Clinical Epidemiology (Aug 2022)
Design for a Multicentre Prospective Cohort for the Assessment of Platelet Function in Patients with Hepatitis-B-Virus-Related Acute-on-Chronic Liver Failure
Abstract
Xiuhua Jiang,1,* Shiqi Chai,1,* Yan Huang,2,* Zuxiong Huang,3,* Wenting Tan,4,* Yanhang Gao,5,* Xiaobo Lu,6,* Zhongji Meng,7,* Huayou Zhou,8 Wenbing Kong,8 Xiaoting Tang,1 Yujun Tang,1 Tingting Qi,1 Chengjin Liao,2 Qiaorong Gan,3 Xiaomei Xiang,4 Yanan Zhang,5 Shuai Wang,6 Yuanyuan Chen,7 Jinjun Chen1,9 1Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 5Department of Hepatology, the First Hospital of Jilin University, Changchun, People’s Republic of China; 6Infectious Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 7Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China; 8Department of Blood Transfusion, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 9Hepatology Unit, Zengcheng Branch, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinjun Chen, Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Dadao Bei, Guangzhou, 510515, People’s Republic of China, Email [email protected]: Acute-on-chronic liver failure (ACLF) has high short-term mortality and lacks sufficient medical therapy. Available algorithms are unable to precisely predict short-term outcomes or safely stratify patients with ACLF as emergent liver transplantation candidates. Therefore, a personalized prognostic tool is urgently needed.Purpose: Platelet function and its clinical significance in ACLF patients with chronic hepatitis B virus (HBV) infection have not been investigated. This study aimed to assess changes in platelet function using thromboelastography (TEG) and platelet mapping (TEG-PM) in HBV-related ACLF patients.Methods: Chronic liver disease patients with acute decompensation or acute hepatic injury were recruited. The derivation cohort enrolled HBV-related patients at Nanfang Hospital. HBV-related and non-HBV-related patients were both enrolled in internal and external validation cohorts at seven university hospitals. TEG and TEG-PM were performed at baseline in the derivation cohort and baseline, day 7, and day 14 in the validation cohorts. The primary outcome was all-cause 28-day mortality. Status check and new-onset complications were recorded during the 3-month follow-up, but status check will extend to 5 years.Conclusion and Future Plans: In this study, 586 participants were enrolled, including 100 in derivation cohort, 133 in internal validation cohort, and 353 in external validation cohort. Biomaterials, including plasma, serum, urine, and some explanted liver tissues, were collected from these patients. A 3-month follow-up with survival status was completed. The baseline characteristics indicated that 51% of the patients had adenosine diphosphate (ADP)-hyporesponsive circulating platelets. The prognostic potential of platelet function will be explored in the derivation cohort (HBV-related ACLF patients) and further substantiated in the validation cohorts (HBV-related and non-HBV-related ACLF patients). Biosamples are currently used to explore the underlying mechanisms related to ADP-hyporesponsive platelets. The ongoing proteomic and metabolic analyses will provide new insights into the pathogenesis of extrahepatic organ failures in ACLF patients.Keywords: acute-on-chronic liver failure, coagulopathy failure, platelet function, thromboelastography, prognosis, study design