), the National Research Foundation of Korea (RS-2024-00343783), the Natural Science Foundation of Anhui, China (2008085MH253 and 2308085Y46), the National Natural Science Foundation of China (82473312 and 82370217), and the NIH (R01CA283214). 

Disclosures: Park and Demehri are coinventors on a filed patent for the use of IL-33 inhibition in the treatment of cancer, fibrosis, and inflammation (PCT/US21/40725). All other authors declare no competing interests. 

Paper cited: Huang M et al. “Hepatitis B virus promotes liver cancer by modulating the immune response to environmental carcinogens” Nature Communications DOI: 10.1038/s41467-025-60894-z  

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Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.