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人工肝治疗肝衰竭患者血红蛋白水平的变化及其影响因素
DOI: 10.12449/JCH250116
伦理学声明：本研究方案于2021年12月16日经由福建医科大学孟超肝胆医院伦理委员会审批，批号：科审2021_145_01。
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：林英负责数据采集与整理，论文初稿撰写；陈力、彭菲负责数据采集与整理；林建辉负责研究方案设计、论文修改；卓传尚负责研究方案设计与终审论文。
Changes in hemoglobin and related influencing factors in patients with liver failure undergoing artificial liver support therapy
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摘要:
目的 探讨肝衰竭患者接受人工肝治疗后血红蛋白（Hb）变化趋势和影响因素。 方法 选取2018年1月—12月在福建医科大学孟超肝胆医院接受人工肝治疗的肝衰竭患者106例，分析患者的临床资料与Hb、平均红细胞体积（MCV）、平均红细胞血红蛋白含量（MCH）、平均红细胞血红蛋白浓度（MCHC）和红细胞分布宽度变异系数（RDW-CV）等红细胞参数。重复测量资料组间比较采用单因素重复测量方差分析，两两比较采用配对t检验；偏态分布的计量资料多组间比较采用Kruskal-Wallis H检验，两两比较采用Mann-Whitney U检验。采用单因素及多因素线性回归分析人工肝治疗后Hb降低的影响因素。 结果 106例肝衰竭患者接受606人次人工肝治疗，其中402人次治疗前后均有Hb检测结果，肝衰竭患者接受人工肝治疗术后Hb［（97.49±20.51）g/L］较术前［（109.38±20.22）g/L］下降（t=32.764，P<0.001）。进一步对14例肝衰竭患者纵向观察，末次人工肝治疗术前Hb为（108.50±21.61）g/L，术后次日Hb［（103.14±19.15）g/L］较前恢复，术后第3天Hb［（102.57±21.73）g/L］未进一步回升，术后第7天Hb再次升高［（105.57±22.04）g/L］。肝衰竭患者术后次日Hb水平随着治疗次数的增加而降低（F=8.996，P<0.001），而MCV和MCH随着治疗次数的增加逐渐增高（F值分别为9.154和13.460，P值分别为0.004和<0.001），RDW-CV则先逐渐升高后下降（F=4.520，P=0.032），MCHC呈上下波动，无明显趋势（F=0.811，P=0.494）。多因素线性回归分析显示，人工肝操作时长、模式和首次治疗是人工肝治疗后Hb减少的独立危险因素（P值均<0.05）。 结论 人工肝治疗可影响肝衰竭患者外周Hb水平，应加强肝衰竭人工肝治疗期间的患者血液管理。 Abstract:Objective To investigate the changing trend of hemoglobin （Hb） and related influencing factors in patients with liver failure after artificial liver support system （ALSS） therapy. Methods A total of 106 patients with liver failure who were hospitalized and received ALSS therapy in our hospital from January to December 2018 were enrolled and analyzed in terms of clinical data and red blood cell parameters such as Hb， mean corpuscular volume （MCV）， mean corpuscular hemoglobin （MCH）， mean corpuscular hemoglobin concentration （MCHC）， and red blood cell distribution width-coefficient of variation （RDW-CV）. A one-way repeated-measures analysis of variance was used for comparison of continuous data with repeated measurement between groups， and the paired t-test was used for comparison between two groups. The Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups， the Mann-Whitney U test was used for further comparison between two groups. Univariate and multivariate linear regression analyses were used to identify the influencing factors for the reduction in Hb after ALSS therapy. Results The 106 patients with liver failure received 606 sessions of ALSS therapy， and Hb was measured for 402 sessions before and after treatment. There was a significant reduction in Hb after ALSS therapy in the patients with liver failure （97.49±20.51 g/L vs 109.38±20.22 g/L， t=32.764， P<0.001）. Longitudinal observation was further performed for 14 patients with liver failure， and the results showed that the level of Hb was 108.50±21.61 g/L before the last session of ALSS therapy， with certain recovery compared with the level of Hb （103.14±19.15 g/L） on the second day after ALSS， and there was an increase in Hb on day 3 （102.57±21.73 g/L） and day 7 （105.57±22.04 g/L） after surgery. The level of Hb in patients with liver failure on the second day after ALSS decreased with the increase in the number of ALSS sessions （F=8.996， P<0.001）， while MCV and MCH gradually increased with the increase in the number of ALSS sessions （F=9.154 and 13.460， P=0.004 and P<0.001）， and RDW-CV first gradually increased and then gradually decreased （F=4.520， P=0.032）； MCHC showed fluctuations with no clear trend （F=0.811， P=0.494）. The multivariate linear regression analysis showed that the duration of ALSS therapy， the mode of ALSS therapy， and initial treatment were independent risk factors for the reduction in Hb after ALSS therapy. Conclusion ALSS therapy can influence the level of peripheral blood Hb in patients with liver failure， and patient blood management should be strengthened for patients with liver failure who are receiving ALSS therapy. -
Key words:
- Liver Failure /
- Liver， Artificial /
- Hemoglobins
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图 3 人工肝治疗次数对Hb及红细胞参数的影响
Figure 3. The mean values of hemoglobin and red blood cell parameters in patients on the first day after each ALSS therapy
表 1 肝衰竭患者人工肝治疗前的基本临床和实验室资料
Table 1. Clinical and laboratory data before artificial liver therapy in patients with liver failure
指标 数值 年龄（岁） 46（37～55） 性别［例（%）］ 男 89（83.96） 女 17（16.04） 肝衰竭类型［例（%）］ 亚急性肝衰竭 6（5.66） 慢加急性（亚急性）肝衰竭 93（87.74） 慢性肝衰竭 7（6.60） 肝衰竭分期［例（%）］ 早期 9（8.49） 中期 63（59.43） 晚期 34（32.08） 肝衰竭病因［例（%）］ 肝炎病毒 95（89.62） 药物性 3（2.83） 酒精性 1（0.94） 原因不明 7（6.60） 人工肝治疗次数［例（%）］ ≤2次 15（14.15） 3次 17（16.04） 4次 10（9.43） 5次 14（13.21） 6次 12（11.32） 7次 14（13.21） ≥8次 24（22.64） 腹水（无/有） 55/51 肝性脑病分期（0/1/2/3/4） 85/11/6/2/2 身高（cm） 167.27±7.25 体质量（kg） 65（59～74） BMI（kg/m2） 23.54±3.33 血容量（mL） 4 408±552 MELD评分（分） 25.27±5.86 TBil（μmol） 373.2（333.5～464.0） Alb（g/L） 32.04±4.87 ALT（U/L） 323（113～665） AST（U/L） 225（111～498） Cr（μmol/L） 66（60～80） Amon（μmol/L） 58（44～83） PT（s） 24.4（20.7～31.3） INR 2.20（1.70～2.98） Hb（g/L） 123.64±21.34 
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表 2 8例肝衰竭患者10次人工肝术后次日红细胞参数值
Table 2. Red blood cell parameters on the day after 10 artificial liver therapy in 8 patients with liver failure
次数 Hb（g/L） RDW-CV（%） MCV（fL） MCH（pg） MCHC（g/L） 首次术前 124.13±17.27 15.49±2.48 93.26±6.76 31.69±1.72 340.38±17.25 1次 115.75±18.03 15.76±2.61 95.25±8.77 32.05±2.27 337.25±11.32 2次 112.00±16.20 17.19±1.67 97.05±9.59 32.76±2.58 338.63±17.11 3次 114.75±20.89 18.61±1.81 97.99±10.80 32.86±2.77 336.25±15.71 4次 106.38±18.29 19.80±3.24 98.55±10.93 33.49±3.24 339.38±13.53 5次 109.13±17.02 20.91±4.92 99.14±9.78 33.90±3.28 342.13±10.56 6次 102.50±17.37 21.34±5.68 100.51±9.94 34.09±3.06 339.50±13.24 7次 99.88±11.00 21.36±6.23 101.33±9.45 34.24±2.70 338.63±12.32 8次 98.63±10.36 21.23±6.25 101.59±8.20 35.03±2.81 345.13±13.52 9次 97.13±11.83 20.88±6.17 102.70±6.40 35.23±2.42 343.13±8.46 10次 92.00±10.94 18.99±4.87 104.90±5.15 35.76±2.11 341.00±10.03 F值 8.996 4.520 9.154 13.460 0.811 P值 <0.001 0.032 0.004 <0.001 0.494
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表 3 人工肝治疗后Hb降低的影响因素分析
Table 3. Analysis of risk factors affecting Hb reduction after artificial liver therapy
参数 单因素线性回归分析 多因素线性回归分析 B值 SE β值 t值 P值 β值 t值 P值 年龄 0.045 0.028 0.081 1.634 0.103 性别 -0.025 0.400 -0.003 -0.062 0.950 身高 -0.014 0.053 -0.014 -0.269 0.788 体质量 -0.078 0.035 -0.114 -2.246 0.025 -0.101 -1.015 0.311 BMI -0.276 0.111 -0.125 -2.477 0.014 -0.015 -0.148 0.883 血容量 -0.001 0.001 -0.065 -1.305 0.193 肝衰竭类型 -0.124 0.967 -0.006 -0.128 0.898 肝衰竭分期 0.787 0.653 0.060 1.205 0.229 肝衰竭病因 0.881 0.493 0.089 1.788 0.075 0.057 -1.143 0.254 MELD评分 0.047 0.064 0.036 0.723 0.470 腹水 -0.033 0.325 -0.005 -0.102 0.919 肝性脑病 -0.198 0.338 -0.029 -0.584 0.560 人工肝治疗时长 0.009 0.004 0.105 2.119 0.035 0.189 3.374 0.001 人工肝模式 -0.604 0.289 -0.104 -2.087 0.038 -0.158 -2.841 0.005 人工肝次数 -0.387 0.119 -0.161 -3.256 0.001 -0.047 -0.825 0.410 首次人工肝 3.653 0.930 0.193 3.928 <0.001 0.157 2.768 0.006
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