Journal of Shandong University (Health Sciences) ›› 2025, Vol. 63 ›› Issue (6): 89-99.doi: 10.6040/j.issn.1671-7554.0.2024.1354

• Clinical Medicine • Previous Articles    

Diagnostic value of blood cell count-related biomarkers in predicting 28-day mortality in acute-on-chronic hepatitis b liver failure

JIA Ruoxi1,2, LYU Li3, LIU Hanyun1, WU Yinping4, LI Fengcai2, ZHAO Zehua2, WANG Kai2, FAN Yuchen2   

  1. 1. Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China;
    2. Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    3. Department of Outpatient and Follow Up Center, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    4. Department of Infectious Diseases, Xian Central Hospital, Xian 710003, Shaanxi, China
  • Published:2025-07-08

PDF (PC)

16

Abstract: Objective To investigate the diagnostic value of blood cell count-related biomarkers in predicting 28-day morality in patients with acute-on-chronic hepatitis B liver failure(ACHBLF). Methods A total of 261 patients with ACHBLF were retrospectively included from January 2010 to July 2024. Univariate and multivariate Logistic regression analyses were performed to identify the risk factors, which were further evaluated by machine learning using XGBoost algorithm. The receiver operating characteristic(ROC)curve was analyzed to evaluate the prognostic accuracy and the calibration curve was used to evaluate the calibration. Furthermore, Kaplan-Meier survival analysis was performed to evaluate the performance of the model in diagnosing the 28-day mortality. Results There were 99(37.93%)patients who died within 28 days. Univariate Logistic regression analysis identified age, albumin, serum sodium, eosinophil ratio, eosinophil count, prothrombin activity(PTA), international normalized ratio(INR), total bilirubin(TBIL), model for end-stage liver disease(MELD)score,(neutrophil+monocyte)/lymphocyte ratio(NmLR), systemic inflammatory response index(SIRI), and neutrophil/platelet ratio(NPR)as risk factors. Multivariate Logistic regression analysis showed that SIRI(OR=1.15,95%CI:1.03-1.29,P=0.011)and MELD score(OR=1.23,95%CI:1.14-1.31,P<0.001)were independent risk factors for 28-day mortality. XGBoost algorithm showed that the SHAP values of SIRI and MELD score were 0.278 and 0.839, respectively. The area under the ROC curve(AUC)of SIRI was 0.693(95%CI: 0.628-0.758)with a specificity of 0.469 and a sensitivity of 0.828. In addition, the combination of SIRI and MELD score showed an AUC of 0.807(95%CI: 0.753-0.861)with a specificity of 0.722 and a sensitivity of 0.727. The calibration curve showed that the predicted probability was consistent with the actual probability. Kaplan-Meier analysis showed that patients with a combined diagnostic score above the cut-off value of 1.9 had a worse survival than those with a combined diagnostic score below 1.9(P=0.012). In ACHBLF patients diagnosed by Chinese criteria, the combination of SIRI and MELD score showed an AUC of 0.749(95%CI: 0.677-0.820)with a specificity of 0.677 and a sensitivity of 0.733, validating the performance of the combined model in predicting 28-day prognosis. Conclusion SIRI combined with MELD score has good diagnostic value for predicting 28-days mortality in ACHBLF.

Key words: Acute-on-chronic hepatitis B liver failure, Systemic inflammatory response index, Prognosis, Risk factor, Blood cell counts related biomarkers

CLC Number: 

  • R575.3
[1] Arroyo V, Moreau R, Jalan R, et al. Acute-on-chronic liver failure: a new syndrome that will re-classify cirrhosis[J]. J Hepatol, 2015, 62(1): 131-143.
[2] Yu XP, Yang FF, Shen ZL, et al. BTLA contributes to acute-on-chronic liver failure infection and mortality through CD4+ T-cell exhaustion[J]. Nat Commun, 2024, 15(1): 1835. doi:10.1038/s41467-024-46047-8
[3] 杨雪彦, 吴寅平, 吕丽, 等. 单核细胞与淋巴细胞比值动态变化对慢加急性乙型肝炎肝衰竭预后的诊断价值[J]. 山东大学学报(医学版), 2024, 62(3): 61-69. YANG Xueyan, WU Yinping, LYU Li, et al. Diagnostic value of dynamic changes of monocyte-to-lymphocyte ratio in acute-on-chronic hepatitis B liver failure[J]. Journal of Shandong University(Health Sciences), 2024, 62(3): 61-69.
[4] 中华医学会感染病学分会肝衰竭与人工肝学组,中华医学会肝病学分会重型肝病与人工肝学组.肝衰竭诊治指南(2024年版)[J]. 中华临床感染病杂志,2024,17(5): 321-339. Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology. Guidelines for the diagnosis and treatment of liver failure(2024 version)[J]. Chinese Journal of Clinical Infectious Diseases, 2024,17(5): 321-339.
[5] Li H, Chen LY, Zhang NN, et al. Characteristics, diagnosis and prognosis of acute-on-chronic liver failure in cirrhosis associated to hepatitis B[J]. Sci Rep, 2016, 6: 25487. doi:10.1038/srep25487
[6] Li JQ, Liang X, You SL, et al. Development and validation of a new prognostic score for hepatitis B virus-related acute-on-chronic liver failure[J]. J Hepatol, 2021, 75(5): 1104-1115. doi:10.1016/j.jhep.2021.05.026
[7] Tong JJ, Zhao W, Mu XY, et al. Predictive value of the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score in the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure[J]. Chin Med J, 2019, 132(13): 1541-1549.
[8] Larmann J, Handke J, Scholz AS, et al. Preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are associated with major adverse cardiovascular and cerebrovascular events in coronary heart disease patients undergoing non-cardiac surgery[J]. BMC Cardiovasc Disord, 2020, 20(1): 230. doi:10.1186/s12872-020-01500-6
[9] Durmus E, Kivrak T, Gerin F, et al. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio are predictors of heart failure[J]. Arq Bras Cardiol, 2015, 105(6): 606-613.
[10] Ye Z, Hu TY, Wang J, et al. Systemic immune-inflammation index as a potential biomarker of cardiovascular diseases: a systematic review and meta-analysis[J]. Front Cardiovasc Med, 2022, 9: 933913. doi:10.3389/fcvm.2022.933913
[11] Modica R, Minotta R, Liccardi A, et al. Evaluation of neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR)and systemic immune-inflammation index(SII)as potential biomarkers in patients with sporadic medullary thyroid cancer(MTC)[J]. J Pers Med, 2023, 13(6): 953. doi:10.3390/jpm13060953
[12] Lin ZQ, Ma C, Cao WZ, et al. Prognostic significance of NLR, PLR, LMR and tumor infiltrating T lymphocytes in patients undergoing surgical resection for hilar cholangiocarcinoma[J]. Front Oncol, 2022, 12: 908907. doi:10.3389/fonc.2022.908907
[13] Gambardella C, Mongardini FM, Paolicelli M, et al. Role of inflammatory biomarkers(NLR, LMR, PLR)in the prognostication of malignancy in indeterminate thyroid nodules[J]. Int J Mol Sci, 2023, 24(7): 6466. doi:10.3390/ijms24076466
[14] Kovács AR, Sulina A, Kovács KS, et al. Prognostic significance of preoperative NLR, mLR, and PLR values in predicting the outcome of primary cytoreductive surgery in serous epithelial ovarian cancer[J]. Diagnostics, 2023, 13(13): 2268. doi:10.3390/diagnostics13132268
[15] Maloney S, Pavlakis N, Itchins M, et al. The prognostic and predictive role of the neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and lymphocyte-to-monocyte ratio(LMR)as biomarkers in resected pancreatic cancer[J]. J Clin Med, 2023, 12(5): 1989. doi:10.3390/jcm12051989
[16] Brito GMC, Fontenele AMM, Carneiro ECRL, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in nondialysis chronic kidney patients[J]. Int J Inflam, 2021, 2021: 6678960. doi:10.1155/2021/6678960
[17] Mure?瘙塂an AV, Russu E, Arb ana?瘙塂i EM, et al. The predictive value of NLR, MLR, and PLR in the outcome of end-stage kidney disease patients[J]. Biomedicines, 2022, 10(6): 1272. doi:10.3390/biomedicines10061272
[18] 邓婷婷, 李莉, 关瀛, 等. 炎性相关标志物判断HBV相关慢加急性肝衰竭预后的研究进展[J]. 临床肝胆病杂志, 2022, 38(10): 2346-2351. DENG Tingting, LI Li, GUAN Ying, et al. Research advances in inflammatory markers in predicting the prognosis of patients with HBV-related acute-on-chronic liver failure[J]. Journal of Clinical Hepatology, 2022, 38(10): 2346-2351.
[19] World Medical Association. World medical association declaration of Helsinki: ethical principles for medical research involving human participants[J]. JAMA, 2025, 333(1): 71-74. doi:10.1001/jama.2024.21972
[20] Sarin SK, Choudhury A, Sharma MK, et al. Acute-on-chronic liver failure: consens-us recommendations of the Asian Pacific association for the study of the liver(APASL): an update[J]. Hepatol Int, 2019, 13(4): 353-390. doi:10.1007/s12072-019-09946-3
[21] 中国医药生物技术协会药物性肝损伤防治技术专业委员会, 中华医学会肝病学分会药物性肝病学组. 中国药物性肝损伤诊治指南(2023年版)[J]. 中华肝脏病杂志, 2023, 31(4): 355-384. Technology Committee on DILI Prevention and Management, Chinese Medical Biotechnology Association; Study Group of Drug-Induced Liver Disease, Chinese Medical Association for the Study of Liver Diseases. Chinese guideline for diagnosis and management of drug-induced liver injury(2023 version)[J]. Chinese Journal of Hepatology,2023, 31(4): 355-384.
[22] 中华医学会肝病学分会. 自身免疫性肝炎诊断和治疗指南(2021)[J]. 中华肝脏病杂志, 2022, 30(5): 482-492. Chinese Society of Hepatology, Chinese Medical Association.Guidelines on the diagnosis and management of autoimmune hepatitis(2021)[J]. Chinese Journal of Hepatology,2022, 30(5): 482-492.
[23] 尤红, 段维佳, 李淑香, 等. 原发性胆汁性胆管炎的诊断和治疗指南(2021)[J]. 临床肝胆病杂志, 2022, 38(1): 35-41. YOU Hong, DUAN Weijia, LI Shuxiang, et al. Guidelines on the diagnosis and management of primary biliary cholangitis(2021)[J]. Journal of Clinical Hepatology, 2022, 38(1): 35-41.
[24] 中国医师协会脂肪性肝病专家委员会, 中华医学会肝病学分会脂肪肝和酒精性肝病学组. 酒精性肝病防治指南(2018年更新版)[J]. 临床肝胆病杂志, 2018, 34(5): 939-946. Fatty Liver Expert Committee,Chinese Medical Doctor Association, National Worksh-op on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology,Chi-nese Medical Association. Guidelines of prevention and treatment for alcoholic liver disease:a 2018 update[J]. J Clin Hepatol, 2018, 34(5): 939-946.
[25] Kamath PS, Kim WR; Advanced Liver Disease Stady Group. The model for end-stage liver disease(MELD)[J]. Hepatology, 2007, 45(3): 797-805.
[26] Piano S, Mahmud N, Caraceni P, et al. Mechanisms and treatment approaches for ACLF[J]. Liver Int, 2025, 45(3): e15733. doi: 10.1111/liv.15733
[27] Zhang Y, Tan WT, Wang XB, et al. Metabolic biomarkers significantly enhance the prediction of HBV-related ACLF occurrence and outcomes[J]. J Hepatol, 2023, 79(5): 1159-1171.
[28] Br VK, Sarin SK. Acute-on-chronic liver failure: terminology, mechanisms and management[J]. Clin Mol Hepatol, 2023, 29(3): 670-689.
[29] Cai JJ, Wang K, Han T, et al. Evaluation of prognostic values of inflammation-based makers in patients with HBV-related acute-on-chronic liver failure[J]. Medicine, 2018, 97(46): e13324. doi:10.1097/MD.0000000000013324
[30] Wang N, He SK, Zheng Y, et al. The value of NLR versus mLR in the short-term prognostic assessment of HBV-related acute-on-chronic liver failure[J]. Int Immunopharmacol, 2023, 121: 110489. doi:10.1016/j.intimp.2023.110489
[31] 徐华谦, 李雪, 汤善宏. 炎症反应在慢加急性肝衰竭中的作用及治疗策略[J]. 临床肝胆病杂志, 2022, 38(8): 1927-1930. XU Huaqian, LI Xue, TANG Shanhong. Research advances in the role of inflammatory response and related treatment strategies in acute-on-chronic liver failure[J]. Journal of Clinical Hepatology, 2022, 38(8): 1927-1930.
[32] Xu YY, He HJ, Zang YS, et al. Systemic inflammation response index(SIRI)as a novel biomarker in patients with rheumatoid arthritis: a multi-center retrospective study[J]. Clin Rheumatol, 2022, 41(7): 1989-2000.
[33] Rajakumar HK, Coimbatore Sathyabal V, Vasanthan M, et al. The predictive role of systemic inflammation response index(SIRI), neutrophil-lymphocyte ratio(NLR), and platelet-lymphocyte ratio(PLR)in the prognosis of acute coronary syndrome in a tertiary care hospital[J]. Heliyon, 2024, 10(20): e39029. doi:10.1016/j.heliyon.2024.e39029
[34] Cui SP, Cao S, Chen Q, et al. Preoperative systemic inflammatory response index predicts the prognosis of patients with hepatocellular carcinoma after liver transplantation[J]. Front Immunol, 2023, 14: 1118053. doi:10.3389/fimmu.2023.1118053
[35] 高金梅, 黄映波, 冯珍珍. 单核细胞趋化蛋白-1对67例全身炎症反应综合征患者的诊断价值[J]. 山东大学学报(医学版), 2021, 59(10): 75-79. GAO Jinmei, HUANG Yingbo, FENG Zhenzhen. Diagnostic value of monocyte chemoattractant protein-1 in 67 patients with systemic inflammatory response syndrome[J]. Journal of Shandong University(Health Sciences), 2021, 59(10): 75-79.
[1] ZHANG Zheng, WANG Jianwei, YANG Yujuan, ZHANG Yu, SONG Xicheng. Immunoglobulin E changes and risk factors in asthma children between 2008 and 2019 [J]. Journal of Shandong University (Health Sciences), 2025, 63(7): 32-36.
[2] LIU Baoguo, SONG Xiang, ZHAO Xiaowen, MAO Yali. Application value of serum STAT5B and NKAIN1 mRNA detection in breast cancer [J]. Journal of Shandong University (Health Sciences), 2025, 63(7): 68-74.
[3] WANG Lei, CHANG Xiao, WANG Zimeng, LI Jiaojiao, CUI Shujun, YANG Fei, ZHU Yuexiang. Predictive value of intratumoral and peritumoral DCE-MRI imaging histology for progression-free survival in patients with cervical cancer [J]. Journal of Shandong University (Health Sciences), 2025, 63(6): 45-54.
[4] DU Xue, LI Chunxia, LIU Yunxia, ZHANG Tao. Dynamic prediction model for the colorectal cancer patients prognosis based on MFPC-Cox [J]. Journal of Shandong University (Health Sciences), 2025, 63(5): 101-110.
[5] LI Jing, HAO Panpan. Association between the heart rate variation and the prognosis in patients with acute heart failure at hospital admission and discharge [J]. Journal of Shandong University (Health Sciences), 2025, 63(4): 75-82.
[6] YANG Weifang, XU Hong, LIU Yuantao, ZHAO Huichen. Mechanism of thyroid-stimulating immunoglobulin in Graves disease recurrence and clinical significance [J]. Journal of Shandong University (Health Sciences), 2025, 63(4): 116-121.
[7] CHENG Yueqi, WANG Fei, YU Lixiang, ZHENG Chao, YU Zhigang. Progress in the study of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients [J]. Journal of Shandong University (Health Sciences), 2025, 63(1): 17-24.
[8] WANG Zheyu, XU Yi, ZHAO Changbo, YANG Shuofei, NI Qihong, CHEN Jiaquan, WANG Weilun, LI Yinan, GUO Xiangjiang, YE Meng, ZHANG Lan, XUE Guanhua. Risk factors and management for iliac branch occlusion after endovascular abdominal aortic aneurysm repair [J]. Journal of Shandong University (Health Sciences), 2024, 62(9): 101-107.
[9] GUO Shuhua, FAN Yang, TIAN Feng, WANG Chuanxin, DU Lutao, LI Peilong, GUO Xing, XU Shuo. Role of microfibril-associated protein 3 in regulating mesenchymal transition of glioma stem cells [J]. Journal of Shandong University (Health Sciences), 2024, 62(6): 9-16.
[10] WEI Yanruoxue, LI Ziqi, LIU Chuncheng, LIU Xiaohan, ZHAO Ran, LIU Yukun. Intratumor heterogeneity of SP1 expression in colorectal cancer and its clinical significance [J]. Journal of Shandong University (Health Sciences), 2024, 62(5): 89-94.
[11] LIU Chuncheng, LIU Xiaohan, WEI Yanruoxue, LI Ziqi, LIU Yukun, ZHAO Ran. Subcellular localization pattern of bromodomain containing 9 in colorectal cancer and its clinical significance [J]. Journal of Shandong University (Health Sciences), 2024, 62(4): 24-30.
[12] GUO Xin, MENG Jun, ZHENG Shiliang, DONG Xiuhong. Correlation between frailty and body composition in elderly patients with gastric cancer [J]. Journal of Shandong University (Health Sciences), 2024, 62(4): 40-47.
[13] LI Jian, SUN Yun. Risk factors for death within 2 years in new maintenance haemodialysis patients [J]. Journal of Shandong University (Health Sciences), 2024, 62(4): 48-53.
[14] YANG Xueyan, WU Yinping, LYU Li, ZHAO Zehua, MA Hangyu, LI Fengcai, WANG Kai, FAN Yuchen. Diagnostic value of dynamic changes of monocyte-to-lymphocyte ratio in acute-on-chronic hepatitis B liver failure [J]. Journal of Shandong University (Health Sciences), 2024, 62(3): 61-69.
[15] DIAO Yujie, LIN Lin, LI Wenxuan, WANG Zhouyang, JIANG Bei, HU Yingying, LIU Guangyi. Neutrophil-to-platelet ratio predicts adverse renal outcomes in anti-neutrophil cytoplasmic antibody-associated vasculitis and its synergistic multifactor optimization model [J]. Journal of Shandong University (Health Sciences), 2024, 62(2): 60-68.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd