Evidence map›Paper›PMID 40042791›Full record

ArticleDiscover oncology2025

The causal relationship between hepatitis B, immunophenotypes and liver cancer: a Mendelian randomization study.

Zhili Cao, Chunyu Zhang, Shan Chen, Jie Jiang, Xuejiao Bai, Yan Wang, Wenshuang Zhang

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Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Zhili Cao *Department of Infectious Disease, Hebei North University Affiliated Second Hospital, Zhangjiakou, 075100, Hebei, China. efyczl789@163.com.
Chunyu Zhang *Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, Chonngqing, 400010, China.
Shan ChenDepartment of Infectious Disease, Hebei North University Affiliated Second Hospital, Zhangjiakou, 075100, Hebei, China.
Jie JiangDepartment of Infectious Disease, Hebei North University Affiliated Second Hospital, Zhangjiakou, 075100, Hebei, China.
Xuejiao BaiDepartment of Infectious Disease, Hebei North University Affiliated Second Hospital, Zhangjiakou, 075100, Hebei, China.
Yan WangDepartment of Infectious Disease, Hebei North University Affiliated Second Hospital, Zhangjiakou, 075100, Hebei, China.
Wenshuang ZhangDepartment of Infectious Disease, Hebei North University Affiliated Second Hospital, Zhangjiakou, 075100, Hebei, China.

Funding

Zhangjiakou Science and Technology Plan Project 2021095D
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally, and infection with the hepatitis B virus (HBV) is one of the major risk factors for the development of HCC. However, the definitive causal relationship between HBV infection and liver cancer has not been clearly established. In this study, we employed Mendelian randomization (MR) to estimate the causal effect of HBV infection on hepatocellular carcinoma by using genetic variations as instrumental variables.

methodsWe obtained summary statistics from genome-wide association studies (GWAS) related to hepatocellular carcinoma and hepatitis B. We conducted Mendelian randomization analysis, using genetic variants associated with HBV infection as instrumental variables to estimate the risk of liver cancer. In our MR analysis, we employed the inverse variance weighted (IVW) method and performed sensitivity analyses and robustness assessments using MR Egger regression and the weighted median method.

resultsOur MR analysis revealed a significant causal association, indicating that HBV infection leads to liver cancer (IVW odds ratio = 2.233, 95% confidence interval = 1.844-2.703, P < 0.001). Sensitivity analyses using MR Egger regression and the weighted median method confirmed the causal effect, with no evidence of horizontal pleiotropy. Similar results were observed across different MR methods, supporting a strong causal association between HBV and liver cancer risk. Specifically, we observed a causal effect of CD25 on the IgD-CD38- B cell subset (β = 1.15, 95% CI 1.07-1.24, P = 3.0 × 10^- 4). Additionally, five immune phenotypes were significantly associated with HCC risk: HLA DR +  + monocytes.

conclusionThis MR study demonstrates a causal relationship between HBV infection and liver cancer risk, highlighting HBV as a potential causal factor in the development of hepatocellular carcinoma.

Indexed as

Causal relationshipHepatitis BLiver cancerMendelian randomization

Identifiers

PMID40042791
PMCPMC11883044

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.