The Relation Between Bone Marrow-derived Stem Cells Spontaneous Mobilization And Prognosis Of Patients With HBV-ACLF

Objective:(1)To investigate the relation between bone marrow-derived stem cells spontaneous mobilization and prognosis of patients with HBV- ACLF. Analyse the predictive factors of bone marrow-derived stem cells spontaneous mobilization. Compare the level of bone marrow-derived stem cells of peripheral blood among patients with HBV-ACLF, chronic hepatitis B,chronic hepatitis B virus carrier.(2)To investigate the effect of G-CSF for bone marrow-derived stem cells mobilization and the relationship with prognosis through randomized controlled clinical studies. Further validate the relationship between spontaneous mobilization of bone marrow-derived stem cells and the prognosis of patients with HBV- ACLF.Methods:(1)126 patients with HBV- ACLF, 48 patients undergoing chronic hepatitis B(CHB), and 52 chronic HBV carriers were enrolled.Selected 66 cases randomly from the 126 patients with HBV-related ACLF,clinical data, blood biochemistry, HBV virological indicators and thin peripheral blood CD34+ cell count of patients were collect, using multiariable Logistic regression to analyze the influence factors of concentration of CD34+ cells count,and 66 patients with HBV-ACLF were stratified by CD34 + cell count, compare the difference of the prognosis between groups by survival analysis. With P< 0.05 was considered statistically significant.(2)The above 66 patients with HBV-ACLF as control group, another 60 patients with HBV- ACLF as treatment group. The control group received comprehensive medical treatment, in addition to the comprehensive medical treatment, but also the addition of G-CSF treatment in treatment group. G-CSF treatment of 15?g/Kg/d, subcutaneously, continuously for 6 days after the diagnosis of liver failure.Results:(1) The average age of 66 cases of HBV-ACLF patients in the control group was 46.5(10) years, 54 patients were males(81.8%), 12 patients were females(18.2%), provide comprehensive medical treatment to all of them. The average age of 48 chronic hepatitis B patients was 43(23) years, including 30 males(62.5%) and 18 females(37.5%), provide comprehensive medical treatment to all of them,there was no significant difference between the male and female(?2= 5.435,P=0.066); The average age of 52 chronic HBV carriers was 43(22) years, including 39 males(75%) and 13 females(25%), without treatment,there was no significant difference among three kinds of patients(H=0.541,P=0.763); The averages of baseline peripheral blood CD34 cell count(/?l) of three sets were 2.36(2.6), 1.69(0.76), 0.71(0.98), the most is HBV-ACLF group, the second is chronic hepatitis B group, the results of univariate analysis is that there was significant difference among the three kinds of patients(H = 78.353, P <0.001).(2) 30 cases of the control group were death(45.5%), including 24 males(80%), 6 females(20%), there was no significant difference between the male and female(?2= 0.122,P=0.727). The average age of dead patients was 43(14) years, the average age of survived patients was 43(13) years, there was no significant difference between the average age of two groups(Z =-0.733, P = 0.464). The average MELD score of dead patients was 26.28(3.09), the average MELD score of survived patients was 25.77(3.19), there was no significant difference between the average MELD score of two groups(Z =-1.065, P = 0.287). The average CD34 cell count of dead patients was 1.36(1.63), the average CD34 cell count of survived patients was 2.71(3.17), the results of univariate analysis is that there was significant difference between dead patients and survived patients(Z =-2.391, P =0.017).(3) Linear regression?multiple linear regression were used to analyze the impact of clinical data, clinical examination to the mobilization of bone marrow derived stem cells of 66 HBV-ACLF patients, the results showed that ALT(B=-0.244, P<0.001), ALT/AST(B=-0.364, P<0.001), AFP(B=-0.248, P=0.006), AMY(B=0.681, P<0.001), TG(B=0.578, P<0.001), CHE(B=0.16, P=0.04), INR(B=-0.173, P=0.002), WBC(B=0.373, P<0.001) are statistically significant variable, R2= 0.843.(4) Using chi-square test or non-parametric tests to analyze the gender(?2=0.067,P=0.795), age(Z=-1.762, P=0.787), baseline CD34+cell count(Z =-1.467, P= 0.142) and MELD score(Z=-1.857, P=0.063) between control group and treatment group, there was no significant difference between two groups; CD34+ cell count peak of treatment group is 3.0(1.45)/?l, is higher than control group 1.86(2.58) /?l, the difference was statistically significant(Z=-2.385, P=0.017).(5) Till follow-up finished, there are 30 cases(45.5%) died in the control group, 20 cases(33.3%) in treatment group, the results of survival curves Log Rank test showned Log Rank=4.101, P=0.043, the area under the curve of treatment group is larger than control group, the treatment group which used G-CSF to mobilize bone marrow stem cell had higher survival rates than control group, the difference was statistically significant.Conclusion:(1) HBV-ACLF patients can spontaneously mobilize bone marrow-derived stem cells to improve liver function, the level of spontaneous mobilization is positively correlated with prognosis.(2) Bone marrow-derived stem cells spontaneous mobilization leve of HBV-ACLF patients in control group is higher than that in chronic hepatitis and chronic HBV carriers group, mobilization level was positively correlated with the degree of liver damage.(3) ALT, ALT/AST, AFP, INR were negatively correlated with bone marrow derived stem cells spontaneous mobilization, AMY, TG, CHE, WBC were were positively with bone marrow derived stem cells spontaneous mobilization.(4) G-CSF can enhance bone marrow-derived stem cells mobilize level in HBV-ACLF patients, and can improve survival.