Transfusion with human umbilical cord mesenchymal stem cells improves liver function in hepatitis B patients with decompensated liver cirrhosis

doi:10.3969/j.issn.2095-4344.0922

Abstract

Abstract:

BACKGROUND: Decompensated liver cirrhosis, a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation.
OBJECTIVE: To evaluate the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) transplantation in hepatitis B patients as a treatment for decompensated liver cirrhosis.
METHODS: The mesenchymal stem cell (MSC) treatment group contained 17 hepatitis B patients with decompensated liver cirrhosis and the control group contained 17 matched controls. All patients received conventional treatment for hepatitis B cirrhosis, including the oral administration of antiviral nucleoside analogues. Patients in the MSC treatment group received hUC-MSC infusions into the elbow vein, while control patients received no injection. Follow-up examinations were conducted after treatment to evaluate clinical symptoms, liver function and blood coagulation function. In addition, the severity of cirrhosis was assessed based on the Child-Pugh and Model for End-Stage Liver Disease scores.
RESULTS AND CONCLUSION: In this study, we revealed that hUC-MSC-treated patients had an improvement in liver function, as indicated by the recovered albumin, bilirubin, lactate dehydrogenase and alkaline phosphatase levels to some extent. Additionally, hUC-MSC-treated patients had better Child-Pugh and Model for End Stage Liver Disease scores than control patients. Therefore, our findings reveal that the transfusion with hUC-MSCs improves the liver function, which represents a safe approach for treating decompensated liver cirrhosis in hepatitis B patients.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Liver Cirrhosis, Umbilical Cord, Tissue Engineering

CLC Number:

R394.2

Fu Qing-chun, Jin Yin-peng, Wang Xiao-jin, Li Li, Wang Xi, Li Hong-chao, Wang Zhao-jing, Zhou Feng, Zang Zu-sheng, Shi Li-qin, Li Zhen-yu, Chen Cheng-wei. Transfusion with human umbilical cord mesenchymal stem cells improves liver function in hepatitis B patients with decompensated liver cirrhosis[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(25): 3993-4000.

Figures/Tables 2

Quantitative analysis of patients The study flow is presented in Figure 1. A total of 138 hepatitis B patients with DLC were recruited. Three patients were excluded because they did not meet the inclusion criteria, and 101 patients were excluded because they did not provide one-on-one correspondence. Seventeen hepatitis B patients were recruited to the human umbilical cord-derived mesenchymal stem cell (hUC-MSC) treatment group and the control group contained 17 clinically matched individuals. Baseline comparisons and clinical symptoms The baseline characteristics are presented in Table 1. The patients in the MSC-treated and control groups were similar regarding sex, age and biochemical data. The baseline Child-Pugh (P=0.149) and MELD (P=0.661) scores were also similar. The patients in the two groups did not differ regarding the course of DLC (P=0.333; Figure 2A). and control groups had undetectable levels of HBV DNA in their serum, with no significant differences detected between the groups (P=0.247). The antiviral length was also comparable between the groups (P=0.704). Ascites gradually decreased in both the MSC-treatment and control groups following the administration of albumin and diuretics and no significant differences were detected between the groups (P=0.203). Liver function tests Forty-eight weeks after treatment, Alb levels increased from (28.9±2.8) g/L to (33.9±5.7) g/L in the MSC-treatment group, which was significantly higher than the baseline (P < 0.05; Figure 2A). PAB increased from (62.1±32.7) g/L to (98.7±41.6) g/L in MSC-treated patients, which was also significantly higher than the baseline value (P < 0.05; Figure 2B). Alb and PAB levels did not differ significantly to the baseline values after 48 weeks of conventional treatment alone (Figure 2A, B). The differences in Alb and PAB levels were not significant between the two groups at different time points (Figure 2A, B). TB levels at 48 weeks after treatment were: MSC-treatment group, 53.9 to 37.0 μmol/L; control group, (54.6±45.3) to (55.7±47.0) μmol/L (Figure 2C, D). The differences between the two groups at each time point were not statistically significant. The levels of LDH and AKP were significantly lower in the MSC-treatment group compared to the control group 48 weeks after treatment (P < 0.05; Figure 2E, F). Forty-eight weeks after treatment, the LDH values were: MSC-treatment group, (191.4±63.7) U/L; control group, (272.2±105.3) U/L. The AKP values 48 weeks after treatment were: MSC-treatment group, (87.2±33.7) U/L; control group, (133.8±58.3) U/L. The levels of ALT, γ-GT and CPK did not differ significantly between the MSC-treatment and control groups at all time points (Figure 2G, H, I). Blood coagulation tests Cirrhosis patients have an increased risk for bleeding. We assessed the coagulation function in HBV patients with DLC by measuring the PT and APTT. The PT did not differ significantly between the MSC-treated and control patients at various time points after treatment (Figure 3A). We observed a faster APTT in the MSC-treatment group 4 weeks after treatment and the APTT continued to decrease in the MSC-treated patients until 48 weeks after treatment (Figure 3B). The APPT values at 48 weeks after treatment were: MSC-treatment group, 39.9 seconds (7.5-second decrease); control group, 43.1 seconds (7.5-second increase). The differences between the two groups at each time point were not statistically significant. Renal function Cr levels in the blood were measured to assess renal function[35]. We detected a decline in Cr levels in the blood of MSC-treated patients compared to control patients (Figure 3C), which indicated improved renal function. However these differences were not statistically significant, although this may reflect the low number of participants, rather than a genuine lack of significance. Child-Pugh and MELD scores The Child-Pugh and MELD scores were calculated to evaluate the severity of cirrhosis in the patients[30]. The Child-Pugh score declined significantly from 9.4 points at the baseline to 7.5 points measured 48 weeks after treatment in the MSC-treatment group, (P < 0.05; Figure 3D), indicating a better prognosis. The MELD score also declined from 15.8 to 13.3 points in MSC-treated patients, while in the control group, the MELD score rose slightly from 15.1 points at the baseline to 15.5 points 48 weeks after treatment (Figure 3E). This indicates a better prognosis in patients treated with hUC-MSCs compared to patients who received conventional treatment alone, although the differences between the two groups in each time point were not statistically significant. Evaluation of potential complications following hUC-MSC transfusion No abnormal changes were detected in the vital signs, electrocardiogram results and renal function of patients following transfusion with hUC-MSCs which were observed at the time of transfusion. Two patients developed a fever and a reduced platelet count was detected in two further patients. In one patient we observed an increase in the INR to 8.21, which recovered baseline after 72 hours without any treatment, although this decreased within 4 days and no hemorrhage-related complications were observed. No tumor development was observed during follow-up examinations in MSC-treated patients. Other potential serious adverse reactions associated with end-stage liver diseases, such as hepatorenal syndrome, hepatic encephalopathy and pleural effusion, were not related to MSC-treatment. There was no statistically significant difference in the adversity of the reaction between the two groups."

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