Bridging viral hepatitis and liver cancer: Emerging concepts in pathogenesis and therapeutic innovation
Abstract Background Viral hepatitis, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, represent the predominant etiological factors for hepatocellular carcinoma (HCC) worldwide. HBV and HCV drive hepatocellular malignant transformation through complex molecular mechanisms...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-06-01
|
| Series: | Clinical and Translational Discovery |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ctd2.70063 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849683339882004480 |
|---|---|
| author | Keyin Zheng Aimin Jiang Zhengrui Li Li Chen Kailai Li Junyi Shen Hank Z. H. Wong Quan Cheng Jian Zhang Anqi Lin Peng Luo |
| author_facet | Keyin Zheng Aimin Jiang Zhengrui Li Li Chen Kailai Li Junyi Shen Hank Z. H. Wong Quan Cheng Jian Zhang Anqi Lin Peng Luo |
| author_sort | Keyin Zheng |
| collection | DOAJ |
| description | Abstract Background Viral hepatitis, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, represent the predominant etiological factors for hepatocellular carcinoma (HCC) worldwide. HBV and HCV drive hepatocellular malignant transformation through complex molecular mechanisms that are both distinct and overlapping. Comprehensive elucidation of these mechanisms, particularly the role of viral‐mediated remodeling of the tumor microenvironment, is crucial for developing novel preventive and diagnostic strategies as well as personalized therapeutic approaches. Aim This review aims to systematically elucidate the key molecular mechanisms underlying HBV‐ and HCV‐related HCC development and progression (including virus‐specific pathways and common pathways), to explore the translational potential of these mechanisms in clinical medicine, and to provide perspectives on future research frontiers. Results This review systematically elucidates the pathogenic mechanisms of HBV‐ and HCV‐related HCC and provides comprehensive analysis of the common molecular mechanisms underlying viral hepatitis‐to‐HCC transformation. For HBV‐related HCC, we focus on analyzing the following oncogenic mechanisms: genomic instability caused by HBV DNA integration, oncogenic effects of HBV proteins, and the impact of virus infection‐mediated tumor microenvironment remodeling on immune responses. For HCV‐related HCC, we focus on exploring the following oncogenic mechanisms: oncogenic mechanisms of viral proteins, virus infection‐mediated metabolic disorders, functional dysregulation of immune cells in the microenvironment, and virus‐induced hepatic fibrosis. Furthermore, we thoroughly investigated the common mechanisms underlying viral hepatitis‐to‐HCC transformation, including the construction of pro‐inflammatory factor networks in chronic inflammatory microenvironments, virus‐induced epigenetic alterations, and genomic instability. Based on current research, we further discuss future research directions and perspectives in this field. Conclusion This review systematically elucidates the pathogenic mechanisms of HBV‐ and HCV‐related HCC and provides comprehensive analysis of the common molecular mechanisms underlying viral hepatitis‐to‐HCC transformation, with particular emphasis on the remodeling effects of viral infection on the HCC microenvironment, which hold significant clinical implications for developing novel preventive strategies, diagnostic biomarkers, and personalized therapeutic approaches. Through systematic analysis of the long‐term effects of virus infection‐induced epigenetic reprogramming in HCC development and progression, combined with multi‐omics data to construct HCC risk prediction models, our findings provide scientific evidence for the development of early screening and precision treatment strategies. Meanwhile, investigating the relationship between viral integration patterns and HCC prognosis, and developing novel molecular classification methods, will facilitate the design of more individualized and precise treatment regimens for patients. Additionally, utilizing cutting‐edge artificial intelligence technologies and developing innovative research approaches such as viral hepatitis‐related liver organoid models will also provide novel insights and methodologies for reducing the incidence and mortality of viral hepatitis‐related HCC. |
| format | Article |
| id | doaj-art-5442aff6ecc942db9ce42e4a0094fb32 |
| institution | DOAJ |
| issn | 2768-0622 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Discovery |
| spelling | doaj-art-5442aff6ecc942db9ce42e4a0094fb322025-08-20T03:23:56ZengWileyClinical and Translational Discovery2768-06222025-06-0153n/an/a10.1002/ctd2.70063Bridging viral hepatitis and liver cancer: Emerging concepts in pathogenesis and therapeutic innovationKeyin Zheng0Aimin Jiang1Zhengrui Li2Li Chen3Kailai Li4Junyi Shen5Hank Z. H. Wong6Quan Cheng7Jian Zhang8Anqi Lin9Peng Luo10Department of Oncology Zhujiang Hospital, The First School of Clinical Medicine, Southern Medical University; Donghai County People's Hospital (Affiliated Kangda College of Nanjing Medical University) Lianyungang ChinaDepartment of Urology Changhai Hospital, Naval Medical University (Second Military Medical University) Shanghai ChinaDepartment of Oral and Cranio‐Maxillofacial Surgery Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology Shanghai ChinaCancer Centre and Institute of Translational Medicine, Faculty of Health Sciences University of Macau Macau SAR ChinaDepartment of Oncology Zhujiang Hospital, Southern Medical University Guangzhou Guangdong ChinaDepartment of Oncology Zhujiang Hospital, Southern Medical University Guangzhou Guangdong ChinaLi Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR ChinaDepartment of Neurosurgery Xiangya Hospital, Central South University Changsha Hunan ChinaDepartment of Oncology Zhujiang Hospital, Southern Medical University Guangzhou Guangdong ChinaDepartment of Oncology Zhujiang Hospital, The First School of Clinical Medicine, Southern Medical University; Donghai County People's Hospital (Affiliated Kangda College of Nanjing Medical University) Lianyungang ChinaDepartment of Oncology Zhujiang Hospital, The First School of Clinical Medicine, Southern Medical University; Donghai County People's Hospital (Affiliated Kangda College of Nanjing Medical University) Lianyungang ChinaAbstract Background Viral hepatitis, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, represent the predominant etiological factors for hepatocellular carcinoma (HCC) worldwide. HBV and HCV drive hepatocellular malignant transformation through complex molecular mechanisms that are both distinct and overlapping. Comprehensive elucidation of these mechanisms, particularly the role of viral‐mediated remodeling of the tumor microenvironment, is crucial for developing novel preventive and diagnostic strategies as well as personalized therapeutic approaches. Aim This review aims to systematically elucidate the key molecular mechanisms underlying HBV‐ and HCV‐related HCC development and progression (including virus‐specific pathways and common pathways), to explore the translational potential of these mechanisms in clinical medicine, and to provide perspectives on future research frontiers. Results This review systematically elucidates the pathogenic mechanisms of HBV‐ and HCV‐related HCC and provides comprehensive analysis of the common molecular mechanisms underlying viral hepatitis‐to‐HCC transformation. For HBV‐related HCC, we focus on analyzing the following oncogenic mechanisms: genomic instability caused by HBV DNA integration, oncogenic effects of HBV proteins, and the impact of virus infection‐mediated tumor microenvironment remodeling on immune responses. For HCV‐related HCC, we focus on exploring the following oncogenic mechanisms: oncogenic mechanisms of viral proteins, virus infection‐mediated metabolic disorders, functional dysregulation of immune cells in the microenvironment, and virus‐induced hepatic fibrosis. Furthermore, we thoroughly investigated the common mechanisms underlying viral hepatitis‐to‐HCC transformation, including the construction of pro‐inflammatory factor networks in chronic inflammatory microenvironments, virus‐induced epigenetic alterations, and genomic instability. Based on current research, we further discuss future research directions and perspectives in this field. Conclusion This review systematically elucidates the pathogenic mechanisms of HBV‐ and HCV‐related HCC and provides comprehensive analysis of the common molecular mechanisms underlying viral hepatitis‐to‐HCC transformation, with particular emphasis on the remodeling effects of viral infection on the HCC microenvironment, which hold significant clinical implications for developing novel preventive strategies, diagnostic biomarkers, and personalized therapeutic approaches. Through systematic analysis of the long‐term effects of virus infection‐induced epigenetic reprogramming in HCC development and progression, combined with multi‐omics data to construct HCC risk prediction models, our findings provide scientific evidence for the development of early screening and precision treatment strategies. Meanwhile, investigating the relationship between viral integration patterns and HCC prognosis, and developing novel molecular classification methods, will facilitate the design of more individualized and precise treatment regimens for patients. Additionally, utilizing cutting‐edge artificial intelligence technologies and developing innovative research approaches such as viral hepatitis‐related liver organoid models will also provide novel insights and methodologies for reducing the incidence and mortality of viral hepatitis‐related HCC.https://doi.org/10.1002/ctd2.70063Chronic viral hepatitisHepatitis BHepatitis CHepatocellular carcinoma |
| spellingShingle | Keyin Zheng Aimin Jiang Zhengrui Li Li Chen Kailai Li Junyi Shen Hank Z. H. Wong Quan Cheng Jian Zhang Anqi Lin Peng Luo Bridging viral hepatitis and liver cancer: Emerging concepts in pathogenesis and therapeutic innovation Clinical and Translational Discovery Chronic viral hepatitis Hepatitis B Hepatitis C Hepatocellular carcinoma |
| title | Bridging viral hepatitis and liver cancer: Emerging concepts in pathogenesis and therapeutic innovation |
| title_full | Bridging viral hepatitis and liver cancer: Emerging concepts in pathogenesis and therapeutic innovation |
| title_fullStr | Bridging viral hepatitis and liver cancer: Emerging concepts in pathogenesis and therapeutic innovation |
| title_full_unstemmed | Bridging viral hepatitis and liver cancer: Emerging concepts in pathogenesis and therapeutic innovation |
| title_short | Bridging viral hepatitis and liver cancer: Emerging concepts in pathogenesis and therapeutic innovation |
| title_sort | bridging viral hepatitis and liver cancer emerging concepts in pathogenesis and therapeutic innovation |
| topic | Chronic viral hepatitis Hepatitis B Hepatitis C Hepatocellular carcinoma |
| url | https://doi.org/10.1002/ctd2.70063 |
| work_keys_str_mv | AT keyinzheng bridgingviralhepatitisandlivercanceremergingconceptsinpathogenesisandtherapeuticinnovation AT aiminjiang bridgingviralhepatitisandlivercanceremergingconceptsinpathogenesisandtherapeuticinnovation AT zhengruili bridgingviralhepatitisandlivercanceremergingconceptsinpathogenesisandtherapeuticinnovation AT lichen bridgingviralhepatitisandlivercanceremergingconceptsinpathogenesisandtherapeuticinnovation AT kailaili bridgingviralhepatitisandlivercanceremergingconceptsinpathogenesisandtherapeuticinnovation AT junyishen bridgingviralhepatitisandlivercanceremergingconceptsinpathogenesisandtherapeuticinnovation AT hankzhwong bridgingviralhepatitisandlivercanceremergingconceptsinpathogenesisandtherapeuticinnovation AT quancheng bridgingviralhepatitisandlivercanceremergingconceptsinpathogenesisandtherapeuticinnovation AT jianzhang bridgingviralhepatitisandlivercanceremergingconceptsinpathogenesisandtherapeuticinnovation AT anqilin bridgingviralhepatitisandlivercanceremergingconceptsinpathogenesisandtherapeuticinnovation AT pengluo bridgingviralhepatitisandlivercanceremergingconceptsinpathogenesisandtherapeuticinnovation |