Causal Mediation Analyses for the Natural Course of Hepatitis C: A Prospective Cohort Study
Background: Hepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensi...
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| Format: | Article |
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Japan Epidemiological Association
2025-01-01
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| Series: | Journal of Epidemiology |
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| Online Access: | https://www.jstage.jst.go.jp/article/jea/35/1/35_JE20240034/_pdf |
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| author | Yi-Ting Huang Yao-Chun Hsu Hwai-I Yang Mei-Hsuan Lee Tai-Hsuan Lai Chien-Jen Chen Yen-Tsung Huang |
| author_facet | Yi-Ting Huang Yao-Chun Hsu Hwai-I Yang Mei-Hsuan Lee Tai-Hsuan Lai Chien-Jen Chen Yen-Tsung Huang |
| author_sort | Yi-Ting Huang |
| collection | DOAJ |
| description | Background: Hepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensively quantified the extent to which intrahepatic and extrahepatic diseases mediate HCV-induced mortality. Methods: A community-based cohort study with >25 years of follow-up was conducted in Taiwan. HCV infection was profiled by antibodies against HCV and HCV RNA in participants’ serum samples. The cohort data were linked to Taiwan’s National Health Insurance Research Database to determine the incidences of potential mediating diseases and mortality. We employed causal mediation analyses to estimate the mediation effects of HCV on mortality in relation to the incidences of 34 candidate diseases. Results: In 18,972 participants with 934 HCV infection, we observed that 54.1% of HCV-induced mortality was mediated by intrahepatic diseases, such as liver cirrhosis and liver cancer, and 45.9% of mortality was mediated by extrahepatic diseases. The major extrahepatic mediating diseases included septicemia (estimated proportion of HCV-induced mortality mediated through the disease: 25.2%), renal disease (16.7%), blood/immune diseases (12.2%), gallbladder diseases (9.7%), and endocrine diseases (9.6%). In women, hypertension (20.0%), metabolic syndrome (18.9%), and type 2 diabetes (17.0%) also mediated HCV-induced mortality. A dose-response relationship of HCV viral load was further demonstrated for the mediation effect. Conclusion: Both intrahepatic and extrahepatic manifestations mediated approximately half of HCV-induced mortality. The mediation mechanisms are supported by a dose-response relationship of HCV viral load. |
| format | Article |
| id | doaj-art-939d12fbb1064b7492f3d97baee7e890 |
| institution | Kabale University |
| issn | 0917-5040 1349-9092 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Japan Epidemiological Association |
| record_format | Article |
| series | Journal of Epidemiology |
| spelling | doaj-art-939d12fbb1064b7492f3d97baee7e8902025-01-06T03:54:45ZengJapan Epidemiological AssociationJournal of Epidemiology0917-50401349-90922025-01-01351212910.2188/jea.JE20240034Causal Mediation Analyses for the Natural Course of Hepatitis C: A Prospective Cohort StudyYi-Ting Huang0Yao-Chun Hsu1Hwai-I Yang2Mei-Hsuan Lee3Tai-Hsuan Lai4Chien-Jen Chen5Yen-Tsung Huang6Institute of Statistical Science, Academia Sinica, Taipei, TaiwanCenter for Liver Diseases, E-Da Hospital, Kaohsiung, TaiwanGenomics Research Center, Academia Sinica, Taipei, TaiwanInstitute of Clinical Medicine, Yangming Campus, National Yang Ming Chiao Tung University, Taipei, TaiwanDivision of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanGenomics Research Center, Academia Sinica, Taipei, TaiwanInstitute of Statistical Science, Academia Sinica, Taipei, TaiwanBackground: Hepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensively quantified the extent to which intrahepatic and extrahepatic diseases mediate HCV-induced mortality. Methods: A community-based cohort study with >25 years of follow-up was conducted in Taiwan. HCV infection was profiled by antibodies against HCV and HCV RNA in participants’ serum samples. The cohort data were linked to Taiwan’s National Health Insurance Research Database to determine the incidences of potential mediating diseases and mortality. We employed causal mediation analyses to estimate the mediation effects of HCV on mortality in relation to the incidences of 34 candidate diseases. Results: In 18,972 participants with 934 HCV infection, we observed that 54.1% of HCV-induced mortality was mediated by intrahepatic diseases, such as liver cirrhosis and liver cancer, and 45.9% of mortality was mediated by extrahepatic diseases. The major extrahepatic mediating diseases included septicemia (estimated proportion of HCV-induced mortality mediated through the disease: 25.2%), renal disease (16.7%), blood/immune diseases (12.2%), gallbladder diseases (9.7%), and endocrine diseases (9.6%). In women, hypertension (20.0%), metabolic syndrome (18.9%), and type 2 diabetes (17.0%) also mediated HCV-induced mortality. A dose-response relationship of HCV viral load was further demonstrated for the mediation effect. Conclusion: Both intrahepatic and extrahepatic manifestations mediated approximately half of HCV-induced mortality. The mediation mechanisms are supported by a dose-response relationship of HCV viral load.https://www.jstage.jst.go.jp/article/jea/35/1/35_JE20240034/_pdfcohort studydisease burdenmediation analysisnatural historyhepatitis c |
| spellingShingle | Yi-Ting Huang Yao-Chun Hsu Hwai-I Yang Mei-Hsuan Lee Tai-Hsuan Lai Chien-Jen Chen Yen-Tsung Huang Causal Mediation Analyses for the Natural Course of Hepatitis C: A Prospective Cohort Study Journal of Epidemiology cohort study disease burden mediation analysis natural history hepatitis c |
| title | Causal Mediation Analyses for the Natural Course of Hepatitis C: A Prospective Cohort Study |
| title_full | Causal Mediation Analyses for the Natural Course of Hepatitis C: A Prospective Cohort Study |
| title_fullStr | Causal Mediation Analyses for the Natural Course of Hepatitis C: A Prospective Cohort Study |
| title_full_unstemmed | Causal Mediation Analyses for the Natural Course of Hepatitis C: A Prospective Cohort Study |
| title_short | Causal Mediation Analyses for the Natural Course of Hepatitis C: A Prospective Cohort Study |
| title_sort | causal mediation analyses for the natural course of hepatitis c a prospective cohort study |
| topic | cohort study disease burden mediation analysis natural history hepatitis c |
| url | https://www.jstage.jst.go.jp/article/jea/35/1/35_JE20240034/_pdf |
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