Development and validation of a novel prognostic model to predict 1-year post-transplant mortality for acute-on-chronic hepatitis B liver failure: a nationwide, multicentre, cohort studyResearch in context
Summary: Background: Liver transplantation (LT) provides a potential cure for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop and externally validate a prognostic model to predict 1-year post-LT mortality in patients with HBV-ACLF. Methods: This retrospectiv...
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2025-08-01
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| author | Li Zhuang Yimou Lin Yu Jia Jun Fang Yujian Zheng Taishi Fang Meiching Ong Aibo Mu Jiaxing Zhu Mengchao Wang Dong Zhao Feiwen Deng Qiucheng Lei Leibo Xu Zuozhong Yang Qiang Sun Wei Qu Chenwei Xu Zhijun Zhu Chuanjiang Li Hanyu Jiang Jimin Liu Xiaoshun He Shusen Zheng Zhiyong Guo Qi Ling |
| author_facet | Li Zhuang Yimou Lin Yu Jia Jun Fang Yujian Zheng Taishi Fang Meiching Ong Aibo Mu Jiaxing Zhu Mengchao Wang Dong Zhao Feiwen Deng Qiucheng Lei Leibo Xu Zuozhong Yang Qiang Sun Wei Qu Chenwei Xu Zhijun Zhu Chuanjiang Li Hanyu Jiang Jimin Liu Xiaoshun He Shusen Zheng Zhiyong Guo Qi Ling |
| author_sort | Li Zhuang |
| collection | DOAJ |
| description | Summary: Background: Liver transplantation (LT) provides a potential cure for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop and externally validate a prognostic model to predict 1-year post-LT mortality in patients with HBV-ACLF. Methods: This retrospective, nationwide, observational cohort study was conducted at ten high-volume LT centres in China. 4378 adult patients who underwent primary LT between January 2015 and December 2021 were screened, and those with HBV-ACLF according to the COSSH-ACLF criteria (separated into three ACLF grades based on the number of organ failures) were included. The HBV-ACLF LT (HALT) model was developed in the derivation cohort and validated in the external testing cohort. The derivation cohort were derived from two LT centres in one province (Zhejiang). The external testing cohort were derived from eight LT centres in two provinces. For model development, univariable Cox regression analysis was used to identify risk factors associated with 1-year post-LT mortality. Variables with univariable p < 0.05 were entered into the least absolute shrinkage and selection operator (Lasso) analysis for further feature selection. 10-fold cross validation was used to choose the optimal lambda (penalty for the number of features) of the Lasso model. Multivariable Cox regression was applied to construct the HALT model based on the risk factors selected by Lasso analysis. Primary outcome was survival rate at 1-year after LT. Secondary outcomes were short-term (28- and 90-day) and long-term survival after LT (3- and 5-year). Model performance was compared with eight other models (COSSH-ACLF II, COSSH-ACLF, CLIF-C ACLF, AARC, MELD, MELD-Na, SALT-M and TAM scores), using receiver operating characteristic curve and C-index values. A nomogram was developed to analyse the probability of the primary outcome in different graft-recipient combinations based on recipient factors (age, number of organ failures [OF], lactate) and graft factors (donation after circulatory death [DCD] and cold ischaemia time [CIT]). Findings: Between Jan 1, 2015, and Dec 1, 2021, 668 patients were included (derivation cohort, n = 418; external testing cohort, n = 250), with survival rates of 88.0%, 81.1%, 77.5%, 75.6% and 72.1% at 28-day, 90-day, 1-year, 3-year and 5-year post-LT, respectively. Three recipient’s factors (age, number of OF and arterial lactate concentration) as well as two graft’s parameters (DCD and CIT) were independently associated with 1-year post-LT mortality in the derivation cohort (all p < 0.05). The HALT model was established accordingly, showing better discriminative performance (C-index, 0.791) than eight current models in the external testing cohort (C-index, 0.529–0.627; all p < 0.001). If the sickest patients (age >55 years, OFs ≥3 and lactate ≥2.5 mmol/L) received high-risk grafts (DCD and CIT >10 h), the estimated 1-year post-LT mortality was 85.6%. Interpretation: The HALT model showed superior predictive ability over eight current models and may help for LT candidate selection and optimal organ allocation. Though the findings need to be verified in prospective studies and among different patient populations. Funding: This work was supported by grants from the National Natural Science Foundation of China, Natural Science Foundation of Zhejiang Province, and the Research Project of Jinan Microecological Biomedicine Shandong Laboratory. |
| format | Article |
| id | doaj-art-ecfb3274190b42bda082576d3ddca2ba |
| institution | OA Journals |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
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| spelling | doaj-art-ecfb3274190b42bda082576d3ddca2ba2025-08-20T02:38:51ZengElsevierEClinicalMedicine2589-53702025-08-018610336510.1016/j.eclinm.2025.103365Development and validation of a novel prognostic model to predict 1-year post-transplant mortality for acute-on-chronic hepatitis B liver failure: a nationwide, multicentre, cohort studyResearch in contextLi Zhuang0Yimou Lin1Yu Jia2Jun Fang3Yujian Zheng4Taishi Fang5Meiching Ong6Aibo Mu7Jiaxing Zhu8Mengchao Wang9Dong Zhao10Feiwen Deng11Qiucheng Lei12Leibo Xu13Zuozhong Yang14Qiang Sun15Wei Qu16Chenwei Xu17Zhijun Zhu18Chuanjiang Li19Hanyu Jiang20Jimin Liu21Xiaoshun He22Shusen Zheng23Zhiyong Guo24Qi Ling25Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China; Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou 310000, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310000, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310000, ChinaDepartment of Hepatobiliary Surgery & Liver Transplantation Centre, General Hospital of Southern Theatre Command, Guangzhou 510010, ChinaDivision of Liver Surgery and Organ Transplantation Centre, Shenzhen Third People’s Hospital, Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Centre for Infectious Disease, Shenzhen 518112, ChinaDepartment of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310000, ChinaDepartment of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310000, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Hepatobiliary Surgery & Liver Transplantation Centre, General Hospital of Southern Theatre Command, Guangzhou 510010, ChinaDivision of Liver Surgery and Organ Transplantation Centre, Shenzhen Third People’s Hospital, Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Centre for Infectious Disease, Shenzhen 518112, ChinaDepartment of Liver Surgery, The First People’s Hospital of Foshan, Foshan 528010, ChinaDepartment of Liver Surgery, The First People’s Hospital of Foshan, Foshan 528010, ChinaDepartment of Pancreato-Biliary Surgery and Liver Transplantation Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Pancreato-Biliary Surgery and Liver Transplantation Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of General Surgery, Zhongshan People’s Hospital, Zhongshan 528403, ChinaLiver Transplantation Centre, National Clinical Research Centre for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100000, ChinaLiver Transplantation Centre, National Clinical Research Centre for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100000, ChinaLiver Transplantation Centre, National Clinical Research Centre for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100000, ChinaDivision of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Radiology, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Pathology and Laboratory Medicine, Mt Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, CanadaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China; Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou 310000, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310000, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, National Medical Centre for Infectious Diseases, Hangzhou 310000, ChinaOrgan Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Corresponding author. Address: 58 Zhongshan Er Road, Guangzhou 510080, China.Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310000, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, National Medical Centre for Infectious Diseases, Hangzhou 310000, China; Corresponding author. Address: 79 Qingchun Road, Hangzhou 310000, China.Summary: Background: Liver transplantation (LT) provides a potential cure for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop and externally validate a prognostic model to predict 1-year post-LT mortality in patients with HBV-ACLF. Methods: This retrospective, nationwide, observational cohort study was conducted at ten high-volume LT centres in China. 4378 adult patients who underwent primary LT between January 2015 and December 2021 were screened, and those with HBV-ACLF according to the COSSH-ACLF criteria (separated into three ACLF grades based on the number of organ failures) were included. The HBV-ACLF LT (HALT) model was developed in the derivation cohort and validated in the external testing cohort. The derivation cohort were derived from two LT centres in one province (Zhejiang). The external testing cohort were derived from eight LT centres in two provinces. For model development, univariable Cox regression analysis was used to identify risk factors associated with 1-year post-LT mortality. Variables with univariable p < 0.05 were entered into the least absolute shrinkage and selection operator (Lasso) analysis for further feature selection. 10-fold cross validation was used to choose the optimal lambda (penalty for the number of features) of the Lasso model. Multivariable Cox regression was applied to construct the HALT model based on the risk factors selected by Lasso analysis. Primary outcome was survival rate at 1-year after LT. Secondary outcomes were short-term (28- and 90-day) and long-term survival after LT (3- and 5-year). Model performance was compared with eight other models (COSSH-ACLF II, COSSH-ACLF, CLIF-C ACLF, AARC, MELD, MELD-Na, SALT-M and TAM scores), using receiver operating characteristic curve and C-index values. A nomogram was developed to analyse the probability of the primary outcome in different graft-recipient combinations based on recipient factors (age, number of organ failures [OF], lactate) and graft factors (donation after circulatory death [DCD] and cold ischaemia time [CIT]). Findings: Between Jan 1, 2015, and Dec 1, 2021, 668 patients were included (derivation cohort, n = 418; external testing cohort, n = 250), with survival rates of 88.0%, 81.1%, 77.5%, 75.6% and 72.1% at 28-day, 90-day, 1-year, 3-year and 5-year post-LT, respectively. Three recipient’s factors (age, number of OF and arterial lactate concentration) as well as two graft’s parameters (DCD and CIT) were independently associated with 1-year post-LT mortality in the derivation cohort (all p < 0.05). The HALT model was established accordingly, showing better discriminative performance (C-index, 0.791) than eight current models in the external testing cohort (C-index, 0.529–0.627; all p < 0.001). If the sickest patients (age >55 years, OFs ≥3 and lactate ≥2.5 mmol/L) received high-risk grafts (DCD and CIT >10 h), the estimated 1-year post-LT mortality was 85.6%. Interpretation: The HALT model showed superior predictive ability over eight current models and may help for LT candidate selection and optimal organ allocation. Though the findings need to be verified in prospective studies and among different patient populations. Funding: This work was supported by grants from the National Natural Science Foundation of China, Natural Science Foundation of Zhejiang Province, and the Research Project of Jinan Microecological Biomedicine Shandong Laboratory.http://www.sciencedirect.com/science/article/pii/S2589537025002974Hepatitis B-Related acute-on-chronic liver failureLiver transplantationPost-transplant mortalityPrognostic modelGraft-recipient combination |
| spellingShingle | Li Zhuang Yimou Lin Yu Jia Jun Fang Yujian Zheng Taishi Fang Meiching Ong Aibo Mu Jiaxing Zhu Mengchao Wang Dong Zhao Feiwen Deng Qiucheng Lei Leibo Xu Zuozhong Yang Qiang Sun Wei Qu Chenwei Xu Zhijun Zhu Chuanjiang Li Hanyu Jiang Jimin Liu Xiaoshun He Shusen Zheng Zhiyong Guo Qi Ling Development and validation of a novel prognostic model to predict 1-year post-transplant mortality for acute-on-chronic hepatitis B liver failure: a nationwide, multicentre, cohort studyResearch in context EClinicalMedicine Hepatitis B-Related acute-on-chronic liver failure Liver transplantation Post-transplant mortality Prognostic model Graft-recipient combination |
| title | Development and validation of a novel prognostic model to predict 1-year post-transplant mortality for acute-on-chronic hepatitis B liver failure: a nationwide, multicentre, cohort studyResearch in context |
| title_full | Development and validation of a novel prognostic model to predict 1-year post-transplant mortality for acute-on-chronic hepatitis B liver failure: a nationwide, multicentre, cohort studyResearch in context |
| title_fullStr | Development and validation of a novel prognostic model to predict 1-year post-transplant mortality for acute-on-chronic hepatitis B liver failure: a nationwide, multicentre, cohort studyResearch in context |
| title_full_unstemmed | Development and validation of a novel prognostic model to predict 1-year post-transplant mortality for acute-on-chronic hepatitis B liver failure: a nationwide, multicentre, cohort studyResearch in context |
| title_short | Development and validation of a novel prognostic model to predict 1-year post-transplant mortality for acute-on-chronic hepatitis B liver failure: a nationwide, multicentre, cohort studyResearch in context |
| title_sort | development and validation of a novel prognostic model to predict 1 year post transplant mortality for acute on chronic hepatitis b liver failure a nationwide multicentre cohort studyresearch in context |
| topic | Hepatitis B-Related acute-on-chronic liver failure Liver transplantation Post-transplant mortality Prognostic model Graft-recipient combination |
| url | http://www.sciencedirect.com/science/article/pii/S2589537025002974 |
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