自体骨髓间充质干细胞移植治疗难治性肝硬化腹水患者的临床疗效观察

Clinical observation of hepatic cirrhosis patients with refractory ascites undergoing autologous bone marrow masenchymal stem cells transplantation

目的观察自体骨髓间充质干细胞(BMSC)移植治疗肝硬化难治性腹水的疗效及安全性。方法对2010年9月至2013年9月入住南京总医院消化内科经正规利尿、补充白蛋白达3个月以上且疗效欠佳的32例肝硬化腹水患者,在原有治疗基础上加用自体BMSC移植治疗,分别于治疗前、治疗后1个月及3个月观察腹围、体重、24 h尿量、血清尿素氮、肌酐、尿钠及血清蛋白浓度等指标变化。采用方差分析、配对t检验和Wilcoxon检验进行统计学分析。结果治疗前,患者体重、腹围、24 h尿量及血清尿素氮、肌酐、血清总蛋白、血清白蛋白及尿钠排出水平分别为(66.9±3.8)kg、(94.0±3.6)cm、(966±138.7)ml、(10.5±3.6)mmol/L、(112.4±30.6)μmol/L、(63.8±4.2)g/L、(32.1±2.7)g/L、(43.8±2.3)mmol/L;治疗后1个月,分别为(66.0±3.9)kg、(93.0±3.6)cm、(1032±154.8)ml、(9.9±3.2)mmol/L、(104.8±25.6)μmol/L、(65.3±3.5)g/L、(32.6±2.9)g/L、(44.7±2.7)mmol/L;治疗后3个月,分别为(56.2±3.7)kg、(80.5±4.5)cm、(1530±180.6)ml、(7.9±2.3)mmol/L、(88.7±22.2)μmol/L、(72.8±3.3)g/L、(39.2±1.5)g/L。3个组别8个指标均数比较有统计学意义(F=78.194、117.689、120.527、6.558、6.712、54.827、83.421、493.776,均P=0.000)。治疗后1个月与治疗前水平差异无统计学意义(t分别为0.587、0.636、0.559、0.556、0.678、0.522、0.611、0.592;P=0.331、0.266、0.101、0.416、0.25、0.107、0.447);而治疗后3个月,患者的体重、腹围较治疗前及治疗后1个月均明显减少,24 h尿量明显增加(与治疗前比较,t=3.722、3.784、3.821,与治疗后1个月比较,t=3.921、3.834、3.944,均P=0.000),血清尿素氮、肌酐水平较治疗前及治疗后1个月均明显下降;而血清总蛋白、白蛋白及尿钠排出水平均明显升高(与治疗前比较,t=2.182、2.338、2.182、2.412、2.136,P尿素、肌酐=0.001,其余P=0.000;与治疗后1个月比较,t=2.392、2.283、2.194、2.331、2.442,均P=0.000),治疗后1个月总有效率为18.75﹪,3个月后治疗总有效率达100﹪,疗效差异有统计学意义(Z=-5.014,P=0.000),无严重并发症发生。结论自体BMSC移植术治疗肝硬化难治性腹水安全有效,且方法简便易行。

Objective To observe the effectiveness and security of hepatic cirrhosis patients with refractory ascites undergoing autologous bone marrow masenchymal stem cells transplantation. Methods A retrospective study was conducted on 32 hepatic cirrhosis patients with refractory ascites. These patients had accepted diuretic therapy and supplement of human albumin over three months, but the therapeutic effect is poor. On the base of original treatment, all the patients accepted autologous bone marrow masenchymal stem cells transplantation. We observed respectively the difference of clinical symptoms, weight, and abdominal perimeter, 24 h volume of urine, serum urea nitrogen, serum creatinine, serum total protein,serum albumin and urine sodium at pre-procedure, 1 month and 3 months post-treatment. Analysis of two-way ANOVA, t test and Wilcoxon test were used in the study. Results At baseline, body weight, abdominal perimeter, 24 h volume of urine, serum urea nitrogen, serum creatinine, serum total protein, serum albumin and urin sodium were （66.9 ± 3.8） kg, （94.0 ± 3.6） cm, （966.0 ± 138.7） ml, （10.5± 3.6） mmol/L, （112.4 ±30.6） μmol/L, （63.8 ±4.2） g/L, （32.1 ± 2.7） g/L, and （43.8 ± 2.3） mmol/L, respectively. At 1 month post-transplantation, they were （66.0 ± 3.9） kg, （93.0 ± 3.6） cm, （ 1032 ± 154.8） ml, （9.9 ±3.2） mmol/L, （ 104.8 ± 25.6） μmol/ L, （65.3± 3.5） g/L, （32.6 ± 2.9） g/L, and （44.7 ± 2.7） mmol/L, respectively. At 3 month post-transplantation, they were （56.2 ± 3.7） kg, （80.5 ± 4.5）cm, （1530 ±180.6） ml, （7.9 ±2.3） mmol/L, （88.7 ± 22.2） μmol/L, （72.8 ± 3.3） g/L, and （39.2± 1.5） g/L, respectively. There was significant difference among for all parameters at the three time points （F = 78.194, 117.689, 120.527, 6.558, 6.712, 54.827, 83.421, and 493.776 respectively, P = 0.000 for all）. The improvement was no significant between baseline and at 1 month post-transplantation. There was slight improvement in the patients＇ clinical symptoms, （t = 0.587, 0.636, 0.559, 0.556, 0.678, 0.522, 0.611, and 0.592 respectively; P = 0.331, 0.266, 0.101, 0.416, 0.25, 0.107, and 0.4475 respectively）. However, there was significant improvement at 3 months compared to both the base and 1 month post-transplantation （compared to baseline, t = 3.722, 3.784, 3.821, 2.182, 2.338, 2.182, 2.412, and 2.136 respectively, P 〈 0.001 for all; compared to 1 month post- transplantation, t = 3.921, 3.834, 3.944, 2.392, 2.283, 2.194, 2.331, and 2.442 respectively, P = 0.000 for all）. The rate of improvement was only 18.75 % at 1 month, but increased to 100 % at 3 months （Z = -5.014, P = 0.000）. There was no severe complication. Conclusion Autologous bone marrow masenchymal stem cells transplantation is safe and effective for hepatic cirrhosis patients with refractory ascites.