Zhang Nan, Wu Hai-Shi, Pang Xiu-Qing, Yu Cheng-You, Li Xing, Gao Zhi-Liang
Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China.
Guangdong Key laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China.
BMC Gastroenterol. 2025 May 26;25(1):405. doi: 10.1186/s12876-025-03995-9.
Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is characterized by immune dysregulation and systemic inflammation, which lead to high mortality. Although immunosuppressive CD45 erythroid progenitor cells (EPCs) percentages are elevated in chronic hepatitis B (CHB) and are associated with disease progression, their role in HBV-ACLF remains unclear. This study aims to evaluate the impact of CD45 EPCs on disease progression in patients with HBV-ACLF.
In this retrospective study, we analyzed the data of 102 patients with CHB and 65 patients with HBV-ACLF receiving standard drugs treatment from the Third Affiliated Hospital of Sun Yat-sen University between January 2021 and December 2023. HBV-ACLF diagnosis followed the Chinese Group on the Study of Severe Hepatitis B-Acute-on-Chronic Liver Failure criteria, with strict exclusion of comorbidities. Peripheral blood mononuclear cells (PBMCs) were isolated via density gradient centrifugation, and CD45 EPCs (CD45 CD71 CD235a) were quantified using flow cytometry. Liver tissue EPCs were assessed by immunofluorescence in biopsy/transplant specimens. Receiver operating characteristic (ROC) and multivariable logistic regression analyses identified prognostic factors associated with disease progression.
Our findings revealed that patients with HBV-ACLF had significantly elevated percentages of CD45 EPCs compared with those with CHB. We also observed strong correlations between CD45 EPC percentages and creatinine concentration, leukocyte count, and neutrophil-to-lymphocyte ratio (NLR). The area under the ROC curve for CD45 EPCs was 0.718, indicating a significant predictive value [95% confidence interval (CI): 0.586-0.851, p = 0.004]. High CD45 EPC percentage was associated with a greater incidence of hepatic encephalopathy (30.8% vs. 10.3%, p = 0.037) and higher rates of disease progression (73.1% vs. 35.9%, p = 0.003). Multivariate logistic regression analysis identified international normalized ratio (INR) and NLR as independent predictors of poor 28-day outcomes (INR odds ratio [OR] = 6.098, p < 0.001; NLR OR = 1.354, p = 0.005).
The percentage of CD45 EPCs in PBMCs may be a potential biomarker for predicting 28-day disease progression in patients with HBV-ACLF. These findings highlight their possible clinical utility for risk stratification.
乙型肝炎病毒相关慢加急性肝衰竭（HBV-ACLF）的特征是免疫失调和全身炎症，这导致高死亡率。尽管慢性乙型肝炎（CHB）患者中免疫抑制性CD45红系祖细胞（EPCs）百分比升高且与疾病进展相关，但其在HBV-ACLF中的作用仍不清楚。本研究旨在评估CD45 EPCs对HBV-ACLF患者疾病进展的影响。
在这项回顾性研究中，我们分析了2021年1月至2023年12月期间在中山大学附属第三医院接受标准药物治疗的102例CHB患者和65例HBV-ACLF患者的数据。HBV-ACLF的诊断遵循中国重型乙型肝炎-慢加急性肝衰竭研究组的标准，严格排除合并症。通过密度梯度离心分离外周血单个核细胞（PBMCs），并使用流式细胞术对CD45 EPCs（CD45 CD71 CD235a）进行定量。通过活检/移植标本中的免疫荧光评估肝组织EPCs。受试者工作特征（ROC）和多变量逻辑回归分析确定了与疾病进展相关的预后因素。
我们的研究结果显示，与CHB患者相比，HBV-ACLF患者的CD45 EPCs百分比显著升高。我们还观察到CD45 EPCs百分比与肌酐浓度、白细胞计数和中性粒细胞与淋巴细胞比值（NLR）之间存在强相关性。CD45 EPCs的ROC曲线下面积为0.718，表明具有显著的预测价值[95%置信区间（CI）：0.586-0.851，p = 0.004]。高CD45 EPCs百分比与肝性脑病的发生率更高（30.8%对10.3%，p = 0.037）和疾病进展率更高（73.1%对35.9%，p = 0.003）相关。多变量逻辑回归分析确定国际标准化比值（INR）和NLR为28天不良结局的独立预测因素（INR比值比[OR] = 6.098，p < 0.001；NLR OR = 1.354，p = 0.005）。
PBMCs中CD45 EPCs的百分比可能是预测HBV-ACLF患者28天疾病进展的潜在生物标志物。这些发现突出了它们在风险分层方面可能的临床应用价值。
