Design for a Multicentre Prospective Cohort for the Assessment of Platelet Function in Patients with Hepatitis-B-Virus-Related Acute-on-Chronic Liver Failure

Xiuhua Jiang; Shiqi Chai; Yan Huang; Zuxiong Huang; Wenting Tan; Yanhang Gao; Xiaobo Lu; Zhongji Meng; Huayou Zhou; Wenbing Kong; Xiaoting Tang; Yujun Tang; Tingting Qi; Chengjin Liao; Qiaorong Gan; Xiaomei Xiang; Yanan Zhang; Shuai Wang; Yuanyuan Chen; Jinjun Chen

doi:10.2147/CLEP.S376068

Design for a Multicentre Prospective Cohort for the Assessment of Platelet Function in Patients with Hepatitis-B-Virus-Related Acute-on-Chronic Liver Failure

Clin Epidemiol. 2022 Aug 24:14:997-1011. doi: 10.2147/CLEP.S376068. eCollection 2022.

Authors

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 Zhou⁸, Wenbing Kong⁸, Xiaoting Tang¹, Yujun Tang¹, Tingting Qi¹, Chengjin Liao², Qiaorong Gan³, Xiaomei Xiang⁴, Yanan Zhang⁵, Shuai Wang⁶, Yuanyuan Chen⁷, Jinjun Chen^{1

9}

Affiliations

¹ Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
² Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
³ Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China.
⁴ Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People's Republic of China.
⁵ Department of Hepatology, the First Hospital of Jilin University, Changchun, People's Republic of China.
⁶ Infectious Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China.
⁷ Department 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.
⁸ Department of Blood Transfusion, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
⁹ Hepatology Unit, Zengcheng Branch, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

^# Contributed equally.

Abstract

Background: 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; prognosis; study design; thromboelastography.

Grants and funding

This work was supported by the National Science and Technology Major Project (2018ZX10723203, 2018ZX10302206), National Natural Science Foundation of China (82070650), National Key Research and Development Program of China (2017YFC0908100), Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01S131), Clinical Research Program of Nanfang Hospital, Southern Medical University (2020CR026), Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2019ZD006), President Foundation of Nanfang Hospital, Southern Medical University (2019Z003) and Key-Area Research and Development Program of Guangdong Province (2019B020227004).