Hepatitis B virus (HBV) infection is known to be associated with an increased risk of hepatocellular carcinoma (HCC), but the mechanism by which 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 induced 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 to 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 was significantly reduced in patients treated with a statin compared with those treated with another cholesterol-lowering drug.
Source: Massachusetts General Hospital
Paper: 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
