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 summarize present situation and development of non-biological artificial liver. Method The related literatures about artificial liver treatment in recent years were reviewed. Results The current artificial liver which applied to clinic mainly are non-biological artificial liver, including plasma exchange, hemodialysis, hemofiltration, bilirubin adsorption, hemoperfusion, molecular adsorption recycling, etc. Because of the individual clinical cases, the individualized requirements for treatment are put forward. Single treatment of non-biological artificial liver is often unable to satisfy the individualized requirements, combined the advantages of each treatment so as to maximum therapeutic effect for patients has become a trend. Conclusion Combined treatment of non-biological artificial liver is superior to single treatment, individual treatment concept should be carried out in whole process of treatment.
Extensive hepatectomy can achieve a higher chance of radical resection of lesions in the hepatobiliary system, but the risk of fatal complications of severe liver failure after surgery also increases accordingly. Therefore, enhancing the liver’s regenerative capacity has always been a hot topic in clinical research. Portal vein blood supply is of great significance for maintaining the normal function of the liver and promoting the repair and proliferation of damaged liver tissue. After selectively altering the blood flow distribution in the portal vein, atrophy or proliferation will occur in different liver lobes. The discovery of the important physiological phenomenon of liver regeneration induced by deportalized blood flow of portal vein has made it possible to promote the volume growth and functional enhancement of the residual liver lobes before hepatectomy, and various technical schemes have been applied and developed in clinical practice. The interim research results show that the portal vein embolization technique is mature, has less trauma, but the induction speed is relatively slow. Portal vein combined with hepatic vein embolization has better induction efficacy and does not increase embolism-related complications, and has a wider range of applications. The induction ability of associating liver partition and portal vein ligation for staged hepatectomy is significant, but the surgical trauma is large, and there are higher requirements for perioperative management. There is a clear correlation between high surgical volume centers and technical improvements and a significant reduction in complications. Resection and partial liver transplantation with delayed total hepatectomy not only break through the bottlenecks of safety and ethical requirements for living donor liver transplantation in adults, but also innovate and enrich the second-stage extensive hepatectomy schemes. However, their technical standards and application scope still need more high-quality research evidence to support them.
ObjectiveTo retrospective analysis the research progress of the acute-on-chronic liver failure (ACLF), and provide some useful advice for the early diagnosis, evaluation, and treatments of ACLF. MethodsThe literatures on ACLF which published in domestic and overseas for these years were reviewed. ResultsACLF, which is an acute deterioration of liver function results from precipitating events in patients with chronic liver disease. As an independent clinical entity and different from acute liver failure (ALF), sub-acute liver failure (SALF), and chronic liver failure (CLF). For the high short-term mortality and seldom good treatment measures, attached much people's attention. ConclusionThe research of ACLF makes great advance but still exits different in some field between the East and the West. Search dangerous etiology earlier, combine with reality and early effective treatments can develop total survival rate of ACLF.
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 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.
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 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.
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．