HBV DNA integration and somatic mutations in HCC patients with HBV-HCV dual infection reveals profiles intermediate between HBV- and HCV-related HCC
Abstract Background In regions with a high prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, coinfected patients face a heightened risk of developing hepatocellular carcinoma (HCC), termed HBV/HCV-related HCC (HBCV-HCC). We aimed to investigate the contribution of...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | https://doi.org/10.1186/s12929-024-01094-7 |
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| author | Chiao-Ling Li Chia-Lang Hsu You-Yu Lin Ming-Chih Ho Rey-Heng Hu Sheng-Tai Tzeng Ya-Chun Wang Yasuhito Tanaka Pei-Jer Chen Shiou-Hwei Yeh |
| author_facet | Chiao-Ling Li Chia-Lang Hsu You-Yu Lin Ming-Chih Ho Rey-Heng Hu Sheng-Tai Tzeng Ya-Chun Wang Yasuhito Tanaka Pei-Jer Chen Shiou-Hwei Yeh |
| author_sort | Chiao-Ling Li |
| collection | DOAJ |
| description | Abstract Background In regions with a high prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, coinfected patients face a heightened risk of developing hepatocellular carcinoma (HCC), termed HBV/HCV-related HCC (HBCV-HCC). We aimed to investigate the contribution of preexisting chronic hepatitis B (CHB) and subsequent chronic hepatitis C (CHC) to the development of HBCV-HCC. Methods We examined HBV’s involvement in 93 HBCV-HCC cases by analyzing HBV DNA integration as an indicator of HCC originating from HBV-infected hepatocytes, compared with 164 HBV-HCCs and 56 HCV-HCCs as controls. Results Next generation sequencing revealed that 55% of HBCV-HCCs exhibited clonal HBV integration, which falls between the rates observed in HBV-HCCs (88%) and HCV-HCCs (7%), with similar integration patterns to HBV-HCCs. Common HCC somatic mutation analysis indicated HCV superinfection in HBCV-HCCs correlated with increased mutation rates in the telomerase reverse transcriptase (TERT) promoter and beta-catenin genes. Transcriptome analysis showed a prevalence of replicating HCV over HBV in HBCV-HCCs, with preexisting HBV exerting a proliferative role. The comparison of clinical characteristics revealed similarities between HBCV-HCC and HCV-HCC patients, including later onset for HBCV-HCC, possibly due to HCV superinfection slowing carcinogenesis. Notably, HBCV-HCCs with the same driver mutation, HBV integration at the TERT promoter, tended to develop later and showed a better prognosis post-tumor resection than HBV-HCCs. Conclusions Our findings shed light on the interplay between preexisting CHB and subsequent CHC in elevating the risk of HBCV-HCC. These insights are crucial for understanding viral etiology-specific carcinogenesis and guiding surveillance policies for HBCV-HCC post-antiviral therapy. |
| format | Article |
| id | doaj-art-1e6a1a03230a4c21aa470e89a7ab64fe |
| institution | Kabale University |
| issn | 1423-0127 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj-art-1e6a1a03230a4c21aa470e89a7ab64fe2025-01-05T12:42:29ZengBMCJournal of Biomedical Science1423-01272025-01-0132111210.1186/s12929-024-01094-7HBV DNA integration and somatic mutations in HCC patients with HBV-HCV dual infection reveals profiles intermediate between HBV- and HCV-related HCCChiao-Ling Li0Chia-Lang Hsu1You-Yu Lin2Ming-Chih Ho3Rey-Heng Hu4Sheng-Tai Tzeng5Ya-Chun Wang6Yasuhito Tanaka7Pei-Jer Chen8Shiou-Hwei Yeh9Graduate Institute of Microbiology, National Taiwan University College of MedicineDepartment of Medical Research, National Taiwan University HospitalGraduate Institute of Clinical Medicine, National Taiwan University College of MedicineDepartment of Surgery, National Taiwan University HospitalDepartment of Surgery, National Taiwan University HospitalTCM Biotech International Corp.TCM Biotech International Corp.Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto UniversityGraduate Institute of Clinical Medicine, National Taiwan University College of MedicineGraduate Institute of Microbiology, National Taiwan University College of MedicineAbstract Background In regions with a high prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, coinfected patients face a heightened risk of developing hepatocellular carcinoma (HCC), termed HBV/HCV-related HCC (HBCV-HCC). We aimed to investigate the contribution of preexisting chronic hepatitis B (CHB) and subsequent chronic hepatitis C (CHC) to the development of HBCV-HCC. Methods We examined HBV’s involvement in 93 HBCV-HCC cases by analyzing HBV DNA integration as an indicator of HCC originating from HBV-infected hepatocytes, compared with 164 HBV-HCCs and 56 HCV-HCCs as controls. Results Next generation sequencing revealed that 55% of HBCV-HCCs exhibited clonal HBV integration, which falls between the rates observed in HBV-HCCs (88%) and HCV-HCCs (7%), with similar integration patterns to HBV-HCCs. Common HCC somatic mutation analysis indicated HCV superinfection in HBCV-HCCs correlated with increased mutation rates in the telomerase reverse transcriptase (TERT) promoter and beta-catenin genes. Transcriptome analysis showed a prevalence of replicating HCV over HBV in HBCV-HCCs, with preexisting HBV exerting a proliferative role. The comparison of clinical characteristics revealed similarities between HBCV-HCC and HCV-HCC patients, including later onset for HBCV-HCC, possibly due to HCV superinfection slowing carcinogenesis. Notably, HBCV-HCCs with the same driver mutation, HBV integration at the TERT promoter, tended to develop later and showed a better prognosis post-tumor resection than HBV-HCCs. Conclusions Our findings shed light on the interplay between preexisting CHB and subsequent CHC in elevating the risk of HBCV-HCC. These insights are crucial for understanding viral etiology-specific carcinogenesis and guiding surveillance policies for HBCV-HCC post-antiviral therapy.https://doi.org/10.1186/s12929-024-01094-7Hepatocellular carcinomaHepatitis B virusHepatitis C virus |
| spellingShingle | Chiao-Ling Li Chia-Lang Hsu You-Yu Lin Ming-Chih Ho Rey-Heng Hu Sheng-Tai Tzeng Ya-Chun Wang Yasuhito Tanaka Pei-Jer Chen Shiou-Hwei Yeh HBV DNA integration and somatic mutations in HCC patients with HBV-HCV dual infection reveals profiles intermediate between HBV- and HCV-related HCC Journal of Biomedical Science Hepatocellular carcinoma Hepatitis B virus Hepatitis C virus |
| title | HBV DNA integration and somatic mutations in HCC patients with HBV-HCV dual infection reveals profiles intermediate between HBV- and HCV-related HCC |
| title_full | HBV DNA integration and somatic mutations in HCC patients with HBV-HCV dual infection reveals profiles intermediate between HBV- and HCV-related HCC |
| title_fullStr | HBV DNA integration and somatic mutations in HCC patients with HBV-HCV dual infection reveals profiles intermediate between HBV- and HCV-related HCC |
| title_full_unstemmed | HBV DNA integration and somatic mutations in HCC patients with HBV-HCV dual infection reveals profiles intermediate between HBV- and HCV-related HCC |
| title_short | HBV DNA integration and somatic mutations in HCC patients with HBV-HCV dual infection reveals profiles intermediate between HBV- and HCV-related HCC |
| title_sort | hbv dna integration and somatic mutations in hcc patients with hbv hcv dual infection reveals profiles intermediate between hbv and hcv related hcc |
| topic | Hepatocellular carcinoma Hepatitis B virus Hepatitis C virus |
| url | https://doi.org/10.1186/s12929-024-01094-7 |
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