Wang Neng, Zheng Yu, Tao Shuai, Chen Liang
Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
BMC Gastroenterol. 2025 Jul 1;25(1):444. doi: 10.1186/s12876-025-04004-9.
This study aimed to elucidate the correlations among dyslipidemia, immune function, and clinical outcomes in patients with acute-on-chronic liver failure (ACLF), with particular emphasis on the clinical significance of lipid metabolism and cellular immune parameters in hepatitis B virus-associated ACLF (HBV-ACLF).
A retrospective analysis was conducted on 803 patients with HBV-ACLF admitted to the Shanghai Public Health Clinical Center from January 2014 to January 2024. Patients were stratified into deceased (n = 414) and survival (n = 389) groups based on clinical outcomes. Clinical baseline data, lipid metabolic indices, and cellular immune parameters were collected. The Spearman correlation coefficient was utilized to assess the correlation between lipid metabolic indices and cellular immune parameters, and a multivariate Cox proportional hazards model was applied to analyze risk factors for mortality.
Compared to the survival group, lipid metabolism indices in the deceased group were significantly reduced (P < 0.05). Lipid metabolism indices, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (APOA1), apolipoprotein B (APOB), total cholesterol (TC), and triglycerides (TG), demonstrated significant negative correlations with the severity of liver failure (P < 0.05). Correlation analysis with lymphocyte subset counts revealed positive correlations between low-density lipoprotein, TG, TC, APOB, and CD3 + T cells, CD4 + T cells, CD8 + T cells, and CD45 + T cells (P < 0.05). APOA1 and HDL-C were positively correlated with B cells and NK cells (P < 0.05). TG and APOB showed significant negative correlations with the CD4/CD8 ratio (P < 0.05). Multivariate Cox analysis identified age, creatinine, total bilirubin, international normalized ratio (INR), hepatic encephalopathy, and hepatorenal syndrome as independent risk factors affecting the short-term prognosis of HBV-ACLF, while sodium, APOA1, and APOB were identified as independent protective factors for ACLF (HR = 0.984, 95% CI: 0.974-0.995, P < 0.001, HR = 0.267,95% CI: 0.120-0.596, P = 0.001, HR = 0.486, 95% CI: 0.282-0.838, P = 0.010).
Patients with HBV-ACLF exhibit decreased levels of TC, TG, LDL-C, HDL-C, APOA1, and APOB. These alterations in serum lipid profiles are associated with immune dysfunction and disease progression in HBV-ACLF. Notably, APOA1 and APOB serve as protective factors against 90-day mortality in hospitalized ACLF patients. Further investigation is warranted to elucidate the relationship between lipid metabolism disturbances and peripheral immunity in ACLF.
本研究旨在阐明慢性肝衰竭急性发作（ACLF）患者血脂异常、免疫功能和临床结局之间的相关性，特别强调脂质代谢和细胞免疫参数在乙型肝炎病毒相关ACLF（HBV-ACLF）中的临床意义。
对2014年1月至2024年1月在上海公共卫生临床中心收治的803例HBV-ACLF患者进行回顾性分析。根据临床结局将患者分为死亡组（n = 414）和存活组（n = 389）。收集临床基线数据、脂质代谢指标和细胞免疫参数。采用Spearman相关系数评估脂质代谢指标与细胞免疫参数之间的相关性，并应用多因素Cox比例风险模型分析死亡危险因素。
与存活组相比，死亡组的脂质代谢指标显著降低（P < 0.05）。包括高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白A1（APOA1）、载脂蛋白B（APOB）、总胆固醇（TC）和甘油三酯（TG）在内的脂质代谢指标与肝衰竭严重程度呈显著负相关（P < 0.05）。与淋巴细胞亚群计数的相关性分析显示，低密度脂蛋白、TG、TC、APOB与CD3⁺T细胞、CD4⁺T细胞、CD8⁺T细胞和CD45⁺T细胞呈正相关（P < 0.05）。APOA1和HDL-C与B细胞和NK细胞呈正相关（P < 0.05）。TG和APOB与CD4/CD8比值呈显著负相关（P < 0.05）。多因素Cox分析确定年龄、肌酐、总胆红素、国际标准化比值（INR）、肝性脑病和肝肾综合征是影响HBV-ACLF短期预后的独立危险因素，而钠、APOA1和APOB被确定为ACLF的独立保护因素（HR = 0.984，95%CI：0.974 - 0.995，P < 0.001，HR = 0.267，95%CI：0.120 - 0.596，P = 0.001，HR = 0.486，95%CI：0.282 - 0.838，P = 0.010）。
HBV-ACLF患者的TC、TG、LDL-C、HDL-C、APOA1和APOB水平降低。这些血清脂质谱的改变与HBV-ACLF中的免疫功能障碍和疾病进展相关。值得注意的是，APOA1和APOB是住院ACLF患者90天死亡率的保护因素。有必要进一步研究以阐明ACLF中脂质代谢紊乱与外周免疫之间的关系。
