Objective To investigate the immunological rejection after hepatocyte transplantation for acute liver failure （ALF） in mice．Methods The hepatocytes were isolated from pig，BALB/c and C57BL/6 mice livers were conducted and then transplanted into C57BL/6 mice．CCl4 was used to make ALF mice model．The experimental animals were randomly divided into three groups， including syngenic group，allogeneic group，and xenogenic group．The survival statuses of all the mice were recorded. The alteration of T lymphocyte subsets，immune globulin，and cytokine were determined．Results ①The survival ratio was 8/10，6/10， and 3/10 in the syngenic group， allogeneic group， and xenogenic group， respectively．The survival ratio in the syngenic group was significantly higher than that in the other two groups （P＜0.05）．②The CD4+ and CD8+ T cells of the peripheral blood in the syngenic group did not change significantly on week one after transplantation．The CD4+ T cells in the allogeneic group reached the peak on day 3 after hepatocyte transplantation （P＜0.05）， while CD8+ T cells did not change much in one week．The CD4+ and CD8+ T cells in the xenogenic group increased and reached the peak on day 3 after transplantation （P＜0.05）．③There were no significantly differences of IgM and IgG in the syngenic group among 0.5， 1， and 3 d after transplantation. IgM of the allogeneic group and xenogenic group reached the peak on day 1 （P＜0.05） and IgG reached the peak on day 3 （P＜0.05） after transplantation．④The concentrations of IFN-γ， TNF-ɑ， and IL-2 in the allogeneic group and xenogenic group were significantly higher than those in the syngenic group （P＜0.05）．The concentration of IL-6 of the xenogenic group was higher than that of the other two groups （P＜0.05）. Conclusions CD4+ and CD8+ T cells play an important role in immune response to both allogeneic and xenogenic hepatocyte transplantation， as well as induce humoral immune response early after hepatocyte transplantation．
Objective To investigate the effect of ABO-incompatible liver transplantation on patients with acute hepatic failure. Methods A retrospective review was undertaken on the clinical data of 3 cases （1 case of Budd-Chiari syndrome, 1 case of liver cancer and 1 case of severe hepatitis B were included） undergoing ABO-incompatible liver transplantation for acute hepatic failure. The patients were given quadruple immunosuppression after operation. Results Postoperative complications including pulmonary infection, central pontine myelionlysis and acute rejection was suffered from by the patient of Budd-Chiari syndrome who was then given a positive deal and had survived for more than 14 months. The patient of liver cancer was aggravated by severe infection who died of multiple organ failure on day 13 after operation. The patient with severe hepatitis B was made more severe by acute renal failure whose kidney function was restored with continuous renal replacement therapy. Conclusion The outcome of ABO-incompatible liver transplantation can be improved with refined peri-transplant management and better immunosuppressive strategies. ABO-incompatible liver transplantation should be viewed as an important option in patients with acute hepatic failure awaiting an emergency procedure.
ObjectiveTo learn the outcomes of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) cases after artificial liver support system (ALSS) treatment and the relevant factors correlated with the clinical outcomes. MethodsIn the period from January 2011 to June 2014, 321 patients with HBV-ACLF were admitted to West China Hospital. The clinical data at baseline, before and after treatment were analyzed by univariate and multivariate logistic regressions to identify the independent risk factors correlated with 30-day outcomes. ResultsOf all the 321 patients, 233 survived and 88 died by the end of a 30-day observation. The univariate analysis identified that the incidences of cirrhosis, hepatorenal syndrome and peritonitis in the death group were significantly higher (P<0.05). The model for end-stage liver disease values, white blood cells (WBC), blood ammonia, creatinine and total bilirubin (TBIL) at different stages in the death group were significantly higher than those in the survival group (P<0.05). In the death group, the HBV-DNA, TBIL decrease after triple ALSS treatments, baseline prothrombin time activity (PTA) and PTA level after triple ALSS treatments were significantly lower (P<0.05). The multivariate logistic regression indicated that WBC (OR=2.337, P<0.001) and TBIL level after triple ALSS treatments (OR=4.935, P<0.001) were independent predicting factors for death within 30 days after ALSS treatment; HBV-DNA (OR=0.403, P<0.001), the decrease of TBIL after triple ALSS treatments (OR=0.447, P<0.001) and PTA level after triple ALSS treatments (OR=0.332, P<0.001) were protecting factors for the 30-day prognosis. ConclusionThese five factors including WBC, HBV-DNA, PTA, TBIL and TBIL decrease after triple ALSS treatments influence the short-term prognosis for HBV-ACLF patients, which are valuable for decision making in clinical practices.
ObjectiveTo evaluate the therapeutic effect of transplantation of mesenchymal stem cells(MSCs) through the spleen for acute live failure in rat, and to observe migration of transplanted MSCs in vivo. MethodsOne male SD rat was sacrificed to collect MSCs, and MSCs were isolated, expanded, and purified by density gradient centrifugation combined with adhere culture method. The surface antigen expressions of MSCs in the fourth generation were detected by immunohistochemistry method. Twenty-four female rats were given D-galactosamine and tumor necrosis factor α(TNF-α) to establish models of acute liver failure, and then divided into experimental group and blank control group, each group enrolled 12 rats. MSCs of male rat were transplanted into the spleen of female acute liver failure rats in experimental group at 24 hours after model establishment, but rats of blank control group were injected saline(0.5 mL). After the MSCs transplantation, blood samples of rats in 2 groups were got to test levels of serum alanine aminotransferase (ALT), total bilirubin(TBIL), and albumin(ALB). PCR method was used to determine the expression of sex determining region Y gene(SRY gene), and HE staining was used to observe the pathological change of liver tissues of rats in 2 groups. ResultsThe MSCs of the fourth generation expressed CD44 and CD29, but didn't express CD34. There were 5(41.7%) and 3 rats(25.0%) survived at 72 hours, in 1 week and 2 weeks after MSCs transplantation in experimental group and blank control group, respectively, and the survival rate was higher in experimental group(P<0.05). The expression of SRY mRNA was detected in rats of experimental group, as well as the damage of liver tissues in rats of experimental group improved. Compared with blank control group, the levels of ALT and TBIL were lower in experimental group at all time points after MSCs transplantation(P<0.05), but in 1 week and 2 weeks after MSCs transplantation, the levels of ALB in experimental group were higher(P<0.05). ConclusionMSCs can migrate to liver tissue, settle down, and exert the function of replacing hepatocyte after it has been transplanted into the spleen.
Objective To investigate effect of bone marrow mesenchymal stem cells (BMSCs) via portal vein injection on transforming growth factor-β receptor 1 (TGF-βR1) and TGF-βR2 in rats with acute liver failure (ALF). Methods Sixty male SD rats were randomly divided into a normal control group, ALF model group, and BMSCs treatment group, with 20 rats in each group. The rats of normal control group were directly sacrificed without other treatment. The ALF models were made in the rats of BMSCs treatment group and ALF model group, then were treated with BMSCs and equal volume of normal saline respectively. On day 7 after treatment, the 1-week survival situation of rats was observed, the pathological change was observed by HE staining, the apoptosis of liver cells was detected by TUNEL method, and the TGF-βR1 and TGF-βR2 proteins expressions were detected by Western blot method. Results ① The 1-week survival rate of the BMSCs treatment group was significantly higher than that of the ALF model group (P<0.05). ② In the ALF model group, the liver cells were diffuse necrosis, the lobular structure was indistinct, and a large number of bridging necrosis. In the BMSCs treatment group, the infiltrations of inflammatory cells were decreased, and the structure of hepatic lobules gradually recovered, and the normal hepatocytes were seen around it. ③ The apoptosis indexes of the BMSCs treatment group and the ALF model group were significantly higher than those in the normal control group (P<0.05), which in the BMSCs treatment group was significantly lower than that of the ALF model group (P<0.05). ④ The TGF-βR1 and TGF-βR2 proteins expressions in the liver tissues of the ALF model group were significantly higher than those of the normal control group (P<0.05), which of the BMSCs treatment group were significantly lower than those of the ALF model group (P<0.05). Conclusion BMSCs could inhibit apoptosis of hepatocytes in ALF. Its mechanism might be related to expressions of TGF-βR1 and TGF-βR1 proteins, but its specific regulatory pathway needs to be further studied.