血清肌酐与胱抑素C比值(CCR)对HBV相关慢加急性肝衰竭预后的评估价值
DOI: 10.12449/JCH240208
Value of serum creatinine-to-cystatin C ratio in assessing the prognosis of hepatitis B virus-related acute-on-chronic liver failure
-
摘要:
目的 探讨血清肌酐与胱抑素C比值(CCR)评估HBV相关慢加急性肝衰竭(HBV-ACLF)预后的临床价值。 方法 回顾性分析2021年1月—2022年11月苏州大学附属第一医院感染病科住院治疗的130例HBV-ACLF患者(治疗组)临床资料,根据治疗结局分为生存组(n=87)和死亡组(n=43);根据是否合并感染,分为感染组(n=37)和非感染组(n=93)。以同期30例健康体检者作为对照组。收集入院当天血常规指标,包括白细胞、血小板、中性粒细胞和淋巴细胞计数;观察入院当天、住院第5天、第10天、第15天血清肌酐、胱抑素C、血清Alb、PT,计算CCR、中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)、营养指数(PNI)、CCR5(入院后第5天CCR)、ΔCCR5(入院后第5天CCR-入院当天CCR)、CCR10(入院后第10天CCR)、ΔCCR10(入院后第10天CCR-入院后第5天CCR)、CCR15(入院后第15天CCR)、ΔCCR15(入院后第15天CCR-入院后第10天CCR),比较生存组和死亡组、感染组与非感染组上述指标的差异。计量资料两组间比较采用Mann-Whitney U检验;多组间比较采用Kruskal-Wallis H检验。单因素和多因素Logistic回归分析探讨影响疾病预后的因素;受试者工作特征曲线(ROC曲线)评估CCR对HBV-ACLF死亡事件的预测价值,ROC曲线下面积(AUC)比较采用DeLong检验。 结果 治疗组基线CCR、NLR、PNI、PT和Alb与健康对照组比较,差异均有统计学意义(P值均<0.001)。生存组与死亡组患者入院当天CCR、NLR、PT比较,差异均有统计学意义(P值均<0.05)。在130例HBV-ACLF患者中,有25例处于前期,48例处于早期,32例处于中期,25例处于晚期。各分期HBV-ACLF患者基线CCR、PLR及PT比较,差异均有统计学意义(P值均<0.05)。感染组与非感染组患者基线ΔCCR5、NLR比较,差异均有统计学意义(P值均<0.05)。患者入院第5天、第10天、第15天生存组与死亡组ΔCCR5、CCR10、CCR15比较,差异均有统计学意义(P值均<0.05)。多因素Logistic回归分析发现ΔCCR5(OR=1.175,95%CI:1.098~1.256,P<0.001)、NLR(OR=0.921,95%CI:0.880~0.964,P<0.001)和PT(OR=0.921,95%CI:0.873~0.973,P=0.003)是HBV-ACLF患者预后的独立影响因素。ΔCCR5的AUC为0.774,敏感度为0.687,特异度为0.757;ΔCCR5+PT+NLR联合的AUC为0.824,高于ΔCCR5、NLR、PT单独预测时的AUC(P值均<0.05)。 结论 ΔCCR5、NLR、PT可反映HBV-ACLF患者的病情及预后,是HBV-ACLF患者死亡事件的独立预测指标,ΔCCR5+PT+NLR联合时预测效能最佳。 -
关键词:
- 乙型肝炎病毒 /
- 慢加急性肝功能衰竭 /
- 肌酸酐 /
- 半胱氨酸蛋白酶抑制物C /
- 预后
Abstract:Objective To investigate the clinical value of serum creatinine-to-cystatin C ratio (CCR) in evaluating the prognosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods A retrospective analysis was performed for the clinical data of 130 patients with HBV-ACLF (treatment group) who were hospitalized in Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, from January 2021 to November 2022. According to the treatment outcome, they were divided into survival group with 87 patients and death group with 43 patients; according to the presence or absence of infection, they were divided into infection group with 37 patients and non-infection group with 93 patients. A total of 30 individuals who underwent physical examination during the same period of time were enrolled as control group. Routine blood test results were collected on the day of admission, including white blood cell count, platelet count, neutrophil count, and lymphocyte count; serum creatinine, cystatin C, serum albumin (Alb), and prothrombin time (PT) were observed on the day of admission and on days 5, 10, and 15 of hospitalization, and related indicators were calculated, including CCR, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), CCR5 (CCR on day 5 after admission), ΔCCR5 (CCR on day 5 after admission minus CCR on the day of admission), CCR10 (CCR on day 10 after admission), ΔCCR10 (CCR on day 10 after admission minus CCR on day 5 after admission), CCR15 (CCR on day 15 after admission), and ΔCCR15 (CCR on day 15 after admission minus CCR on day 10 after admission). The above indicators were compared between the survival group and the death group and between the infection group and the non-infection group. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. The univariate and multivariate logistic regression analyses were used to investigate the influencing factors for disease prognosis; the receiver operating characteristic (ROC) curve was used to assess the value of CCR in predicting HBV-ACLF death events, and the DeLong test was used for comparison of the area under the ROC curve (AUC). Results There were significant differences in CCR, NLR, PNI, PT, and Alb at baseline between the treatment group and the healthy control group (all P<0.001), and there were significant differences in CCR, NLR, and PT between the survival group and the death group on the day of admission (all P<0.05). Among the 130 patients with HBV-ACLF, there were 25 in the precancerous stage, 48 in the early stage, 32 in the intermediate stage, and 25 in the advanced stage, and there were significant differences in baseline CCR, PLR, and PT between the patients in different stages of HBV-ACLF (all P<0.05). There were significant differences in ΔCCR5 and NLR between the infection group and the non-infection group (P<0.05), and there were significant differences in ΔCCR5, CCR10, and CCR15 between the survival group and the death group (all P<0.05). The multivariate logistic regression analysis showed that ΔCCR5 (odds ratio [OR]=1.175, 95% confidence interval [CI]: 1.098 — 1.256, P<0.001), NLR (OR=0.921, 95%CI: 0.880 — 0.964, P<0.001), and PT (OR=0.921, 95%CI: 0.873 — 0.973, P=0.003) were independent influencing factors for the prognosis of HBV-ACLF patients. ΔCCR5 had an AUC of 0.774, a sensitivity of 0.687, and a specificity of 0.757, and the AUC of ΔCCR5+PT+NLR was 0.824, which was significantly higher than the AUC of ΔCCR5, NLR, or PT alone (all P<0.05). Conclusion ΔCCR5, NLR, and PT can reflect the condition and prognosis of patients with HBV-ACLF and are independent predictive indicators for death events in patients with HBV-ACLF. The combination ofΔCCR5, PT, and NLR has the best predictive efficiency. -
Key words:
- Hepatitis B Virus /
- Acute-On-Chronic Liver Failure /
- Creatinine /
- Cystatin C /
- Prognosis
-
HBV相关慢加急性肝衰竭(HBV-ACLF)是慢性乙型肝炎急性加重引起的危重症,常伴有多器官功能衰竭,病情进展迅速,死亡率高。HBV-ACLF会导致肝脏吸收、合成蛋白质和脂肪等营养物质功能明显下降,其营养不良发生率可达50%~90%,是影响终末期肝病患者存活率的独立预测因素[1]。HBV-ACLF所致营养不良常表现为肌肉减少症[2]。肌肉减少症定义为患者第三腰椎(L3)水平骨骼肌指数<38 cm2/m2(女性)或<42 cm2/m2(男性)[3],有研究[4]表明肌肉减少症与HBV-ACLF患者预后密切相关。肌肉减少症整体概念包括功能受损(肌肉力量低)和结构损伤(肌肉质量低)[5],低肌肉质量是肌肉减少症和营养不良的关键[6]。因此,对肌肉质量的评估是决定HBV-ACLF患者预后的关键因素。目前,肌肉质量检测有多种方式,例如磁共振成像、计算机断层扫描、双能X线吸收测定法和生物电阻抗方式等,金标准是应用腹部CT扫描患者L3水平层面的总骨骼肌估算肌肉质量。然而,有关肌肉质量的截断值存在争议和可变性[5]。因此,对肌肉质量的精确诊断依然具有挑战性,并且CT、磁共振成像、双能X线吸收测定法及生物电阻抗方式等诊断方法昂贵、耗时,对HBV-ACLF患者而言,可操作性小。近期一种新的肌肉质量的替代标志物[7],即血清肌酐与胱抑素C比值(serum creatinine to cystatin-C ratio,CCR)已被广泛报道并且用于预测神经危重症患者及癌症患者预后[8-9]。本研究旨在探讨CCR对HBV-ACLF患者预后的评估价值,以期为临床医生提供快速、可及、准确的预测信息。
1. 资料与方法
1.1 研究对象
选取2021年1月—2022年11月本院感染科住院治疗的HBV-ACLF患者130例纳入治疗组。ACLF的诊断符合《肝衰竭诊治指南(2018年版)》[10]中的诊断标准;HBV-ACLF纳入标准为符合ACLF诊断标准且HBsAg阳性者。排除标准:(1)合并其他引起肝衰竭的病因,如其他肝炎病毒感染、酒精性肝病、药物性肝病、自身免疫性肝病等;(2)HIV感染;(3)合并恶性肿瘤;(4)有肝移植史;(5)有严重的心脏、肾脏及肺部基础疾病。另选取同期30例健康体检者作为对照组。
1.2 研究方法
收集入院当天血常规指标,包括WBC、PLT、中性粒细胞和淋巴细胞计数;记录入院当天,住院第5天、第10天、第15天血清肌酐、胱抑素C、血清Alb、PT,计算CCR、中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)、营养指数(PNI)、CCR5(入院后第5天CCR)、ΔCCR5(入院后第5天CCR-入院当天CCR)、CCR10(入院后第10天CCR)、ΔCCR10(入院后第10天CCR-入院后第5天CCR),并通过类推计算CCR15和ΔCCR15。血常规采用SYSMEXXN系列全自动血常规分析仪检测;生化指标采用西门子ADVIA2400生物化学分析仪检测。血常规和生化指标检测均由本院检验科完成。
1.3 统计学方法
采用SPSS 25.0和Med-Calc 20.0软件进行统计分析。非正态分布的计量资料以M(P25~P75)表示,两组间比较采用Mann-Whitney U检验;多组间比较采用Kruskal-Wallis H检验。通过单因素和多因素Logistic回归分析患者预后的影响因素。绘制受试者工作特征曲线(ROC曲线)评估CCR对HBV-ACLF患者预后的预测价值,ROC曲线下面积(AUC)比较采用DeLong检验。P<0.05为差异有统计学意义。
2. 结果
2.1 一般资料
130例治疗组患者中,男78例,女52例,年龄21~83岁,平均53(42~66)岁;健康对照组中男15例,女15例,年龄40~74岁,平均52(47~76)岁。两组间年龄、性别比差异无统计学意义(P值均>0.05);治疗组基线CCR、NLR、PNI、PT和Alb与健康对照组比较,差异均有统计学意义(P值均<0.001)(表1)。
表 1 治疗组与健康对照组基线指标比较Table 1. Comparison of baseline indexes between the treatment group and the healthy control group指标 健康对照组(n=30) 治疗组(n=130) Z值 P值 男/女(例) 15/15 78/52 χ2=-1.233 0.190 年龄(岁) 52(47~76) 53(42~66) Z=-0.638 0.524 CCR(μmol/mg) 74.67(64.54~83.18) 51.22(43.35~62.33) Z=-6.378 <0.001 NLR 1.88(1.35~2.24) 5.81(2.89~11.11) Z=-6.745 <0.001 PLR 109.00(88.54~123.89) 96.77(57.38~146.99) Z=-1.437 0.151 PNI 51.80(49.34~54.80) 34.50(30.70~38.10) Z=-8.418 <0.001 PT(s) 10.90(10.38~11.75) 19.70(17.60~25.80) Z=-8.881 <0.001 Alb(g/L) 42.90(41.08~44.30) 29.10(26.53~32.60) Z=-8.746 <0.001 2.2 生存组与死亡组患者基线指标比较
根据治疗结局,将130例HBV-ACLF患者分为生存组(n=87)和死亡组(n=43)。结果显示,入院当天死亡组患者CCR、PT及NLR明显高于生存组(P值均<0.05)(图1)。
2.3 HBV-ACLF不同分期基线指标比较
在130例HBV-ACLF患者中,有25例处于前期,48例处于早期,32例处于中期,25例处于晚期。各分期HBV-ACLF患者基线CCR、PLR及PT比较,差异均有统计学意义(P值均<0.05)(表2)。
表 2 HBV-ACLF患者不同分期基线指标比较Table 2. Baseline markers of HBV-ACLF at different stages were compared指标 前期(n=25) 早期(n=48) 中期(n=32) 晚期(n=25) H值 P值 CCR(μmol/mg) 43.85(38.01~53.55) 53.01(43.18~64) 51.69(44.95~60.57) 56.84(46.43~80.44) 19.816 <0.001 NLR 5.70(2.38~10.69) 6.58(3.43~12.38) 5.55(2.80~10.45) 7.64(2.77~11.25) 2.070 0.558 PLR 77.38(52.27~140.63) 106.96(65.79~188.73) 69.44(50.18~143.86) 78.21(54.02~120.69) 13.698 0.003 PNI 32.65(30.60~37.25) 34.55(30.50~38.85) 33.90(29.35~37.65) 36.25(32.35~39.55) 5.949 0.114 PT(s) 17.60(16.25~19.05) 18.20(16.20~19.50) 24.00(22.50~26.05) 33.10(30.30~41.00) 187.731 <0.001 Alb(g/L) 28.70(26.20~30.50) 28.80(26.40~32.70) 29.10(26.10~32.90) 29.80(28.00~33.20) 3.285 0.350 2.4 HBV-ACLF合并感染与非感染者基线指标比较
根据是否合并感染,将130例HBV-ACLF患者分为感染组和非感染组,其中合并感染者37例。结果显示,感染组与非感染组基线ΔCCR5、NLR比较,差异均有统计学意义(P值均<0.05)(表3)。
表 3 非感染组与感染组基线指标比较Table 3. Comparison of baseline indexes between infected group and non-infected group指标 感染组(n=37) 非感染组(n=93) Z值 P值 CCR(μmol/mg) 54.17(40.49~66.08) 50.74(43.78~62.33) -1.098 0.272 NLR 12.38(7.64~16.29) 4.65(2.70~7.98) -6.363 <0.001 PLR 107.53(57.86~168.42) 93.18(60.34~145.16) -0.414 0.679 PNI 35.65(31.20~38.65) 34.20(30.50~37.80) -0.630 0.529 PT(s) 18.60(16.60~24.75) 20.30(17.50~25.10) -0.623 0.533 Alb(g/L) 28.70(25.25~32.40) 29.10(26.70~32.30) -0.416 0.678 ΔCCR5(μmol/mg) -13.94(-22.19~-5.48) -9.41(-13.40~-5.04) -2.675 0.007 2.5 死亡组与生存组患者入院第5天、第10天、第15天CCR动态比较
生存组与死亡组ΔCCR5、CCR10、CCR15比较,差异均有统计学意(P值均<0.05);两组CCR5、ΔCCR10、ΔCCR15比较,差异均无统计学意义(P值均>0.05)(表4)。
表 4 死亡组与生存组患者入院第5天、第10天、第15天CCR动态比较Table 4. Dynamic comparison of CCR in death group and survival group at 5、10 and 15 days after admission指标 死亡组(n=43) 生存组(n=87) Z值 P值 CCR5(μmol/mg) 39.70(32.32~46.86) 40.80(37.00~49.37) -0.360 0.719 ΔCCR5(μmol/mg) -18.43(-70.19~-13.40) -9.41(-11.25~-3.49) -5.380 <0.001 CCR10(μmol/mg) 40.00(1.82~44.62) 39.32(33.65~49.04) -2.410 0.016 ΔCCR10(μmol/mg) -4.89(-32.44~-0.69) -3.44(-5.56~1.47) -1.674 0.094 CCR15(μmol/mg) 27.84(24.69~34.43) 37.60(31.64~46.86) -3.480 <0.001 ΔCCR15(μmol/mg) -7.55(-12.16~22.87) -2.64(-7.49~2.09) -1.323 0.186 2.6 HBV-ACLF患者预后相关因素分析
将患者基线指标进行二分类单因素Logistic回归分析,结果显示,CCR、NLR、PT和ΔCCR5是HBV-ACLF死亡的预测因子(P值均<0.05)。将这4项指标行多因素Logistic回归分析,结果显示,ΔCCR5(OR=1.175)、NLR(OR=0.921)和PT(OR=0.921)是HBV-ACLF患者预后的独立影响因素(P值均<0.05)(表5)。将死亡作为阳性事件绘制ROC曲线(表6,图2),结果显示,ΔCCR5+PT+NLR联合预测的AUC高于三者单独预测的AUC(Z值分别为3.525、4.155、2.065,P值分别为<0.001、<0.001、0.039)。
表 5 基线指标单因素及多因素Logistic回归分析Table 5. The baseline indexes were analyzed by binary single factor and multivariate Logistic regression指标 单因素分析 多因素分析 OR(95%CI) P值 OR(95%CI) P值 ΔCCR5(μmol/mg) 1.163(1.101~1.228) <0.001 1.175(1.098~1.256) <0.001 PT(s) 0.912(0.876~0.950) <0.001 0.921(0.873~0.973) 0.003 NLR 0.948(0.917~0.980) 0.001 0.921(0.880~0.964) <0.001 CCR(μmol/mg) 0.959(0.943~0.976) <0.001 1.006(0.976~1.036) 0.713 PLR 1.003(0.999~1.007) 0.191 PNI 0.997(0.976~1.018) 0.780 Alb(g/L) 0.993(0.937~1.051) 0.798 表 6 ΔCCR5、PT、NLR、ΔCCR5+PT+NLR预测HBV-ACLF患者死亡事件效能分析Table 6. Efficacy analysis of ΔCCR5, PT, NLR, ΔCCR5+PT+NLR in predicting death events in patients with HBV-ACLF变量 AUC 95%CI P值 最佳临界值 敏感度 特异度 约登指数 PT(s) 0.704 0.643~0.761 <0.001 21.500 0.710 0.650 0.360 NLR 0.645 0.581~0.705 <0.001 4.610 0.481 0.762 0.244 ∆CCR5(μmol/mg) 0.774 0.712~0.828 <0.001 -10.150 0.687 0.757 0.444 ∆CCR5+PT+NLR 0.824 0.767~0.873 <0.001 0.700 0.680 0.833 0.513 3. 讨论
终末期肝病模型、Child-Turcotte-Pugh、COSSH-ACLF[11]、Nomogram[12]、P8评分[13]等是预测肝衰竭患者病死率的有效工具,但常规的预后评分系统不能有效评估肝衰竭患者的营养和功能状况,且计算繁琐不易获取。大量采用不同方法量化肌肉质量的横断面和纵向研究[14-16]表明,肌肉质量已成为临床中慢性肝病患者重要的结局预测指标。此外,肝衰竭患者并发感染的风险较高[17],故在本研究中,纳入了炎症相关指标NLR和PLR。目前常用于肝衰竭营养状态的评价指标包括:膳食调查、主观全面评价法(SGA)、人体测量学检查、营养风险筛查(NRS-2002)、人体成分分析、生化指标检查(肌酐身高指数、淋巴细胞总数、氮平衡总数)等[1,18],但存在数据收集不精确、评估繁琐等缺点,故临床实用性不强。肌肉减少症系分解代谢的最终产物,Haines等[19]认为尿素/肌酐比(UCR)为危重病相关分解代谢的标志物,由于分解代谢会增加尿素生成,而肌肉质量的逐渐丧失导致肌酐生成减少,因此,UCR升高可能是持续分解代谢的合理预测指标。尽管UCR在未来的研究中具有潜在的作用,但临床可用性有限,因为尿素是活性蛋白水解的产物,低UCR未必可以排除低肌肉质量。其次,利尿剂、高膳食氨基酸含量和消化道出血等多种因素引起的有效血容量减少会导致UCR升高,急性肾损伤也可能会改变UCR,这些均与分解代谢无关[19]。故UCR是否可以作为肌肉质量下降的标志物仍需证实。关于分解代谢的新型标志物生长/分化因子-15(GDF-15)[20],其既是一种应激诱导的细胞因子,在不同的身体部位具有不同的作用,又是一种与细胞衰老和凋亡相关的细胞自主调节剂[21],与疾病状态及病死率增加有关[22]。尽管有证据[20,23]表明GDF-15与营养和线粒体应激有关,但迄今为止并无证据表明其作为分解代谢潜在标志物的确切作用。
近期,Kashani等[7]提出以CCR作为肌肉质量的替代标志物。肌酐和胱抑素C是临床应用中肾小球滤过率和肾功能的通用标志物。肌酐是一种来源于骨骼肌的物质,目前被认为是反映肌肉质量的可靠血液参数[24]。但是,肌酐水平依赖于肾功能[25],因此限制了其预测肌肉质量的可靠性。胱抑素C是一种低分子量蛋白,且在所有有核细胞中均能以恒定的速度繁殖,同时胱抑素C无肾小管分泌,其血清浓度主要取决于肾小球滤过率,故胱抑素C水平通常不受年龄、性别、饮食和肌肉质量等肾外因素的影响[8,25],被认为是更可靠的功能标志物。CCR自Kashani等[7]首次提出以来,已被报道与诸多疾病的进展及预后密切相关[26-28]。有研究[26]表明,CCR可以预测关节置换手术后老年髋部骨折患者的肺炎。Kashani等[7]研究显示,CCR是评估ICU患者肌肉质量的一个公平衡量标准,可以预测初始无急性肾损伤住院患者90天病死率。CCR在癌症患者中亦可作为一种可靠的肌肉质量标志物,评估癌症患者预后[28-29]。本研究动态观察了HBV-ACLF患者入院时和治疗第5天、第10天、第15天的CCR,单因素Logistic回归分析表明ΔCCR5、CCR、PT、NLR是HBV-ACLF死亡的预测因子;多因素Logistic回归分析结果显示,ΔCCR5、PT、NLR是HBV-ACLF死亡事件的独立预测因子;ROC曲线分析发现,ΔCCR5+PT+NLR联合时其AUC高于任意单项指标,表明联合时预测效能最佳。
综上所述,HBV-ACLF是一种进展快速且伴有高病死率的疾病,普遍存在进行性肌肉消耗及营养不良。动态监测肌肉质量的替代标志物CCR可以反映患者营养状况,评估患者死亡风险,与常规的预后评分系统相比,CCR在临床实践中具有较强的可操作性,简单易行,值得推广应用。本研究也存在一些局限性,如样本量较少,且为回顾性研究,未来需进一步扩大样本,开展多中心前瞻性研究。
-
表 1 治疗组与健康对照组基线指标比较
Table 1. Comparison of baseline indexes between the treatment group and the healthy control group
指标 健康对照组(n=30) 治疗组(n=130) Z值 P值 男/女(例) 15/15 78/52 χ2=-1.233 0.190 年龄(岁) 52(47~76) 53(42~66) Z=-0.638 0.524 CCR(μmol/mg) 74.67(64.54~83.18) 51.22(43.35~62.33) Z=-6.378 <0.001 NLR 1.88(1.35~2.24) 5.81(2.89~11.11) Z=-6.745 <0.001 PLR 109.00(88.54~123.89) 96.77(57.38~146.99) Z=-1.437 0.151 PNI 51.80(49.34~54.80) 34.50(30.70~38.10) Z=-8.418 <0.001 PT(s) 10.90(10.38~11.75) 19.70(17.60~25.80) Z=-8.881 <0.001 Alb(g/L) 42.90(41.08~44.30) 29.10(26.53~32.60) Z=-8.746 <0.001 表 2 HBV-ACLF患者不同分期基线指标比较
Table 2. Baseline markers of HBV-ACLF at different stages were compared
指标 前期(n=25) 早期(n=48) 中期(n=32) 晚期(n=25) H值 P值 CCR(μmol/mg) 43.85(38.01~53.55) 53.01(43.18~64) 51.69(44.95~60.57) 56.84(46.43~80.44) 19.816 <0.001 NLR 5.70(2.38~10.69) 6.58(3.43~12.38) 5.55(2.80~10.45) 7.64(2.77~11.25) 2.070 0.558 PLR 77.38(52.27~140.63) 106.96(65.79~188.73) 69.44(50.18~143.86) 78.21(54.02~120.69) 13.698 0.003 PNI 32.65(30.60~37.25) 34.55(30.50~38.85) 33.90(29.35~37.65) 36.25(32.35~39.55) 5.949 0.114 PT(s) 17.60(16.25~19.05) 18.20(16.20~19.50) 24.00(22.50~26.05) 33.10(30.30~41.00) 187.731 <0.001 Alb(g/L) 28.70(26.20~30.50) 28.80(26.40~32.70) 29.10(26.10~32.90) 29.80(28.00~33.20) 3.285 0.350 表 3 非感染组与感染组基线指标比较
Table 3. Comparison of baseline indexes between infected group and non-infected group
指标 感染组(n=37) 非感染组(n=93) Z值 P值 CCR(μmol/mg) 54.17(40.49~66.08) 50.74(43.78~62.33) -1.098 0.272 NLR 12.38(7.64~16.29) 4.65(2.70~7.98) -6.363 <0.001 PLR 107.53(57.86~168.42) 93.18(60.34~145.16) -0.414 0.679 PNI 35.65(31.20~38.65) 34.20(30.50~37.80) -0.630 0.529 PT(s) 18.60(16.60~24.75) 20.30(17.50~25.10) -0.623 0.533 Alb(g/L) 28.70(25.25~32.40) 29.10(26.70~32.30) -0.416 0.678 ΔCCR5(μmol/mg) -13.94(-22.19~-5.48) -9.41(-13.40~-5.04) -2.675 0.007 表 4 死亡组与生存组患者入院第5天、第10天、第15天CCR动态比较
Table 4. Dynamic comparison of CCR in death group and survival group at 5、10 and 15 days after admission
指标 死亡组(n=43) 生存组(n=87) Z值 P值 CCR5(μmol/mg) 39.70(32.32~46.86) 40.80(37.00~49.37) -0.360 0.719 ΔCCR5(μmol/mg) -18.43(-70.19~-13.40) -9.41(-11.25~-3.49) -5.380 <0.001 CCR10(μmol/mg) 40.00(1.82~44.62) 39.32(33.65~49.04) -2.410 0.016 ΔCCR10(μmol/mg) -4.89(-32.44~-0.69) -3.44(-5.56~1.47) -1.674 0.094 CCR15(μmol/mg) 27.84(24.69~34.43) 37.60(31.64~46.86) -3.480 <0.001 ΔCCR15(μmol/mg) -7.55(-12.16~22.87) -2.64(-7.49~2.09) -1.323 0.186 表 5 基线指标单因素及多因素Logistic回归分析
Table 5. The baseline indexes were analyzed by binary single factor and multivariate Logistic regression
指标 单因素分析 多因素分析 OR(95%CI) P值 OR(95%CI) P值 ΔCCR5(μmol/mg) 1.163(1.101~1.228) <0.001 1.175(1.098~1.256) <0.001 PT(s) 0.912(0.876~0.950) <0.001 0.921(0.873~0.973) 0.003 NLR 0.948(0.917~0.980) 0.001 0.921(0.880~0.964) <0.001 CCR(μmol/mg) 0.959(0.943~0.976) <0.001 1.006(0.976~1.036) 0.713 PLR 1.003(0.999~1.007) 0.191 PNI 0.997(0.976~1.018) 0.780 Alb(g/L) 0.993(0.937~1.051) 0.798 表 6 ΔCCR5、PT、NLR、ΔCCR5+PT+NLR预测HBV-ACLF患者死亡事件效能分析
Table 6. Efficacy analysis of ΔCCR5, PT, NLR, ΔCCR5+PT+NLR in predicting death events in patients with HBV-ACLF
变量 AUC 95%CI P值 最佳临界值 敏感度 特异度 约登指数 PT(s) 0.704 0.643~0.761 <0.001 21.500 0.710 0.650 0.360 NLR 0.645 0.581~0.705 <0.001 4.610 0.481 0.762 0.244 ∆CCR5(μmol/mg) 0.774 0.712~0.828 <0.001 -10.150 0.687 0.757 0.444 ∆CCR5+PT+NLR 0.824 0.767~0.873 <0.001 0.700 0.680 0.833 0.513 -
[1] Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Gastroenterology, Chinese Medical Association. Clinical guidelines on nutrition in end-stage liver disease[J]. J Clin Hepatol, 2019, 35( 6): 1222- 1230. DOI: 10.3969/j.issn.1001-5256.2019.06.010.中华医学会肝病学分会, 中华医学会消化病学分会. 终末期肝病临床营养指南[J]. 临床肝胆病杂志, 2019, 35( 6): 1222- 1230. DOI: 10.3969/j.issn.1001-5256.2019.06.010. [2] MANGANA DEL RIO T, SACLEUX SC, VIONNET J, et al. Body composition and short-term mortality in patients critically ill with acute-on-chronic liver failure[J]. JHEP Rep, 2023, 5( 8): 100758. DOI: 10.1016/j.jhepr.2023.100758. [3] NISHIKAWA H, SHIRAKI M, HIRAMATSU A, et al. Japan Society of Hepatology guidelines for sarcopenia in liver disease(1st edition): Recommendation from the working group for creation of sarcopenia assessment criteria[J]. Hepatol Res, 2016, 46( 10): 951- 963. DOI: 10.1111/hepr.12774. [4] PENG H, ZHANG Q, LUO L, et al. A prognostic model of acute-on-chronic liver failure based on sarcopenia[J]. Hepatol Int, 2022, 16( 4): 964- 972. DOI: 10.1007/s12072-022-10363-2. [5] SANCHEZ-RODRIGUEZ D, MARCO E, CRUZ-JENTOFT AJ. Defining sarcopenia: Some caveats and challenges[J]. Curr Opin Clin Nutr Metab Care, 2020, 23( 2): 127- 132. DOI: 10.1097/MCO.0000000000000621. [6] SAYER AA, CRUZ-JENTOFT A. Sarcopenia definition, diagnosis and treatment: Consensus is growing[J]. Age Ageing, 2022, 51( 10): afac220. DOI: 10.1093/ageing/afac220. [7] KASHANI KB, FRAZEE EN, KUKRÁLOVÁ L, et al. Evaluating muscle mass by using markers of kidney function: Development of the sarcopenia index[J]. Crit Care Med, 2017, 45( 1): e23- e29. DOI: 10.1097/CCM.0000000000002013. [8] WANG S, XIE L, XU J, et al. Predictive value of serum creatinine/cystatin C in neurocritically ill patients[J]. Brain Behav, 2019, 9( 12): e01462. DOI: 10.1002/brb3.1462. [9] JUNG CY, KIM HW, HAN SH, et al. Creatinine-cystatin C ratio and mortality in cancer patients: A retrospective cohort study[J]. J Cachexia Sarcopenia Muscle, 2022, 13( 4): 2064- 2072. DOI: 10.1002/jcsm.13006. [10] Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2018)[J]. J Clin Hepatol, 2019, 35( 1): 38- 44. DOI: 10.3969/j.issn.1001-5256.2019.01.007.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(2018年版)[J]. 临床肝胆病杂志, 2019, 35( 1): 38- 44. DOI: 10.3969/j.issn.1001-5256.2019.01.007. [11] 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. [12] GAO FY, ZHANG QQ, LIU Y, et al. Nomogram prediction of individual prognosis of patients with acute-on-chronic hepatitis B liver failure[J]. Dig Liver Dis, 2019, 51( 3): 425- 433. DOI: 10.1016/j.dld.2018.08.023. [13] SUN ZY, LIU XL, WU DX, et al. Circulating proteomic panels for diagnosis and risk stratification of acute-on-chronic liver failure in patients with viral hepatitis B[J]. Theranostics, 2019, 9( 4): 1200- 1214. DOI: 10.7150/thno.31991. [14] BEER L, BASTATI N, BA-SSALAMAH A, et al. MRI-defined sarcopenia predicts mortality in patients with chronic liver disease[J]. Liver Int, 2020, 40( 11): 2797- 2807. DOI: 10.1111/liv.14648. [15] JIN L, LI X. MRI-defined sarcopenia predicts mortality in patients with chronic liver disease[J]. Liver Int, 2021, 41( 1): 223. DOI: 10.1111/liv.14691. [16] WANG T, ZHANG YG, LI QQ, et al. Evaluation value of area index of the third lumbar psoas major muscle in nutritional status and prognosis of patients with cirrhosis[J]. Clin J Med Offic, 2022, 50( 7): 729- 732. DOI: 10.16680/j.1671-3826.2022.07.18.王然, 张永国, 李谦谦, 等. 第三腰椎腰大肌面积指数对肝硬化患者营养状态及预后评估价值[J]. 临床军医杂志, 2022, 50( 7): 729- 732. DOI: 10.16680/j.1671-3826.2022.07.18. [17] Society of Infectious Diseases, Chinese Medical Association. Expert consensus on diagnosis and treatment of end-stage liver disease complicated with infections(2021 version)[J]. J Clin Hepatol, 2022, 38( 2): 304- 310. DOI: 10.3969/j.issn.1001-5256.2022.02.010.中华医学会感染病学分会. 终末期肝病合并感染诊治专家共识(2021年版)[J]. 临床肝胆病杂志, 2022, 38( 2): 304- 310. DOI: 10.3969/j.issn.1001-5256.2022.02.010. [18] WANG XB, ZHANG Q, GAO FY. Prediction of acute-on-chronic liver failure and integrated traditional Chinese and Western medicine therapy[J]. J Clin Hepatol, 2020, 36( 1): 19- 25. DOI: 10.3969/j.issn.1001-5256.2020.01.003.王宪波, 张群, 高方媛. 慢加急性肝衰竭的预后评估及中西医结合治疗[J]. 临床肝胆病杂志, 2020, 36( 1): 19- 25. DOI: 10.3969/j.issn.1001-5256.2020.01.003. [19] HAINES RW, ZOLFAGHARI P, WAN Y, et al. Elevated urea-to-creatinine ratio provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma[J]. Intensive care medicine, 2019, 45( 12): 1718- 1731. DOI: 10.1007/s00134-019-05760-5. [20] PAGE A, FLOWER L, PROWLE J, et al. Novel methods to identify and measure catabolism[J]. Curr Opin Crit Care, 2021, 27( 4): 361- 366. DOI: 10.1097/MCC.0000000000000842. [21] VERHAMME FM, FREEMAN CM, BRUSSELLE GG, et al. GDF-15 in pulmonary and critical care medicine[J]. Am J Respir Cell Mol Biol, 2019, 60( 6): 621- 628. DOI: 10.1165/rcmb.2018-0379TR. [22] LEE ES, KIM SH, KIM HJ, et al. Growth differentiation factor 15 predicts chronic liver disease severity[J]. Gut Liver, 2017, 11( 2): 276- 282. DOI: 10.5009/gnl16049. [23] ZHANG IW, CURTO A, LÓPEZ-VICARIO C, et al. Mitochondrial dysfunction governs immunometabolism in leukocytes of patients with acute-on-chronic liver failure[J]. J Hepatol, 2022, 76( 1): 93- 106. DOI: 10.1016/j.jhep.2021.08.009. [24] WEINERT LS, CAMARGO EG, SOARES AA, et al. Glomerular filtration rate estimation: Performance of serum cystatin C-based prediction equations[J]. Clin Chem Lab Med, 2011, 49( 11): 1761- 1771. DOI: 10.1515/CCLM.2011.670. [25] EINHORN D, MENDE CW. Combining creatinine-based EGFR with cystatin C-based EGFR to better assess renal function in patients with diabetes and chronic kidney disease 3a: Implications for drug selection and dosage in type 2 diabetes[J]. Endocr Pract, 2015, 21( 11): 1301- 1302. DOI: 10.4158/EP15821.ED. [26] CHEN XY, SHEN YJ, HOU LS, et al. Sarcopenia index based on serum creatinine and cystatin C predicts the risk of postoperative complications following hip fracture surgery in older adults[J]. BMC Geriatr, 2021, 21( 1): 541. DOI: 10.1186/s12877-021-02522-1. [27] ULMANN G, KAÏ J, DURAND JP, et al. Creatinine-to-cystatin C ratio and bioelectrical impedance analysis for the assessement of low lean body mass in cancer patients: Comparison to L3-computed tomography scan[J]. Nutrition, 2021, 81: 110895. DOI: 10.1016/j.nut.2020.110895. [28] ZHENG C, WANG E, LI JS, et al. Serum creatinine/cystatin C ratio as a screening tool for sarcopenia and prognostic indicator for patients with esophageal cancer[J]. BMC Geriatr, 2022, 22( 1): 207. DOI: 10.1186/s12877-022-02925-8. [29] SUN J, YANG H, CAI WT, et al. Serum creatinine/cystatin C ratio as a surrogate marker for sarcopenia in patients with gastric cancer[J]. BMC Gastroenterol, 2022, 22( 1): 26. DOI: 10.1186/s12876-022-02093-4. 期刊类型引用(2)
1. 雷天香,张秋林,林少勤,张奡,郭维文,曾碧珊. 金锁固精丸加味治疗糖尿病肾病G3期临床研究. 河南中医. 2025(01): 92-97 . 百度学术
2. 徐政,张玉静,李宇航,刘苏来,吕媛. 成人急性肝衰竭患者预后影响因素Logistic回归分析. 湖南师范大学学报(医学版). 2024(05): 139-142+170 . 百度学术
其他类型引用(0)
-