Long-Term Hepatic and Extrahepatic Outcomes of Chronic Hepatitis C Patients After Sofosbuvir-Based Treatment (LONGHEAD Study)
Abstract Background/Aims Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C virus (HCV) infection. The long-term hepatic and extrahepatic outcomes of DAAs in chronic hepatitis C (CHC) patients receiving curative antivirals are elusive. Methods CHC patients were retrieved fr...
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Adis, Springer Healthcare
2025-04-01
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| Online Access: | https://doi.org/10.1007/s40121-025-01145-y |
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| author | Chung-Feng Huang Jeong Heo Rong-Nan Chien Yang-Hyun Baek Jia-Horng Kao Ju-Hyun Kim Ting-Tsung Chang Kwan-Soo Byun Jyh-Jou Chen Sook-Hyang Jeong Tsung-Hui Hu Young-Seok Kim Cheng-Yuan Peng Won-Young Tak Horng-Yuan Wang Seung-Kew Yoon I.-Shyan Sheen Youn-Jae Lee Yu-Chun Hsu Hyung-Joon Yim Pei-Chien Tsai Ming-Lun Yeh Sang-Hoon Ahn Chia-Yen Dai Seung-Woon Paik Jee-Fu Huang Yoon-Jun Kim Wan-Long Chuang Young-Suk Lim Ming-Lung Yu |
| author_facet | Chung-Feng Huang Jeong Heo Rong-Nan Chien Yang-Hyun Baek Jia-Horng Kao Ju-Hyun Kim Ting-Tsung Chang Kwan-Soo Byun Jyh-Jou Chen Sook-Hyang Jeong Tsung-Hui Hu Young-Seok Kim Cheng-Yuan Peng Won-Young Tak Horng-Yuan Wang Seung-Kew Yoon I.-Shyan Sheen Youn-Jae Lee Yu-Chun Hsu Hyung-Joon Yim Pei-Chien Tsai Ming-Lun Yeh Sang-Hoon Ahn Chia-Yen Dai Seung-Woon Paik Jee-Fu Huang Yoon-Jun Kim Wan-Long Chuang Young-Suk Lim Ming-Lung Yu |
| author_sort | Chung-Feng Huang |
| collection | DOAJ |
| description | Abstract Background/Aims Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C virus (HCV) infection. The long-term hepatic and extrahepatic outcomes of DAAs in chronic hepatitis C (CHC) patients receiving curative antivirals are elusive. Methods CHC patients were retrieved from two phase III sofosbuvir-based clinical trials conducted from 2013–2014. Patients who achieved a sustained virological response have been followed prospectively for 5 years since 2016. A propensity score-matched interferon-based historical control with a 1:3 ratio was used for comparison. Quality of life (QoL) was measured by the SF-36, liver fibrosis was measured by electrography, and fibrosis-related markers were followed annually in the prospective cohort. Results A total of 160 DAA- and 480 interferon-treated patients were enrolled. Twenty-eight patients developed hepatocellular carcinoma (HCC) over a follow-up period of 4424 person-years (annual incidence: 0.6%). The incidence of HCC did not differ significantly between the DAA cohort and interferon-treated patients (P = 0.07). Cox regression analysis revealed that FIB-4 was the only factor independently associated with HCC development (hazard ratio [HR]: 95% confidence interval [CI] 3.59/1.68–7.66, P = 0.001). The incidence of newly developed cardio-cerebrovascular disease was 13.8 per 1000 person-years and 0.9 per 1000 person-years in interferon-treated patients and the DAA cohort, respectively (P < 0.001). Interferon-based patients had a significantly greater incidence of cardio-cerebrovascular disease (HR/CI 3.39/1.28–8.96, P = 0.014). There was a substantial decrease in liver stiffness (P trend = 0.08) and M2BPGi (P trend = 0.05) and a significant reduction in LOXL2 (P trend = 0.02) over 5 years. A significant decrease in QoL was observed in role limitations due to physical health and emotional problems, whereas the other parameters were maintained consistently throughout the 5 years of follow-up. Conclusions HCV eradication by DAAs improved liver- and non-liver-related outcomes, constantly promoted liver fibrosis regression, and maintained quality of life after HCV cure. Clinical Trial Number NCT03042520. |
| format | Article |
| id | doaj-art-bf6c60ccc0f64e58b38a4d90a0ce0812 |
| institution | DOAJ |
| issn | 2193-8229 2193-6382 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Infectious Diseases and Therapy |
| spelling | doaj-art-bf6c60ccc0f64e58b38a4d90a0ce08122025-08-20T03:07:54ZengAdis, Springer HealthcareInfectious Diseases and Therapy2193-82292193-63822025-04-011451089110110.1007/s40121-025-01145-yLong-Term Hepatic and Extrahepatic Outcomes of Chronic Hepatitis C Patients After Sofosbuvir-Based Treatment (LONGHEAD Study)Chung-Feng Huang0Jeong Heo1Rong-Nan Chien2Yang-Hyun Baek3Jia-Horng Kao4Ju-Hyun Kim5Ting-Tsung Chang6Kwan-Soo Byun7Jyh-Jou Chen8Sook-Hyang Jeong9Tsung-Hui Hu10Young-Seok Kim11Cheng-Yuan Peng12Won-Young Tak13Horng-Yuan Wang14Seung-Kew Yoon15I.-Shyan Sheen16Youn-Jae Lee17Yu-Chun Hsu18Hyung-Joon Yim19Pei-Chien Tsai20Ming-Lun Yeh21Sang-Hoon Ahn22Chia-Yen Dai23Seung-Woon Paik24Jee-Fu Huang25Yoon-Jun Kim26Wan-Long Chuang27Young-Suk Lim28Ming-Lung Yu29Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDepartment of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University HospitalDepartment of Gastroenterology and Hepatology, Chang Gung Memorial HospitalDepartment of Internal Medicine, Dong-A University College of MedicineHepatitis Research Center and Department of Internal Medicine, National Taiwan University HospitalDepartment of Internal Medicine, Gachon University Gil HospitalDivision of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityDepartment of Internal Medicine, Korea University Guro Hospital, Korea University College of MedicineLiouying Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical CenterDepartment of Internal Medicine, Seoul National University Bundang HospitalDivision of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineDepartment of Internal Medicine, Bucheon Hospital, Soon Chun Hyang UniversityCenter for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, School of Medicine, China Medical UniversityDepartment of Internal Medicine, School of Medicine, Kyungpook National University HospitalDivision of Gastroenterology, Department of Internal Medicine, Taipei Mackay Memorial HospitalDepartment of Internal Medicine, Seoul St. Mary’s HospitalDepartment of Gastroenterology and Hepatology, Chang Gung Memorial HospitalDepartment of Internal Medicine, Inje University Busan Paik HospitalDepartment of Gastroenterology and Hepatology, Changhua Christian HospitalDepartment of Internal Medicine, Korea University Ansan HospitalHepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityHepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDepartment of Internal Medicine, Institute of Gastroenterology, Yonsei University College of MedicineHepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversitySungkyunkwan UniversityHepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversitySeoul National University HospitalHepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDepartment of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of MedicineHepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityAbstract Background/Aims Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C virus (HCV) infection. The long-term hepatic and extrahepatic outcomes of DAAs in chronic hepatitis C (CHC) patients receiving curative antivirals are elusive. Methods CHC patients were retrieved from two phase III sofosbuvir-based clinical trials conducted from 2013–2014. Patients who achieved a sustained virological response have been followed prospectively for 5 years since 2016. A propensity score-matched interferon-based historical control with a 1:3 ratio was used for comparison. Quality of life (QoL) was measured by the SF-36, liver fibrosis was measured by electrography, and fibrosis-related markers were followed annually in the prospective cohort. Results A total of 160 DAA- and 480 interferon-treated patients were enrolled. Twenty-eight patients developed hepatocellular carcinoma (HCC) over a follow-up period of 4424 person-years (annual incidence: 0.6%). The incidence of HCC did not differ significantly between the DAA cohort and interferon-treated patients (P = 0.07). Cox regression analysis revealed that FIB-4 was the only factor independently associated with HCC development (hazard ratio [HR]: 95% confidence interval [CI] 3.59/1.68–7.66, P = 0.001). The incidence of newly developed cardio-cerebrovascular disease was 13.8 per 1000 person-years and 0.9 per 1000 person-years in interferon-treated patients and the DAA cohort, respectively (P < 0.001). Interferon-based patients had a significantly greater incidence of cardio-cerebrovascular disease (HR/CI 3.39/1.28–8.96, P = 0.014). There was a substantial decrease in liver stiffness (P trend = 0.08) and M2BPGi (P trend = 0.05) and a significant reduction in LOXL2 (P trend = 0.02) over 5 years. A significant decrease in QoL was observed in role limitations due to physical health and emotional problems, whereas the other parameters were maintained consistently throughout the 5 years of follow-up. Conclusions HCV eradication by DAAs improved liver- and non-liver-related outcomes, constantly promoted liver fibrosis regression, and maintained quality of life after HCV cure. Clinical Trial Number NCT03042520.https://doi.org/10.1007/s40121-025-01145-yDAAHCVSVRLong-term outcome |
| spellingShingle | Chung-Feng Huang Jeong Heo Rong-Nan Chien Yang-Hyun Baek Jia-Horng Kao Ju-Hyun Kim Ting-Tsung Chang Kwan-Soo Byun Jyh-Jou Chen Sook-Hyang Jeong Tsung-Hui Hu Young-Seok Kim Cheng-Yuan Peng Won-Young Tak Horng-Yuan Wang Seung-Kew Yoon I.-Shyan Sheen Youn-Jae Lee Yu-Chun Hsu Hyung-Joon Yim Pei-Chien Tsai Ming-Lun Yeh Sang-Hoon Ahn Chia-Yen Dai Seung-Woon Paik Jee-Fu Huang Yoon-Jun Kim Wan-Long Chuang Young-Suk Lim Ming-Lung Yu Long-Term Hepatic and Extrahepatic Outcomes of Chronic Hepatitis C Patients After Sofosbuvir-Based Treatment (LONGHEAD Study) Infectious Diseases and Therapy DAA HCV SVR Long-term outcome |
| title | Long-Term Hepatic and Extrahepatic Outcomes of Chronic Hepatitis C Patients After Sofosbuvir-Based Treatment (LONGHEAD Study) |
| title_full | Long-Term Hepatic and Extrahepatic Outcomes of Chronic Hepatitis C Patients After Sofosbuvir-Based Treatment (LONGHEAD Study) |
| title_fullStr | Long-Term Hepatic and Extrahepatic Outcomes of Chronic Hepatitis C Patients After Sofosbuvir-Based Treatment (LONGHEAD Study) |
| title_full_unstemmed | Long-Term Hepatic and Extrahepatic Outcomes of Chronic Hepatitis C Patients After Sofosbuvir-Based Treatment (LONGHEAD Study) |
| title_short | Long-Term Hepatic and Extrahepatic Outcomes of Chronic Hepatitis C Patients After Sofosbuvir-Based Treatment (LONGHEAD Study) |
| title_sort | long term hepatic and extrahepatic outcomes of chronic hepatitis c patients after sofosbuvir based treatment longhead study |
| topic | DAA HCV SVR Long-term outcome |
| url | https://doi.org/10.1007/s40121-025-01145-y |
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