Ji-Hui Li,1 Yuna Tang,1 Jing Wang,1 Xue-Fei Wei,1 Na Wang,2 Jing-Wei Wang,2 Hui Lyu,3 Xue-Mei Jiang,4 Hui-Hui Liu,1,5 Kai Wang1,5,6 

1Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Hepatology, Qilu Hospital of Shandong University (Qingdao), Qingdao, Shandong, People’s Republic of China; 3Department of Severe Liver Disease, Shandong Public Health Clinical Center of Shandong University, Jinan, Shandong, People’s Republic of China; 4Department of Hepatology, Shandong Public Health Clinical Center of Shandong University, Jinan, Shandong, People’s Republic of China; 5Institute of Hepatology, Shandong University, Jinan, Shandong, People’s Republic of China; 6Shenzhen Research Institute, Shandong University, Shenzhen, Guangdong, People’s Republic of China

Correspondence: Hui-Hui Liu, Department of Hepatology, Qilu Hospital of Shandong University and Institute of Hepatology, Shandong University, Jinan, Shandong, People’s Republic of China, Email liuhuihui_2017@163.com Kai Wang, Department of Hepatology, Qilu Hospital of Shandong University and Institute of Hepatology, Shandong University, Jinan, Shandong, People’s Republic of China, Email wangdoc2010@163.com

Purpose: The study aimed to quantitatively detect the suppressors of cytokine signaling (SOCS) 3 promoter methylation levels, investigate the relationship between SOCS3 methylation and gene expression, and construct a prognosis prediction model combined with clinical indicators for Acute-on-chronic Hepatitis B Liver Failure (ACHBLF).
Methods: A total of 135 ACHBLF patients were enrolled and randomly divided into the training cohort and validation cohort. The SOCS3 mRNA and promoter methylation in peripheral blood mononuclear cells (PBMCs) of ACHBLF patients were quantitative measured. A clinical prediction model was established based on SOCS3 promoter methylation and clinical indicators. The prediction model was evaluated by the area under the receiver operating characteristic curve, the Hosmer-Lemeshow (H-L) goodness-of-fit test, and decision curve analysis.
Results: In this study, compared with ACHBLF survivals, SOCS3 showed lower mRNA levels and higher methylation levels in ACHBLF non-survivals. The SOCS3 methylation rates were negatively correlated with SOCS3 mRNA levels. PT-INR, IL-6, and percentage of the methylation reference (PMR) value (SOCS3) were used to establish a clinical model for predicting ACHBLF patients’ prognosis. The results of AUC, the Hosmer-Lemeshow (H-L) goodness-of-fit test and decision curve analysis (DCA) showed that the prediction model had good clinical applicability. The prediction model was visualized.
Conclusion: A prognosis prediction model for ACHBLF was developed based on PMR (SOCS3), PT-INR and IL-6, which may have a good potential clinical application value.

Keywords: acute-on-chronic hepatitis B liver failure, DNA methylation, prediction model, SOCS3