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．
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.
ObjectiveTo systematically review the efficacy and safety of plasma exchange (PE) versus routine medical therapy (RMT) for patients with chronic liver failure. MethodsWe electronically searched databases including PubMed, The Cochrane Library (Issue 7, 2014), CBM, CNKI, and VIP from inception to August 2014, to collect randomized controlled trials (RCTs) and clinical controlled trials (CCTs) of PE versus RMT for chronic liver failure patients. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.0 software. ResultsA total of 7 RCTs and 9 CCTs involving 1 632 patients (822 in the PE group and 810 in the RMT group) were included. The results of meta-analysis showed that:compared with the RMT group, the PE group had lower mortality rate (RCT:OR=0.24, 95%CI 0.13 to 0.43; CCT:OR=0.48, 95%CI 0.30 to 0.78) and higher total effective rate (RCT:OR=4.04, 95%CI 2.80 to 5.85; CCT:OR=3.45, 95%CI 2.11 to 5.64). Subgroup analysis based on the stage of liver failure showed that the PE group was superior to the RMT group in early- and intermediate-stage patients with liver failure in total effective rate (early stage:OR=4.78, 95%CI 1.87 to 12.23; intermediate stage:OR=4.43, 95%CI 1.77 to 11.08), but this difference was not found in advanced liver failure patients (OR=1.61, 95%CI 0.35 to 7.38). Seven studies reported 187 cases of adverse reactions (11.46%), and most of them were pruritus and urticaria. ConclusionCurrent evidence shows, compared with the routine medical therapy, the PE therapy could be effective to early- and intermediate-stage liver failure patients, but not be effective to advanced liver failure patients. In addition, patients who received the PE therapy have risks of adverse reactions which mainly are allergic reaction. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
ObjectiveTo summarize the changes and mechanism of related genes induced by stem cell therapy in acute-on-chronic liver failure (ACLF) in recent years, and in order to guide the clinical value of ACLF and curative effect evaluation. MethodsThrough searching Wanfang med, CNKI, Pubmed database and so on in recent years, the differentially expressed genes induced by stem cell therapy for ACLF in recent years was retrieved and the changes of related genes induced during the treatment process were discussed. ResultsBoth at home and abroad had reported that stem cell therapy in the process of ACLF caused mir-27b, TRAIL, and Tg737 genetic changes, some genetic changes had an fixed change trend. ConclusionsStem cells in the treatment of ACLF, cause mir-27b, TRAIL, Tg737 genetic changes, which can provides a new way and method for monitoring stem cell therapy ACLF.
ObjectiveTo summarize the definitions, risk factors, and preoperative evaluation methods of posthe-patectomy liver failure. MethodsDomestic and international publications involving posthepatectomy liver failure were retrieved and reviewed. ResultsThere was no uniform definition of posthepatectomy liver failure, however, the most approbatory definitions were "50-50 criteria" and "International Study Group of Liver Surgery (ISGLS) criteria". Risk factors of posthepatectomy liver failure included patient-related factors, liver-related factors, and surgery-related factors, and preoperative evaluation was mainly based on liver function and liver volume. ConclusionPosthepatectomy liver failure is the main cause of postoperative death, sufficient preoperative evaluation and effective measures to decrease intraoperative blood loss and shorten surgery duration are helpful to prevent and (or) reduce posthepatectomy liver failure.
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.
Objective To explore favorable factors of reducing incidence of postoperative liver failure after radical resection of Bismuth-Corlette type Ⅳ hilar cholangiocarcinoma in condition of hyperbilirubinemia. Methods All the clinical data of one patient with Bismuth-Corlette type Ⅳ hilar cholangiocarcinoma underwent radical resection in June 2017 in the West China Hospital of Sichuan University were collected. The preoperative total bilirubin level of this patient was 470.3 μmol/L, the patient didn’t receive preoperative biliary drainage. The preoperative jaundice time and cholangitis were calculated accurately. A 3D imaging system for quantitative evaluation of the liver was used to reconstruct the images with contrast-enhanced CT images of this patient. And the total liver volume and the future liver remnant volume (FLRV) were calculated. Finally, 6 months of follow-up were conducted after surgery. Results The exact jaundice time was 20 d and there was no preoperative cholangitis. The postoperative FLRV accounted for about 70%. No postoperative liver failure occurred. No recurrence of tumor and death of patient occurred after 6 months of follow-up. Conclusions Radical resection of hilar cholangiocarcinoma in condition of hyperbilirubinemia is not an absolute contraindication for surgery, but indications should be strictly controlled. For special patient whose jaundice with short duration, no preoperative cholangitis and a high FLRV may be treated with directly radical surgery to prevent for losting the best time of surgery.
ObjectiveTo analyze factors affecting post-hepatectomy liver failure (PHLF) of patients with hepatocellular carcinoma (HCC) and explore value of combining albumin-bilirubin (ALBI) score with standardized future liver remnant (sFLR) in prediction of PHLF.MethodsThe clinical data of patients with HCC underwent curative hepatectomy in the Second and the Fifth Departments of General Surgery of the First Hospital of Lanzhou University from January 2016 to June 2018 were retrospectively reviewed. The risk factors of PHLF were identified through the logistic regression, the area under the receiver operating characteristic curve (AUC) was used to analyze the predictive value of the ALBI score, sFLR, or ALBI score×sFLR.ResultsA total of 72 patients with HCC were enrolled, all of them were the Child-Pugh A grade. The incidence of PHLF was 27.78% (20/72) in these 72 patients with HCC, which was 12.96% (7/54) and 72.22% (13/18) in the 54 patients with ALBI- Ⅰ grade and 18 patients with ALBI- Ⅱ grade respectively, the difference was statistically significant (P<0.001). The results of multivariable analysis of PHLF showed that the PLT (OR=0.030, P=0.018), ALBI grade (OR=11.758, P=0.020), and sFLR (OR=0.835, P=0.003) were identified as the independent predictors of PHLF. The AUC for the ALBI score×sFLR in predicting the PHLF was 0.892, it was greater than that of the ALBI score (AUC=0.799) or the sFLR (AUC=0.773).ConclusionCompared with Child-pugh grade, ALBI grade is more accurate in predicting PHLF of HCC patients, and combining ALBI score with sFLR is better than sFLR or ALBI score alone in predicting PHLF of patients with HCC.