The clinical characteristics of non-UC-MSCs and UC-MSCs transplantation ELSD patients
For non-UC-MSCs transplantation ELSD patients (Table 1), there were totally fifty patients including 29 males and 21 females. The mean of age was 49.86 years (range, 38-64 years). The mean body weight of the patients was 63.44 kg. The mean body height of the patients was 163.98 cm. The liver cirrhosis caused by hepatitis B virus infection and caused by hepatitis C virus infection in patients were 38 cases (95%) and 3 cases (7.5%), respectively. The number of patients of alcoholic cirrhosis and autoimmune cirrhosis were 8 out of 50 (20%) and 1 out 50 (2.5%), respectively. The number of grade A, B and C of Child-Pugh score were 18 cases, 11 cases, and 3 cases, respectively.
Table 1
Clinical characteristic of patients with Cirrhosis without UC-MSCs transplantation.
Variable
|
Patients with Cirrhosis (n=50)
|
Sex male n (%)
|
29 (58%)
|
Sex female n (%)
|
21 (42%)
|
Age (years)
|
49.86
|
Body weight (kg)
|
63.44
|
Body height (cm)
|
163.98
|
Aetiology
|
|
Hepatitis B cirrhosis
|
38 (95%)
|
Hepatitis C cirrhosis
|
3 (7.5%)
|
Alcoholic cirrhosis
|
8 (20%)
|
Autoimmune cirrhosis
|
1 (2.5%)
|
Child-Pugh class
|
|
A (5-6)
|
18
|
B (7-9)
|
11
|
C (≥10)
|
3
|
Regarding UC-MSCs transplantation ELSD patients (Table 2), there were totally 45 patients including 35 males and 10 females. The mean of age was 48.18 years (range, 35-65 years). The mean body weight of the patients was 62.8 kg. The mean body height of the patients was 165.84 cm. The liver cirrhosis caused by hepatitis B virus infection in patients was 31 cases (68.9%), and caused by hepatitis C virus infection in patients was 7 cases (15.6%). The number of patients of alcoholic cirrhosis was 5 out of 45 (11.1%), and the number of patients of autoimmune cirrhosis was 2 out 50 (4.4%). The number of grade A of Child-Pugh score was 39 cases, the number of grade B of Child-Pugh score was 4 cases, and there were no patients to be defined as grade C.
Table 2
Clinical characteristic of patients with Cirrhosis following UC-MSCs transplantation.
Variable
|
Patients with Cirrhosis (n=50)
|
Sex male n (%)
|
35 (77.8%)
|
Sex female n (%)
|
10 (22.2%)
|
Age (years)
|
48.18
|
Body weight (kg)
|
62.8
|
Body height (cm)
|
165.84
|
Aetiology
|
|
Hepatitis B cirrhosis
|
31 (68.9%)
|
Hepatitis C cirrhosis
|
7 (15.6%)
|
Alcoholic cirrhosis
|
5 (11.1%)
|
Autoimmune cirrhosis
|
2 (4.4%)
|
Child-Pugh class
|
|
A (5-6)
|
39
|
B (7-9)
|
4
|
C (≥10)
|
0
|
UC-MSCs decreased incidence of the liver cancer
To investigate effects of UC-MSCs on the incidence of the liver cancer in ELSD patients, the number of liver cancer patients in non-UC-MSCs and UC-MSCs groups was calculated. It was found that the number of liver cancer patients in non-UC-MSCs group was 6 out 50 (12%), while the number of liver cancer patients in UC-MSCs group was 1 out 45 (2.2%) (Figure 2). Thus, it seems that UC-MSCs reduced the incidence of liver cancer.
Survival analysis
To examine survival situation of the ELSD patients with and without UC-MSCs transplantation, the survival curves were generated. Three (two were severe jaundice and hypohepatia, one was hypoproteinemia and hepatorenal syndrome) out of 50 non-UC-MSCs transplantation patients died, while two (one was hepatorenal syndrome and multiple organ failure, and one died from hepatorenal syndrome) out of 45 UC-MSCs patients died. The liver cancer epidemiology showed gender difference in the patients (17), thus, the survival curves stratified by gender towards non-UC-MSCs and UC-MSCs transplantation ELSD patients were established. Interestingly, it indicated that the survival percentage in male patients was higher than female patients in UC-MSCs transplantation group (Figure 3A); on the contrary, the survival percentage in female patients was higher than male patients in non-UC-MSCs group (Figure 3B). The survival percentage in ELSD patients treated with UC-MSCs transplantation was higher than in patients treated with non-UC-MSCs transplantation (Figure 3C). So, UC-MSCs transplantation might increase survival percentage in ESLD patients.
Inflammation and fibrosis scores using Ishak system and Child-Pugh class analysis for ELSD patients with and without UC-MSCs transplantation
To evaluate the inflammation and fibrosis during follow-up period for ELSD patients with and without UC-MSCs transplantation, the inflammation and fibrosis scores using Ishak system were calculated. It was shown that inflammation score decreased over the follow-up time, and inflammation score of UC-MSCs transplantation ELSD patients was lower than non-UC-MSCs transplantation patients in late follow-up period (12, 36, and 60 month) (Figure 4A). For fibrosis, it was found that the fibrosis score was decreased over the time in ELSD patients with UC-MSCs transplantation, while it was increased over the time in ELSD patients without UC-MSCs transplantation (Figure 4B). Interestingly, inflammation score in UC-MSCs transplantation patients was higher than in non-UC-MSCs transplantation ELSD patients at the beginning of transplantation, while the inflammation score in UC-MSCs transplantation ELSD patients was lower than in non-UC-MSCs transplantation ELSD patients at 60th month of follow-up. Taken together, it was plausible that UC-MSCs transplantation could relieve the liver inflammation and fibrosis compared with in ELSD patients without UC-MSCs transplantation patients.
The Child-Pugh score was one of the most indexes to assess severity of liver cirrhosis (5). To further investigate the effects of the UC-MSCs transplantation on cirrhosis in ELSD patients, a Child-Pugh class analysis was executed. It was shown that the number of patients with Child-Pugh class A was increased while the number of patients with Child-Pugh class B was decreased over the follow-up time, and the number of patients with Child-Pugh class C was declined first then climbed up in non-UC-MSCs transplanted ELSD patients (Figure 5A). For UC-MSCs transplanted ELSD patients, it was indicated that the number of patients with Child-Pugh class A quickly was increased, while the number of patients with Child-Pugh class B and C was quickly decreased, especially, there was no patients with Child-Pugh class C after 12nd month of follow-up (Figure 5B). Therefore, compared with non-UC-MSCs transplanted patients, UC-MSCs transplantation potently improved liver cirrhosis in ELSD patients.
Complications analysis of patients with UC-MSCs transplantation
The complications of ELSD patients treated with UC-MSCs transplantation was performed in the study. As show in Figure 6, it was found that 9 patients showed upper gastrointestinal bleeding; two patients developed into hepatorenal syndrome; two patients were observed to be hepatic encephalopathy; three patients developed into portal thrombosis; two patients showed hypohepatia; most of patients (28) had no serious complications. Therefore, the complication analysis of UC-MSCs transplantation indicated that this technology treating ELSD patients was relatively safe.