Hepatitis B virus infection - An insight into the clinical connection and molecular interaction between hepatitis B virus and host extrahepatic cancer risk

Sep 24, 2026

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Chronic hepatitis B virus (HBV) infection has well-established links to hepatocellular carcinoma, yet accumulating preclinical and observational findings indicate a comparable importance in extrahepatic cancer occurrence and survival, especially for gastrointestinal-derived cancers. This narrative review integrates evidence on immune microenvironment alterations, including immune-suppressive cytokine infiltration; epigenetic regulation such as N6-methyladenosine; signaling pathways including PI3K–Akt and Wnt; and serum biomarkers, notably HBx protein, to explain molecular mechanisms driving extrahepatic carcinogenesis and risk assessment.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

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Introduction

Epidemiology of chronic hepatitis B

TYPE Review PUBLISHED 01 March 2023 DOI 10.3389/fimmu.2023.1141956 OPEN ACCESS EDITED BY Sha Wu, Southern Medical University, China REVIEWED BY Azam Roohi, Tehran University of Medical Sciences, Iran Zhinan Yin, Jinan University, China *CORRESPONDENCE Xingchen Peng [pxx2014@163.com](pxx2014@163.com)[ ](pxx2014@163.com)Xiaolin Hu [huxiaolin@wchscu.cn](huxiaolin@wchscu.cn) †These authors have contributed equally in this work SPECIALTY SECTION This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology RECEIVED 11 January 2023 ACCEPTED 20 February 2023 PUBLISHED 01 March 2023 CITATION Min Y, Wei X, Xia X, Wei Z, Li R, Jin J, Liu Z, Hu X and Peng X (2023) Hepatitis B virus infection: An insight into the clinical connection and molecular interaction between hepatitis B virus and host extrahepatic cancer risk. Front. Immunol. 14:1141956 . doi: 10.3389/fimmu.2023.1141956 COPYRIGHT © 2023 Min, Wei, Xia, Wei, Li, Jin, Liu, Hu and Peng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Hepatitis B virus infection: An insight into the clinical connection and molecular interaction between hepatitis B virus and host extrahepatic cancer risk Yu Min 1†, Xiaoyuan Wei 2†, Xi Xia 3, Zhigong Wei 1, Ruidan Li 1, Jing Jin 1, Zheran Liu 1, Xiaolin Hu 4* and Xingchen Peng 1* 1 Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Sichuan, China, 2 Department of Head and Neck Oncology, Department of Radiation Oncology, Cancer Center, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, China, 3 Research and Development Department Shanghai ETERN Biopharma Co., Ltd., Shanghai, China, 4West China School of Nursing, West China Hospital, Sichuan University, Sichuan, China The evidence for chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence is well established. The hepatocyte epithelium carcinogenesis caused by HBV has been investigated and reviewed in depth. Nevertheless, recent ﬁndings from preclinical and observational studies suggested that chronic HBV infection is equally important in extrahepatic cancer occurrence and survival, speciﬁcally gastrointestinal system-derived cancers. Immune microenvironment changes (immune-suppressive cytokine inﬁltration), epigenetic modiﬁcation (N6-methyladenosine), molecular signaling pathways (PI3K–Akt and Wnt), and serum biomarkers such as hepatitis B virus X (HBx) protein are potential underlying mechanisms in chronic HBV infectioninduced extrahepatic cancers. This narrative review aimed to comprehensively summarize the most recent advances in evaluating the association between chronic HBV infection and extrahepatic cancer risk and explore the potential underlying molecular mechanisms in the carcinogenes is induction of extrahepatic cancers in chronic HBV conditions. KEYWORDS hepatitis B virus, extrahepatic cancer, immune microenvironment, risk factor, molecular mechanisms 1 Introduction Hepatitis B (HBV) infection is one of the leading global public health issues to date. There are approximately 316 million hepatitis B surface antigen (HBsAg)-seropositive carriers, speciﬁcally in the developing and poor countries (1, 2) . The serum indicators, which include HBsAg, hepatitis B core antigen (HBcAg), hepatitis B e antigen (HBeAg), Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) hepatitis B virus X (HBx) protein, and HBV DNA copies, are cruc

FAQs

What is the main clinical link discussed between chronic HBV and cancer?

Chronic HBV infection is discussed as an important contributor not only to hepatocellular carcinoma, but also to extrahepatic cancer occurrence and survival, with particular emphasis on cancers derived from the gastrointestinal system.

Which underlying mechanisms are proposed for HBV-related extrahepatic cancers?

The review highlights immune microenvironment changes (including immune-suppressive cytokine infiltration), epigenetic modification such as N6-methyladenosine, molecular signaling pathways (PI3K–Akt and Wnt), and serum biomarkers including the HBx protein.

How do epidemiological findings support HBV-associated extrahepatic cancer risk?

Evidence cited includes reports and studies showing that HBV seropositivity is associated with increased risks for multiple extrahepatic cancers, along with population-based and meta-analytic findings that quantify these previously underestimated connections.

Sep 24, 2026

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