乙型肝炎病毒通过调节对环境致癌物的免疫反应来促进肝癌。

Hepatitis B virus promotes liver cancer by modulating the immune response to environmental carcinogens.

作者信息

Huang Mei, Wang Dongyao, Huang Jiao, Bae An-Na, Xia Yun, Zhao Xutu, Mortaja Mahsa, Azin Marjan, Collier Michael R, Semenov Yevgeniy R, Park Jong Ho, Demehri Shadmehr

机构信息

Center for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

出版信息

Nat Commun. 2025 Jun 27;16(1):5360. doi: 10.1038/s41467-025-60894-z.

DOI:10.1038/s41467-025-60894-z

PMID:40579434

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12205058/

Abstract

Hepatitis B virus (HBV) infection is associated with hepatitis and hepatocellular carcinoma (HCC). Considering that most HBV-infected individuals remain asymptomatic, the mechanism linking HBV to hepatitis and HCC remains uncertain. Herein, we demonstrate that HBV alone does not cause liver inflammation or cancer. Instead, HBV alters the chronic inflammation induced by chemical carcinogens to promote liver carcinogenesis. Long-term HBV genome expression in mouse liver increases liver inflammation and cancer propensity caused by a carcinogen, diethylnitrosamine (DEN). HBV plus DEN-activated interleukin-33 (IL-33)/regulatory T cell axis is required for liver carcinogenesis. Pitavastatin, an IL-33 inhibitor, suppresses HBV plus DEN-induced liver cancer. IL-33 is markedly elevated in HBV hepatitis patients, and pitavastatin use significantly correlates with reduced risk of hepatitis and its associated HCC in patients. Collectively, our findings reveal that environmental carcinogens are the link between HBV and HCC risk, creating a window of opportunity for cancer prevention in HBV carriers.

摘要

乙型肝炎病毒（HBV）感染与肝炎及肝细胞癌（HCC）相关。鉴于大多数HBV感染者无症状，HBV与肝炎及HCC之间的联系机制仍不明确。在此，我们证明单独的HBV不会引发肝脏炎症或癌症。相反，HBV会改变化学致癌物诱导的慢性炎症，以促进肝癌发生。在小鼠肝脏中长期表达HBV基因组会增加由致癌物二乙基亚硝胺（DEN）引起的肝脏炎症和癌症倾向。肝脏致癌需要HBV加DEN激活的白细胞介素-33（IL-33）/调节性T细胞轴。匹伐他汀作为一种IL-33抑制剂，可抑制HBV加DEN诱导的肝癌。IL-33在HBV肝炎患者中显著升高，使用匹伐他汀与降低患者肝炎及其相关HCC的风险显著相关。总体而言，我们的研究结果表明环境致癌物是HBV与HCC风险之间的联系，为HBV携带者预防癌症创造了机会之窗。