乳酸水平对HBV相关慢加急性肝衰竭患者短期预后的预测价值
DOI: 10.3969/j.issn.1001-5256.2022.07.007
Value of lactate level in predicting the short-term prognosis of patients with acute-on-chronic hepatitis B liver failure
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摘要:
目的 本研究旨在评估乳酸对HBV相关慢加急性肝衰竭(HBV-ALCF)患者90 d预后的预测价值。 方法 回顾性纳入2017年1月—2021年6月新疆医科大学第一附属医院感染病·肝病中心收治的117例HBV-ACLF患者,根据90 d随访结果分为生存组(n=43)和死亡组(n=74);收集患者于本院诊断HBV-ACLF后24 h内的血常规、肝肾功能、凝血功能、动脉血气、肝性脑病等并发症,计算ALBI、MELD、MELD-Na、MESO、iMELD、CLIF-C ACLF评分。计量资料符合正态分布的组间比较采用t检验,非正态分布的组间比较采用Mann-Whitney U检验,计数资料组间比较采用χ2检验。采用二元logistic分析乳酸是否为HBV-ACLF患者90 d预后的独立危险因素,Pearson相关分析检验乳酸与感染情况及临床并发症的相关性。绘制受试者工作特征曲线(ROC曲线)分析乳酸相加于各评分后能否提高现有模型的预测价值,两两比较采用Z检验。 结果 死亡组WBC、INR、乳酸均大于生存组,Na小于生存组,差异均有统计学意义(Z值分别为-2.813、-2.855、-3.186、-2.044,P值均<0.05);年龄、MELD、MELD-Na、MESO、iMELD、CLIF-C ACLF评分均显著高于生存组,差异均有统计学意义(t值分别为2.536、4.615、4.247、4.941、5.832、7.562,P值均<0.05)。logistic分析表明年龄(OR=1.075,95%CI: 1.026~1.127,P=0.002)、INR(OR=2.198,95%CI: 1.149~4.203,P=0.017)、乳酸(OR=1.431,95%CI: 1.002~2.044,P=0.049)是HBV-ACLF患者90 d预后的独立危险因素,将乳酸纳入现有模型后ROC曲线下面积均有所增加。 结论 乳酸是HBV-ACLF患者90 d预后的独立危险因素,将其纳入现有模型可能提高预测价值。 Abstract:Objective To investigate the value of lactate in predicting the 90-day prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods A retrospective analysis was performed for 117 patients with HBV-ACLF who were admitted to Center for Infectious Diseases-Hepatology, The First Affiliated Hospital of Xinjiang Medical University, from January 2017 to June 2021, and according to the results of 90-day follow-up, they were divided into survival group with 43 patients and death group with 74 patients. Related clinical data were collected, including routine blood test results, hepatic and renal function, coagulation function, arterial blood gas parameters, and complications such as hepatic encephalopathy within 24 hours after the diagnosis of HBV-ACLF in our hospital, and albumin-bilirubin (ALBI), Model for End-Stage Liver Disease (MELD), MELD combined with serum sodium concentration (MELD-Na), MELD to SNa ratio (MESO), integrated MELD (iMELD), and CLIF-C ACLF scores were calculated. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A binary logistic regression analysis was used to investigate whether lactate was an independent risk factor for the 90-d prognosis of HBV-ACLF patients, and a Pearson correlation analysis was used to investigate the correlation of lactate with infection and clinical complications. The receiver operating characteristic (ROC) curve was plotted to analyze whether lactate, in combination with each score, can improve the predictive value of the existing model, and the Z test was used for pairwise comparison. Results Compared with the survival group, the death group had significantly higher white blood cell count, international normalized ratio (INR), and lactate and a significantly lower level of Na (Z=-2.813, -2.855, and -3.186, and -2.044, all P < 0.05), as well as significantly higher age and MELD, MELD-Na, MESO, iMELD, and CLIF-C ACLF scores (t=2.536, 4.615, 4.247, 4.941, 5.832, and 7.562, all P < 0.05). The logistic regression analysis showed that age (odds ratio [OR]=1.075, 95% confidence interval [CI]: 1.026-1.127, P=0.002), INR (OR=2.198, 95%CI: 1.149-4.203, P=0.017), and lactate (OR=1.431, 95%CI: 1.002-2.044, P=0.049) were independent risk factors for the 90-day prognosis of patients with HBV-ACLF, and there was an increase in the area under the ROC curve after lactate was included in the existing models. Conclusion Lactate is an independent risk factor for the 90-day prognosis of patients with HBV-ACLF, and its inclusion in existing models may improve predictive value. -
Key words:
- Acute-on-Chronic Liver Failure /
- Hepatitis B virus /
- Lactic Acid /
- Prognosis
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慢加急性肝衰竭(ACLF)是一种以慢性肝病为基础的急剧肝功能恶化、伴有肝或肝外器官衰竭的复杂综合征,短期病死率可达50%~90%[1]。HBV感染是亚太地区ACLF最常见的病因,该地区每年约有12万人死于HBV相关慢加急性肝衰竭(HBV-ALCF)[2-3]。肝功能障碍和多系统器官衰竭之间有1~2周的黄金治疗窗口期[4]。因此,在临床医生决定给予内科综合治疗或肝移植等措施之前,准确评估预后至关重要。目前临床上使用的大多数预后评分基于欧美人群建立,在HBV-ALCF患者中的应用仍有不足和限制。因此,需要一个简单易行的参数提高预测价值以指导治疗措施的选择。
乳酸是葡萄糖无氧代谢的最终产物,被广泛用作器官衰竭或严重细菌感染的重要指标[5]。机体70%的乳酸由肝脏代谢,经肾脏排出[6]。高乳酸血症通常反映了肝功能不全患者体内乳酸产生增加和清除功能受损[5]。大量动物实验和临床研究表明,乳酸在评估危重病患者病情发展和短期预后方面具有良好的性能,死亡风险随着乳酸水平的升高而增加[7]。本研究旨在评估乳酸在预测HBV-ACLF患者短期预后中的价值,以促进早期治疗,提高患者远期生存。
1. 资料与方法
1.1 研究对象
选取2017年1月—2021年6月在新疆医科大学第一附属医院感染病·肝病中心收治的HBV-ACLF患者,根据本院诊断HBV-ACLF之日起90 d的随访结果分为生存组和死亡组。纳入标准:(1)年龄在18~75岁,HBsAg阳性半年以上;(2)符合《肝衰竭诊治指南(2018年版)》[8]中ACLF的诊断标准,即慢性肝病基础上黄疸迅速加深,血清TBil≥10倍正常值上限或每日上升≥17.1 μmol/L,伴有出血表现、PTA≤40%(或INR≥1.5)。排除标准:(1)合并恶性肿瘤、血液系统疾病及其他严重影响生命的基础疾病;(2)自身免疫性、胆汁淤积性肝病;(3)酒精、药物等肝毒性物质导致的肝衰竭;(4)妊娠及哺乳期女性;(5)长期行抗凝药物治疗的患者;(6)患者随访资料不全或失访。
1.2 研究方法
1.2.1 观察指标
记录患者基本信息,如性别、年龄、住院天数,收集患者于本院诊断HBV-ACLF后24 h内的血常规、肝肾功能、凝血功能、动脉血气、血管活性药物使用情况、肝性脑病等并发症情况。
1.2.2 治疗方案
所有患者均予以内科综合治疗,包括卧床休息、核苷类抗病毒药物、高碳水化合物、适量蛋白饮食、低脂,应用护肝药物,补充白蛋白,输注血浆纠正凝血功能、内科治疗无效者行人工肝治疗、纠正电解质紊乱等。
1.2.3 六种评分系统
ALBI评分[9]:0.66×log10[TBil(μmol/L)]-0.085×[Alb(g/L)];MELD评分[10]:11.2×ln(INR)+9.6×ln[Cr(mg/dL)]+3.8×ln[TBil(mg/dL)]+ 6.4×病因(选取对象为HBV-ACLF,所以病因取1);MELD-Na评分[11]:MELD+1.59[135-Na(mmol/L)];MESO指数[12]:[MELD/Na(mmol/L)]×10;iMELD评分[13]:MELD+(0.3×年龄)-[0.7×Na(mmol/L)]+100;CLIF-C ACLF评分[14]:10×[0.33×CLIF-C OF评分(表 1)+0.04×年龄+0.63×Ln(WBC)-2]。
表 1 CLIF-C OF评分Table 1. CLIF-C OF scores器官/系统 1分 2分 3分 肝脏(TBil, mg/dL) <6 6~12 >12 肾脏(Cr, mg/dL) <2 2~3.4 ≥3.5或肾脏替代治疗 凝血功能(INR) <2 2~2.4 ≥2.5 神经(感性脑病分级) 0 Ⅰ~Ⅱ Ⅲ~Ⅳ 循环(平均动脉压,mmHg) ≥70 <70 应用血管活性药物
(去甲肾上腺素、多巴胺、肾上腺素)呼吸 PaO2/FiO2 >300 201~300 ≤200 SPO2/FiO2 >357 215~357 ≤214 注:Cr,肌酐;PaO2/FiO2,氧分压/氧浓度;SpO2/FiO2,血氧饱和度/氧浓度。 1.3 统计学方法
采用SPSS 23.0软件分析数据。符合正态分布的计量资料用x±s表示,组间比较采用t检验;非正态分布的用M(P25~P75)表示,组间比较采用Mann-Whitney U检验。计数资料组间比较采用χ2检验。logistic分析乳酸是否为HBV-ACLF患者短期预后的独立危险因素,乳酸与感染情况及临床并发症的相关性采用Pearson相关性分析。构建受试者工作特征曲线(ROC曲线),用曲线下面积(AUC)评价不同评分模型对HBV-ACLF患者的预测价值。当AUC>0.7时,该方法具有临床应用价值。进一步在Medcalc统计软件中对新旧评分的AUC进行两两比较,采用Z检验。P<0.05为差异有统计学意义。
2. 结果
2.1 一般资料
共收集201例HBV-ACLF住院患者,排除失访14例、肝移植2例、药物性肝损伤2例、恶性肿瘤20例、乳酸资料不全51例,最终纳入本研究117例。其中入院首日病例资料中报告动脉血乳酸93例(79.5%)、TBil 113例(96.6%)、INR 111例(94.9%)。根据90 d随访结果将HBV-ACLF患者分为生存组(n=43)和死亡组(n=74)。死亡组年龄、WBC、INR、乳酸、MELD、MELD-Na、MESO、iMELD、CLIF-C ACLF均显著高于生存组,Na小于生存组,差异均有统计学意义(P值均<0.05);两组之间糖尿病、肝硬化发生率差异均无统计学意义(P值均>0.05)(表 2)。死亡组发生肺部感染或感染性休克,合并上消化道出血、肝肾综合征、肝性脑病等并发症发生率明显高于生存组(P值均<0.05)(表 3)。
表 2 入组时基线资料的比较分析Table 2. Comparative analysis of baseline information at enrollment指标 生存组(n=43) 死亡组(n=74) 统计值 P值 年龄(岁) 44.05±10.32 49.70±12.33 t=2.536 0.013 男/女(例) 31/12 55/19 χ2=0.070 0.792 WBC(×109/L) 6.25(5.10~8.20) 7.83(5.90~11.57) Z=-2.813 0.005 红细胞分布宽度(%) 16.20(14.60~17.80) 17.45(15.28~18.60) Z=-1.804 0.071 Na(mmol/L) 135.00(132.42~136.87) 132.96(128.42~136.0) Z=-2.044 0.041 血小板压积(%) 0.56(0.31~0.90) 0.59(0.40~1.02) Z=-0.933 0.351 PLT(×109/L) 122(90~142) 91(60~133.5) Z=-1.883 0.060 Alb(g/L) 29.29(24.81~32.57) 28.22(25.54~31.42) Z=-0.334 0.739 INR 2.52(1.96~3.03) 2.85(2.43~3.59) Z=-2.855 0.004 Cr(mg/dL) 0.72(0.62~0.88) 0.84(0.62~1.16) Z=-1.916 0.055 TBil(mg/dL) 17.08(13.46~20.58) 19.67(14.12~26.51) Z=-1.713 0.087 AST(U/L) 222.72(111.14~563.52) 215.95(105.59~529.12) Z=-0.636 0.525 ALT(U/L) 362.10(161.57~682.10) 197.87(64.42~648.65) Z=-1.269 0.204 乳酸(mmol/L) 2.30(1.80~2.70) 2.60(2.00~3.82) Z=-3.186 0.001 ALBI评分 -1.30(-1.59~-0.94) -1.16(-1.48~-0.92) Z=-1.198 0.231 MELD评分 24.29±4.27 28.99±6.74 t=4.615 <0.001 MELD-Na评分 25.66±8.33 34.28±13.63 t=4.247 <0.001 MESO评分 1.81±0.34 2.21±0.53 t=4.941 <0.001 iMELD评分 43.61±5.69 51.73±9.37 t=5.832 <0.001 CLIF-C ACLF评分 45.48±6.71 56.70±9.22 t=7.562 <0.001 糖尿病[例(%)] 3(6.98) 14(18.92) χ2=3.123 0.077 肝硬化[例(%)] 25(58.14) 52(70.27) χ2=1.779 0.182 人工肝支持[例(%)] 26(60.47) 42(56.76) χ2=0.154 0.695 表 3 两组并发症发生情况比较Table 3. Comparison of the occurrence of complications between the two groups指标 例数 生存组(n=43) 死亡组(n=74) χ2值 P值 上消化道出血[例(%)] 15 1(2.33) 14(18.92) 6.700 0.010 肺部感染或感染性休克[例(%)] 41 8(18.60) 33(44.59) 8.070 0.004 肝肾综合征[例(%)] 13 0 13(17.57) 6.813 0.009 腹水[例(%)] 98 34(79.07) 64(86.49) 1.100 0.294 肝性脑病[例(%)] 51 6(13.95) 45(60.81) 24.284 <0.001 2.2 logistic回归和Pearson分析
综合考虑基线数据单变量分析结果及临床意义,筛选出年龄、WBC、TBil、Cr、INR、Alb、PLT、乳酸等12个指标进行单因素logistic回归分析,结果显示年龄、WBC、Na、Cr、TBil、INR、乳酸、PaO2/FiO2有统计学意义(P值均<0.05)。对单因素分析结果进行多重线性分析,显示各因素方差膨胀因子均<10,表明各因素之间不存在多重共线性。将上述因素进行多因素logistic回归分析,结果显示年龄、乳酸、INR是影响HBV-ACLF患者90 d预后的独立危险因素(P值均<0.05)(表 4)。Pearson相关分析显示,乳酸与WBC、肝性脑病存在相关性(r值分别为0.296、0.232,P值均<0.05)。
表 4 HBV-ACLF患者预后影响因素的多因素logistic分析Table 4. Multi-factor logistic analysis of the prognostic factors of HBV-ACLF指标 B值 SE Wald P值 OR 95%CI 年龄 0.073 0.024 9.174 0.002 1.075 1.026~1.127 INR 0.787 0.331 5.667 0.017 2.198 1.149~4.203 乳酸 0.359 0.182 3.888 0.049 1.431 1.002~2.044 2.3 各评分模型的分析
用ROC曲线评估乳酸、ALBI评分、MELD评分、MELD-Na评分、MESO评分、iMELD评分、CLIF-C ACLF评分预测HBV-ACLF患者90 d病死率的准确性(表 5),发现入院时乳酸可预测HBV-ACLF患者90 d的病死率(AUC=0.677,95%CI:0.579~0.775),截断值为3.15、灵敏度为0.405、特异度为0.930。MELD评分、MELD-Na评分、MESO评分、iMELD评分、CLIF-C ACLF评分对HBV-ACLF患者90 d的病死率均有预测价值(P值均<0.001),其预测价值CLIF-C ACLF>iMELD>MESO>MELD(MELD-Na)>ALBI。
表 5 各模型预测90 d病死率的的准确性Table 5. Accuracy of each model in predicting 90-d mortality rate评分模型 AUC 95%CI P值 cut-off值 灵敏度 特异度 ALBI 0.567 0.458~0.675 0.231 -1.233 9 0.595 0.558 乳酸 0.677 0.579~0.775 0.001 3.150 0 0.405 0.930 MELD 0.698 0.604~0.791 <0.001 29.574 6 0.432 0.953 MELD-Na 0.698 0.603~0.793 <0.001 31.935 7 0.527 0.837 MESO 0.709 0.617~0.802 <0.001 2.286 9 0.446 0.977 iMELD 0.766 0.682~0.851 <0.001 50.144 4 0.527 0.907 CLIF-C ACLF 0.832 0.761~0.904 <0.001 51.472 6 0.689 0.860 2.4 通过增加乳酸提高预后模型的预测价值
在六种评分的基础上相加乳酸,计算出新的评分(ALBI+乳酸、MELD+ 乳酸、MELD-Na+乳酸、MESO+乳酸、iMELD+乳酸、CLIF-C ACLF+乳酸)。ROC曲线分析显示,新的评分对HBV-ACLF患者的90 d病死率均有预测价值(P值均≤0.001)(表 6)。新旧模型成组绘制ROC曲线(图 1),显示新评分曲线下面积均有不同程度增加。进一步对新旧模型两两比较,发现AIBI与ALBI+乳酸差异有统计学意义(Z=2.209, P<0.05),MELD与MELD+乳酸、MELD-Na与MELD-Na+乳酸、MESO和MESO+乳酸、CLIF-C ACLF与CLIF-C ACLF+乳酸评分间差异均无统计学意义(Z分别为0.829、1.902、0.216、0.671,P值均>0.05)。
表 6 相加乳酸后六种新模型的预测价值Table 6. Predictive values of the six new models after summing lactate评分模型 AUC 95%CI P值 灵敏度 特异度 ALBI+乳酸 0.690 0.593~0.787 0.001 0.541 0.767 MELD+乳酸 0.709 0.617~0.801 <0.001 0.446 0.977 MELD-Na+乳酸 0.717 0.625~0.809 <0.001 0.622 0.767 MESO+乳酸 0.719 0.625~0.813 <0.001 0.446 0.907 iMELD+乳酸 0.775 0.692~0.858 <0.001 0.514 0.907 CLIF-C ACLF+乳酸 0.839 0.769~0.909 <0.001 0.622 0.953 3. 讨论
本研究通过对117例HBV-ACLF患者分析,发现INR、年龄、乳酸是影响HBV-ACLF患者90 d预后的独立危险因素。年龄越大的肝衰竭患者、死亡风险越高,这与以往研究[15-17]相一致。INR是反应凝血功能的常用指标、TBil是反应肝脏损伤的重要指标,既往研究[18]已经表明二者与肝衰竭预后密切相关,且被普遍接受及纳入ACLF诊断标准,但本研究仅表明INR为HBV-ACLF患者90 d预后的独立危险因素,TBil没有进入多因素分析,其原因一方面可能是大部分患者于本院就诊时TBil已经处于较高水平,导致了信息偏倚;另一方面可能是失访的14例和乳酸资料不全的51例患者排除于本研究之外,导致了选择偏倚。传统上,乳酸一直被认为是组织缺氧的标志,因为缺氧条件引起线粒体氧化受损,从而导致乳酸的过度产生和利用不足[19]。但高乳酸血症的确切生理机制一直备受争议,高乳酸血症与损伤或疾病严重程度的联系可以追溯到100年前O2债务理论假设[20]。但最新观点认为其机制为乳酸穿梭,这是一种在快速糖酵解细胞中产生乳酸为受体细胞提供能量底物的方式,而乳酸是一种燃料能量来源、糖化前体和信号分子。哺乳动物中的乳酸穿梭可以理解为一种菌株反应,其目的是减轻疾病和损伤的后果。乳酸血症不是损伤或疾病的原因,而是减轻损伤和疾病影响的机制[21]。
近年来,乳酸水平的波动引起了临床医生和研究人员的广泛关注,Cardoso等[22]发现基线乳酸水平与重症监护室病死率显著相关,其每增加1 mmol/L,病死率增加8%。Kruse等[23]分析了重症肝病患者高乳酸血症的发生率,并表明乳酸酸中毒与休克的临床证据和医院病死率的增加有关。Jeppesen等[24]发现,肝硬化患者的乳酸水平比健康人高,而且乳酸水平随着肝硬化的严重程度增加而增加。Drolz等[25]研究表明乳酸是一个预测器官衰竭和肝硬化危重患者短期病死率良好的独立指标,但很少有研究关注乳酸在HBV-ACLF预后中的价值。HBV-ACLF是一种以严重炎症、免疫功能障碍和肝损伤为特征终末期肝病,病死率高达60%~75%[26-27]。在临床实践中,预测这种疾病的进展是临床医生面临的巨大挑战。先前的研究已经揭示了ALBI评分、MELD评分、MELD-Na评分、MESO评分、iMELD评分、CLIF-C ACLF评分在ACLF患者预后预测的有效性[28-29],但乳酸对现有评分系统的潜在贡献尚未得到验证。本研究表明,乳酸预测HBV-ACLF患者90 d预后AUC为0.677,灵敏度、特异度分别为0.405、0.930。当乳酸≥3.15时,HBV-ACLF患者病死率高达90.91%。将乳酸与六种模型简单相加发现,模型AUC均有不同程度扩大,表明乳酸与现有模型联合很有可能提高其预测效能。
本研究还表明乳酸是HBV-ACLF预后的独立危险因素,其与HBV-ACLF患者机体感染、肝性脑病存在相关性。有证据[30-31]表明T淋巴细胞通过控制适应性免疫反应,在病毒或细菌感染方面发挥重要作用。病原体引起的T淋巴细胞激活会导致线粒体代谢和耗氧量的迅速增加,但最显著的代谢变化是糖酵解的急剧增加,导致乳酸的产生显著增加[32]。如果新陈代谢不能满足细胞的需求,细胞功能就会受损或发生细胞凋亡。反之,代谢过剩可能会阻止细胞凋亡,促进或增强T淋巴细胞的活化和功能,并可能导致炎症性疾病[33-34],HBV-ACLF患者腹膜感染或肺部感染等炎症反应可能通过这一机制促进体内乳酸的堆积。从生物学角度来说,乳酸是多种病因引起的生理应激、微循环障碍或组织缺氧的替代物[35-36],主要通过糖异生、肝脏的三羧酸循环和肾脏分泌三条途径以恒定的速率被清除,一旦体内生成或排出异常,就会导致乳酸在体内蓄积[37]。此外,急性肝衰竭诱导肝性脑病期间,存在着脑细胞外区乳酸水平升高,可能是乳酸在星形胶质细胞中的产生和释放增加,或者是神经元摄取和新陈代谢的减少所致。同时,肝性脑病时发生的血氨水平升高能够降低α-酮戊二酸脱氢酶活性,影响能量代谢而造成脑乳酸增加。这些蓄积的脑乳酸很可能引起脑水肿的发生,促进了HBV-ACLF死亡事件的发生[38]。
本研究发现乳酸是HBV-ACLF患者90 d预后的独立危险因素,入院时进行乳酸检测有助于预后评估和临床决策。将乳酸纳入现有模型,可能提高其预测价值。此外,本研究存在一定的局限性:首先,这是一项单中心回顾性研究,一部分患者的失访和资料不全,导致了选择偏倚;第二,缺乏乳酸动态变化和乳酸清除率的的预测作用,因为没有常规测量动脉血乳酸;第三,由于缺少免疫相关的信息,未能评估乳酸与其之间的相关性。
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表 1 CLIF-C OF评分
Table 1. CLIF-C OF scores
器官/系统 1分 2分 3分 肝脏(TBil, mg/dL) <6 6~12 >12 肾脏(Cr, mg/dL) <2 2~3.4 ≥3.5或肾脏替代治疗 凝血功能(INR) <2 2~2.4 ≥2.5 神经(感性脑病分级) 0 Ⅰ~Ⅱ Ⅲ~Ⅳ 循环(平均动脉压,mmHg) ≥70 <70 应用血管活性药物
(去甲肾上腺素、多巴胺、肾上腺素)呼吸 PaO2/FiO2 >300 201~300 ≤200 SPO2/FiO2 >357 215~357 ≤214 注:Cr,肌酐;PaO2/FiO2,氧分压/氧浓度;SpO2/FiO2,血氧饱和度/氧浓度。 表 2 入组时基线资料的比较分析
Table 2. Comparative analysis of baseline information at enrollment
指标 生存组(n=43) 死亡组(n=74) 统计值 P值 年龄(岁) 44.05±10.32 49.70±12.33 t=2.536 0.013 男/女(例) 31/12 55/19 χ2=0.070 0.792 WBC(×109/L) 6.25(5.10~8.20) 7.83(5.90~11.57) Z=-2.813 0.005 红细胞分布宽度(%) 16.20(14.60~17.80) 17.45(15.28~18.60) Z=-1.804 0.071 Na(mmol/L) 135.00(132.42~136.87) 132.96(128.42~136.0) Z=-2.044 0.041 血小板压积(%) 0.56(0.31~0.90) 0.59(0.40~1.02) Z=-0.933 0.351 PLT(×109/L) 122(90~142) 91(60~133.5) Z=-1.883 0.060 Alb(g/L) 29.29(24.81~32.57) 28.22(25.54~31.42) Z=-0.334 0.739 INR 2.52(1.96~3.03) 2.85(2.43~3.59) Z=-2.855 0.004 Cr(mg/dL) 0.72(0.62~0.88) 0.84(0.62~1.16) Z=-1.916 0.055 TBil(mg/dL) 17.08(13.46~20.58) 19.67(14.12~26.51) Z=-1.713 0.087 AST(U/L) 222.72(111.14~563.52) 215.95(105.59~529.12) Z=-0.636 0.525 ALT(U/L) 362.10(161.57~682.10) 197.87(64.42~648.65) Z=-1.269 0.204 乳酸(mmol/L) 2.30(1.80~2.70) 2.60(2.00~3.82) Z=-3.186 0.001 ALBI评分 -1.30(-1.59~-0.94) -1.16(-1.48~-0.92) Z=-1.198 0.231 MELD评分 24.29±4.27 28.99±6.74 t=4.615 <0.001 MELD-Na评分 25.66±8.33 34.28±13.63 t=4.247 <0.001 MESO评分 1.81±0.34 2.21±0.53 t=4.941 <0.001 iMELD评分 43.61±5.69 51.73±9.37 t=5.832 <0.001 CLIF-C ACLF评分 45.48±6.71 56.70±9.22 t=7.562 <0.001 糖尿病[例(%)] 3(6.98) 14(18.92) χ2=3.123 0.077 肝硬化[例(%)] 25(58.14) 52(70.27) χ2=1.779 0.182 人工肝支持[例(%)] 26(60.47) 42(56.76) χ2=0.154 0.695 表 3 两组并发症发生情况比较
Table 3. Comparison of the occurrence of complications between the two groups
指标 例数 生存组(n=43) 死亡组(n=74) χ2值 P值 上消化道出血[例(%)] 15 1(2.33) 14(18.92) 6.700 0.010 肺部感染或感染性休克[例(%)] 41 8(18.60) 33(44.59) 8.070 0.004 肝肾综合征[例(%)] 13 0 13(17.57) 6.813 0.009 腹水[例(%)] 98 34(79.07) 64(86.49) 1.100 0.294 肝性脑病[例(%)] 51 6(13.95) 45(60.81) 24.284 <0.001 表 4 HBV-ACLF患者预后影响因素的多因素logistic分析
Table 4. Multi-factor logistic analysis of the prognostic factors of HBV-ACLF
指标 B值 SE Wald P值 OR 95%CI 年龄 0.073 0.024 9.174 0.002 1.075 1.026~1.127 INR 0.787 0.331 5.667 0.017 2.198 1.149~4.203 乳酸 0.359 0.182 3.888 0.049 1.431 1.002~2.044 表 5 各模型预测90 d病死率的的准确性
Table 5. Accuracy of each model in predicting 90-d mortality rate
评分模型 AUC 95%CI P值 cut-off值 灵敏度 特异度 ALBI 0.567 0.458~0.675 0.231 -1.233 9 0.595 0.558 乳酸 0.677 0.579~0.775 0.001 3.150 0 0.405 0.930 MELD 0.698 0.604~0.791 <0.001 29.574 6 0.432 0.953 MELD-Na 0.698 0.603~0.793 <0.001 31.935 7 0.527 0.837 MESO 0.709 0.617~0.802 <0.001 2.286 9 0.446 0.977 iMELD 0.766 0.682~0.851 <0.001 50.144 4 0.527 0.907 CLIF-C ACLF 0.832 0.761~0.904 <0.001 51.472 6 0.689 0.860 表 6 相加乳酸后六种新模型的预测价值
Table 6. Predictive values of the six new models after summing lactate
评分模型 AUC 95%CI P值 灵敏度 特异度 ALBI+乳酸 0.690 0.593~0.787 0.001 0.541 0.767 MELD+乳酸 0.709 0.617~0.801 <0.001 0.446 0.977 MELD-Na+乳酸 0.717 0.625~0.809 <0.001 0.622 0.767 MESO+乳酸 0.719 0.625~0.813 <0.001 0.446 0.907 iMELD+乳酸 0.775 0.692~0.858 <0.001 0.514 0.907 CLIF-C ACLF+乳酸 0.839 0.769~0.909 <0.001 0.622 0.953 -
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