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Objective:To explore the long-term therapeutic efficacy and outcomes of liver transplantation for patients with hepatic myelopathy (HM).Methods:Retrospective analysis of 24 adult liver transplantation recipients due to HM at First Central Municipal Hospital from January 2006 to October 2022. HM was extensively classified by the severity of lower extremity symptoms, degree of muscle stiffness, capability for independent ambulation and muscle strength. Furthermore, their long-term outcomes were examined. From January 2000 to October 2022, the databases of China National Knowledge Infrastructure (CNKI) , Google Scholar, PubMed and Web of Science were searched with such keywords as "肝性脊髓病and肝移植" "Hepatic Myelopathy and Liver Transplantation" .Results:After liver transplantation, liver functions and blood ammonia normalized and most clinical symptoms improved. During a follow-up period of (12-190) months, 19 patients showed a lowered grade of HC as compared to pre-transplantation. Four cases achieved a complete recovery of extremity function. No change occurred in severity grade for the remaining 5 patients. However, 4 of them experienced varying degrees of improvement in muscle strength and independent walking capability. This review summarized the clinical characteristics and clinical outcomes of 17 patients from both domestic and international sources. Most of them experiences varying degrees of symptomatic improvements after liver transplantation (16 cases).Conclusions:This study has confirmed the effectiveness of liver transplantation for HM and its contribution to the long-term patient recovery.
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Objective:To explore the feasibility and safety of robotic-assisted living donor left lateral segmentectomy (LDLLS) in a large pediatric liver transplant program.Methods:Retrospective analysis was performed for clinical data of 45 LDLLS donors and recipients from June 2021 to September 2022.Traditional open donor liver resection (n=30) and robotic-assisted segmentectomy (n=15) were performed.Two groups were compared with regards to operative duration, intraoperative hemorrhage, postoperative healing and postoperative complications.SPSS 21.0 was utilized for statistical analysis.Independent sample T, paired sample T, Wilcoxon rank sum and Chi-square tests were performed for examining the inter-group differences.Results:Operative duration of robot-assisted surgery group was substantially longer than that of traditional open surgery group ( P<0.001). Intraoperative blood loss was less in robot-assisted surgery group was less than that in traditional open surgery group[(106.0±39.8) vs.(251.0±144.8) ml, P=0.001]. Postoperative hospital stay of robot-assisted surgery group was shorter than that of traditional open surgery group[6.0(6.0, 6.0) vs.7.0(6.0, 9.0), P<0.05]. Two cases of postoperative biliary leakage were observed in donor of traditional open surgery group.Among 2 cases of abdominal infection, one was due to biliary leakage from liver section and secondary surgery was then performed.One case of incisional infection and another case of thrombosis occurred in donor of traditional open surgery group.In robot-assisted surgery group, only one donor had amylase elevation.In traditional open surgery group, there were one case of local thrombosis in middle hepatic vein and one case of bile duct stricture.No long-term complications occurred in robot-assisted surgery group during a follow-up period of over 6 months.Finally recipient data analysis indicated that no significant inter-group differences existed in operative duration, intraoperative blood loss, postoperative hospital stay or postoperative abdominal infection ( P=0.634, P=0.180, P=0.86 and P=0.153). Conclusions:Robotic-assisted LDLLS proves to be be a safe and reliable option for living donor segmentectomy.It is superior to conventional LDLLS in terms of shorter hospital stay, less intraoperative blood loss and fewer postoperative complications.
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Objective To evaluate the role of preoperative serological indexes in predicting long-term survival and tumor recurrence of hepatocellular carcinoma (HCC) patients after liver transplantation, aiming to explore its significance in expanding the Milan criteria. Methods Clinical data of 669 recipients undergoing liver transplantation for HCC were retrospectively analyzed. The optimal cut-off value was calculated by the receiver operating characteristic (ROC) curve. The risk factors affecting the overall survival and recurrence-free survival rates of HCC patients after liver transplantation were identified by univariate and multivariate regression analyses. The correlation between preoperative serum liver enzymes and pathological characteristics in HCC patients was analyzed. The predictive values of alpha-fetoprotein (AFP) combined with γ -glutamyl transferase (GGT) and different liver transplant criteria for the survival and recurrence of HCC patients after liver transplantation were compared. Results Exceeded Milan criteria, total tumor diameter (TTD) > 8 cm, AFP > 200 ng/mL and GGT > 84 U/L were the independent risk factors for the overall survival and recurrence-free survival rates of HCC patients after liver transplantation (all P < 0.05). Correlation analysis showed that preoperative serum GGT level was correlated with TTD, number of tumor, venous invasion, microsatellite lesions, capsular invasion, tumor, node, metastasis (TNM) stage, Child-Pugh score and exceeded Milan criteria (all P < 0.05). Milan-AFP-GGT-TTD (M-AGT) criteria were proposed by combining Milan criteria, TTD with serum liver enzyme indexes (AFP and GGT). The 5-year overall survival and recurrence-free survival rates of HCC recipients who met the M-AGT criteria (111 cases of exceeded Milan criteria) were significantly higher than those who met Hangzhou criteria (both P < 0.05), whereas had no significant difference from their counterparts who met the University of California at San Francisco (UCSF) criteria (both P > 0.05). Conclusions Preoperative serological indexes of AFP and GGT could effectively predict the long-term survival and tumor recurrence of HCC patients after liver transplantation. Establishing the M-AGT criteria based on serological indexes contributes to expanding the Milan criteria, which is convenient and feasible.
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Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA. 5. Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such convergent evolution and its impact on humoral immunity remain unclear. Here, we demonstrate that these convergent mutations can cause striking evasion of neutralizing antibody (NAb) drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2 binding capability. BQ.1.1.10, BA.4.6.3, XBB, and CH. 1.1 are the most antibody-evasive strain tested, even exceeding SARS-CoV-1 level. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from BA.2 and BA.5 breakthrough-infection convalescents. Importantly, due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection caused significant reductions in the epitope diversity of NAbs and increased proportion of non-neutralizing mAbs, which in turn concentrated humoral immune pressure and promoted convergent evolution. Moreover, we showed that the convergent RBD mutations could be accurately inferred by integrated deep mutational scanning (DMS) profiles, and the evolution trends of BA.2.75/BA.5 subvariants could be well-simulated through constructed convergent pseudovirus mutants. Together, our results suggest current herd immunity and BA.5 vaccine boosters may not provide good protection against infection. Broad-spectrum SARS-CoV-2 vaccines and NAb drugs development should be highly prioritized, and the constructed mutants could help to examine their effectiveness in advance.
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SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility over BA.21. The new variants receptor binding and immune evasion capability require immediate investigation. Here, coupled with Spike structural comparisons, we show that BA.2.12.1 and BA.4/BA.5 exhibit comparable ACE2-binding affinities to BA.2. Importantly, BA.2.12.1 and BA.4/BA.5 display stronger neutralization evasion than BA.2 against the plasma from 3-dose vaccination and, most strikingly, from post-vaccination BA.1 infections. To delineate the underlying antibody evasion mechanism, we determined the escaping mutation profiles2, epitope distribution3 and Omicron neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype-induced humoral memory. The resulting elicited antibodies could neutralize both wildtype and BA.1 and are enriched on non-ACE2-competing epitopes. However, most of these cross-reactive NAbs are heavily escaped by L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1; nevertheless, these NAbs are largely escaped by BA.2/BA.4/BA.5 due to D405N and F486V, and react weakly to pre-Omicron variants, exhibiting poor neutralization breadths. As for therapeutic NAbs, Bebtelovimab4 and Cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
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BackgroundSARS-CoV-2 Omicron variant BA.1 first emerged on the Chinese mainland in January 2022 in Tianjin and caused a large wave of infections. During mass PCR testing, a total of 430 cases infected with Omicron were recorded between January 8 and February 7, 2022, with no new infections detected for the following 16 days. Most patients had been vaccinated with SARS-CoV-2 inactivated vaccines. The disease profile associated with BA.1 infection, especially after vaccination with inactivated vaccines, is unclear. Whether BA.1 breakthrough infection after receiving inactivated vaccine could create a strong enough humoral immunity barrier against Omicron is not yet investigated. MethodsWe collected the clinical information and vaccination history of the 430 COVID-19 patients infected with Omicron BA.1. Re-positive cases and inflammation markers were monitored during the patients convalescence phase. Ordered multiclass logistic regression model was used to identify risk factors for COVID-19 disease severity. Authentic virus neutralization assays against SARS-CoV-2 wildtype, Beta and Omicron BA.1 were conducted to examine the plasma neutralizing titers induced after post-vaccination Omicron BA.1 infection, and were compared to a group of uninfected healthy individuals who were selected to have a matched vaccination profile. FindingsAmong the 430 patients, 316 (73.5%) were adults with a median age of 47 years, and 114 (26.5%) were under-age with a median age of 10 years. Female and male patients account for 55.6% and 44.4%, respectively. Most of the patients presented with mild (47.7%) to moderate diseases (50.2%), with only 2 severe cases (0.5%) and 7 (1.6%) asymptomatic infections. No death was recorded. 341 (79.3%) of the 430 patients received inactivated vaccines (54.3% BBIBP-CorV vs. 45.5% CoronaVac), 49 (11.4%) received adenovirus-vectored vaccines (Ad5-nCoV), 2 (0.5%) received recombinant protein subunit vaccines (ZF2001), and 38 (8.8%) received no vaccination. No vaccination is associated with a substantially higher ICU admission rate among Omicron BA.1 infected patients (2.0% for vaccinated patients vs. 23.7% for unvaccinated patients, P<0.001). Compared with adults, child patients presented with less severe illness (82.5% mild cases for children vs. 35.1% for adults, P<0.001), no ICU admission, fewer comorbidities (3.5% vs. 53.2%, P<0.001), and less chance of turning re-positive on nucleic acid tests (12.3% vs. 22.5%, P=0.019). For adult patients, compared with no prior vaccination, receiving 3 doses of inactivated vaccine was associated with significantly lower risk of severe disease (OR 0.227 [0.065-0.787], P=0.020), less ICU admission (OR 0.023 [0.002-0.214], P=0.001), lower re-positive rate on PCR (OR 0.240 [0.098-0.587], P=0.002), and shorter duration of hospitalization and recovery (OR 0.233 [0.091-0.596], P=0.002). At the beginning of the convalescence phase, patients who had received 3 doses of inactivated vaccine had substantially lower systemic immune-inflammation index (SII) and C-reactive protein than unvaccinated patients, while CD4+/CD8+ ratio, activated Treg cells and Th1/Th2 ratio were higher compared to their 2-dose counterparts, suggesting that receipt of 3 doses of inactivated vaccine could step up inflammation resolution after infection. Plasma neutralization titers against Omicron, Beta, and wildtype significantly increased after breakthrough infection with Omicron. Moderate symptoms were associated with higher plasma neutralization titers than mild symptoms. However, vaccination profiles prior to infection, whether 2 doses versus 3 doses or types of vaccines, had no significant effect on post-infection neutralization titer. Among recipients of 3 doses of CoronaVac, infection with Omicron BA.1 largely increased neutralization titers against Omicron BA.1 (8.7x), Beta (4.5x), and wildtype (2.2x), compared with uninfected healthy individuals who have a matched vaccination profile. InterpretationReceipt of 3-dose inactivated vaccines can substantially reduce the disease severity of Omicron BA.1 infection, with most vaccinated patients presenting with mild to moderate illness. Child patients present with less severe disease than adult patients after infection. Omicron BA.1 convalescents who had received inactivated vaccines showed significantly increased plasma neutralizing antibody titers against Omicron BA.1, Beta, and wildtype SARS-CoV-2 compared with vaccinated healthy individuals. FundingThis research is supported by Changping Laboratory (CPL-1233) and the Emergency Key Program of Guangzhou Laboratory (EKPG21-30-3), sponsored by the Ministry of Science and Technology of the Peoples Republic of China. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPrevious studies (many of which have not been peer-reviewed) have reported inconsistent findings regarding the effect of inactivated vaccines against the Omicron variant. On Mar 6, 2022, we searched PubMed with the query "(SARS-CoV-2) AND ((Neutralisation) OR (Neutralisation)) AND ((Omicron) OR (BA.1)) AND (inactivated vaccine)", without date or language restrictions. This search identified 18 articles, of which 13 were directly relevant. Notably, the participants in many of these studies have received only one or two doses of inactivated vaccine with heterologous booster vaccination; other studies have a limited number of participants receiving inactivated vaccines. Added value of this studyTo date, this is the first study to report on the protective effect of inactivated vaccines against the severe disease caused by the Omicron variant. We examine and compare the disease profile of adults and children. Furthermore, we estimate the effect of post-vaccination omicron infection on plasma neutralization titers against Omicron and other SARS-COV-2 variants. Specifically, the disease profile of Omicron convalescents who had received two-dose primary series of inactivated vaccines with or without a booster dose prior to infection is compared with unvaccinated patients. We also analyzed the effect of infection on neutralizing activity by comparing vaccinated convalescents with vaccinated healthy individuals with matched vaccination profiles. Implications of all the available evidenceCompared with adults, child patients infected with Omicron tend to present with less severe disease and are less likely to turn re-positive on nucleic acid tests. Receipt of two-dose primary series or three doses of inactivated vaccine is a protective factor against severe disease, ICU admission, re-positive PCR and longer hospitalization. The protection afforded by a booster dose is stronger than two-dose primary series alone. Besides vaccination, infection with Omicron is also a key factor for elevated neutralizing antibody titers, enabling cross-neutralization against Omicron, wildtype (WT) and the Beta variant.
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Omicron sub-lineage BA.2 has rapidly surged globally, accounting for over 60% of recent SARS-CoV-2 infections. Newly acquired RBD mutations and high transmission advantage over BA.1 urge the investigation of BA.2s immune evasion capability. Here, we show that BA.2 causes strong neutralization resistance, comparable to BA.1, in vaccinated individuals plasma. However, BA.2 displays more severe antibody evasion in BA.1 convalescents, and most prominently, in vaccinated SARS convalescents plasma, suggesting a substantial antigenicity difference between BA.2 and BA.1. To specify, we determined the escaping mutation profiles1,2 of 714 SARS-CoV-2 RBD neutralizing antibodies, including 241 broad sarbecovirus neutralizing antibodies isolated from SARS convalescents, and measured their neutralization efficacy against BA.1, BA.1.1, BA.2. Importantly, BA.2 specifically induces large-scale escape of BA.1/BA.1.1-effective broad sarbecovirus neutralizing antibodies via novel mutations T376A, D405N, and R408S. These sites were highly conserved across sarbecoviruses, suggesting that Omicron BA.2 arose from immune pressure selection instead of zoonotic spillover. Moreover, BA.2 reduces the efficacy of S309 (Sotrovimab)3,4 and broad sarbecovirus neutralizing antibodies targeting the similar epitope region, including BD55-5840. Structural comparisons of BD55-5840 in complexes with BA.1 and BA.2 spike suggest that BA.2 could hinder antibody binding through S371F-induced N343-glycan displacement. Intriguingly, the absence of G446S mutation in BA.2 enabled a proportion of 440-449 linear epitope targeting antibodies to retain neutralizing efficacy, including COV2-2130 (Cilgavimab)5. Together, we showed that BA.2 exhibits distinct antigenicity compared to BA.1 and provided a comprehensive profile of SARS-CoV-2 antibody escaping mutations. Our study offers critical insights into the humoral immune evading mechanism of current and future variants.
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Acute-on-chronic liver failure (ACLF) is a disease of rapid deterioration of liver function caused by the acute exacerbation of chronic liver diseases, and it is often associated with multiple organ failure and has a poorer prognosis than common liver cirrhosis. Many studies suggest that timely liver transplantation can significantly improve the survival rate of patients with ACLF; however, there are currently no reliable guidelines that point out the indications for liver transplantation in patients with ACLF. This article summarizes recent studies and discusses the indication, timing, and prognosis of liver transplantation in ALCF patients.
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Objective:To explore the pathogenesis and prognostic factors of brain metastasis of hepatocellular carcinoma(HCC)after liver transplantation(LT).Methods:Retrospective review was performed for 17 HCC cases with brain metastasis after liver transplantation from 2000 to 2020.All cases were diagnosed as hepatitis B cirrhosis complicated with HCC.All of them were beyond the Milan Criteria.The immunosuppressive regimen consisted of baliximab + mycophenolate mofetil + calcineurin inhibitors(CNIs)+ corticosteroids in early postoperative period with a gradual tapering of corticosteroids and mycophenolate mofetil.Three patients received sirolimus immunotherapy after tumor recurrence and withdrew CNIs.One of three cases received sorafenib.Results:Other organ involvements included lung metastasis( n=16, 94.1%), bone metastasis( n=5, 29.4%)and liver metastasis( n=6, 35.3%). The median survival time after brain metastasis was 7 months and the 1-year cumulative survival rate 29.4%.The median survival time post-LT was 14 months and the 1-year cumulative survival rate 64.7%.Among 7 patients with a resection of brain metastasis, two deaths at Month 1 post-operation were due to cerebral hemorrhage.The longest survival time was 214 months and the median survival time 9 months. Conclusions:The prognosis of brain metastasis post-LT remains poor.However, early detection and reasonable treatment can prolong patient survival time and even achieve long-term survival.Most brain metastases are accompanied by lung metastases.And the finding of lung metastatic tumor hints at a presence of intracranial lesions.
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Objective:To compare the treatment outcomes of neoadjoint therapy combined with liver transplantation versus radical hepatectomy for patients with surgically resectable hilar cholangiocarcinoma.Methods:A retrospective study was performed on the data of 64 patients with resectable hilar cholangiocarcinoma operated from January 2009 to December 2014 at the Organ Transplantation Department of the First Central Hospital of Tianjin. There were 43 males and 21 females, with an average age of 61.2 years. There were 45 patients who underwent radical hepatectomy in the liver resection group, and 19 patients who underwent combined neoadjuvant therapy (radiotherapy combined with 5-fluorouracil intravenous drip, transcatheter lumen radiotherapy, capecitabine oral administration) and liver transplantation in the liver transplantation group. The recurrence rates and survival rate were compared between groups.Results:The 1, 3 and 5 years cumulative survival rates of the liver transplantation group were 89.5%, 73.7% and 63.2%, respectively, which were significantly better than those of the liver resection group (80.0%, 53.3% and 35.6%) ( P<0.05). The postoperative tumor recurrence rate in the liver transplantation group was 31.6% (6/19), which was significantly lower than that in the liver resection group of 60.0% (27/45) ( P<0.05). Subgroup analysis using postoperative pathological results showed the cumulative survival rates of patients without lymph node metastasis (N 0) and those with negative resection margins (R 0) were not significantly different between groups ( P>0.05). However, for patients with regional lymph node invasion (N 1) and with R 0 resection margin, the cumulative survival rates at 1, 3 and 5 years after liver transplantation were 83.3%, 66.7% and 50.0%, respectively, which were significantly superior to the 64.3%, 28.6% and 14.3% of the liver resection group ( P<0.05). Conclusion:Hepatectomy is recommended for patients with N 0 R 0 resectable hilar cholangiocarcinoma. For patients with hilar cholangiocarcinoma with marginally resectable N 1R 0, neoadjuvant therapy combined with liver transplantation resulted in significantly better long-term overall survival than resection.
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Objective:To explore the clinicalfactors related to allograft fibrosis after pediatric liver transplantation.Methods:The clinical data were respectively analyzed for 94 pediatric recipients from January 2013 to December 2016 at Tianjin First Central Hospital.The Patients were assigned into fibrotic and non-fibrotic groups based upon the results of protocol liver biopsies. Univariate and multivariate Logistic regression analyses were performed for examining the risk factors of fibrosis after pediatric livertransplantation. Then Logistic regression model was established to obtain the predicted value of combined predictive factors.Thereceiver operating characteristic curve (ROC) was conducted to evaluate the predictive value of combined predictive factors.Results:A total number of 54(57.5%) patients occurred fibrosis among the 94 patients. There weresignificant differences in cold ischemia time (Z=2.094), warm ischemia time (Z=2.421), biliary stricture( χ2=4.560), drug-induced liver injury ( χ2=7.389), hepatic artery thrombosis and rejection ( χ2=6.955)between two groups ( P<0.05). Logistic regression analysis showed that cold ischemia time (OR=1.003, 95%CI: 1.000~1.007, P=0.044), biliary stricture(OR=6.451, 95%CI: 1.205~33.295), rejection(OR=2.735, 95%CI: 1.057~7.077)and drug-induced liver injury (OR=4.977, 95%CI: 1.207~20.522, P=0.026) were independent risk factors for fibrosis 5 years after liver transplantation. The area under the ROC curve was 0.786(95%CI: 0.691~0.881), for predicting patient outcome.If using 0.311as a cutoff Value, the sensitivity was 90.70%, and the specificity was 60.00%. However, through the ROC curve comparison, there was statistical significance between combined predictive factors and the other independent risk factors ( P>0.05). Conclusions:The incidence of fibrosis 5 years after pediatricliver transplantation is 57.5%. Prolonged cold ischemia time, biliarystricture, rejectionand drug-induced liver injury after liver transplantation are independent risk factors for fibrosis 5 years after pediatric liver transplantation.And the combined predictive factors have a high predictive value forallograftfibrosis.
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Objective:To Eveluate the safty and clinical efficacy of combined laparoscopic spleen-preserving distal pancreatectomy and autologous islet transplantation in the treatment of solid pseudopapillary neoplasm.Methods:A 22 years old solid pseudopapillary neoplasm female patient who underwent distal pancreatectomy and an autologous islet transplantation at Tianjin First Central Hospital, clinical date for 6 months follow up was collected and analyzed.Results:The patient was well recovered after surgery, and during the post-operative follow up, the fasting blood glucose was 5.72 mmol/L, HbA1c was 6.1%, remained insulin independent, the liver function was kept well.Conclusions:Combined Laparoscopic spleen-preserving distal pancreatectomy and autologous islet transplantation can effectively prevent diabetes after distal pancreatectomy.
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Objective To study the effect of bone marrow mesenchymal stem cells (BMMSCs) combined with normothermic mechanical perfusion (NMP) on biliary epithelial cells (BEC) after DCD donor liver transplantation in rats.Methods The third generation of BMMSCs and the BMMSCs modified by Ad/HO-1 (Ad/HO-1/BMMSCs) were cultured,identified and expanded in vitro.To establish a stable NMP system device in vitro.The DCD liver transplantation models were constructed in rats after cardiac ischemia for 30 minutes,220 SD recipient rats were randomly divided into sham operation group (S group,n=44) static cold storage (SCS group,n =44) group,and simple NMP group (P group,n =44),BMMSCs combined with NMP group (BP group,n =44) and BMMSCs modified by Ad/HO-1 combine with NMP group (HBP group,n =44),NMP group,BP group and HBP group were subjected to vitro perfusion for 4h.The group were taken at 0,1,7 and 14 days after transplantation and the relevant indicators were detected,n =6 in each group.The survival rate of the recipient rats,liver function and pathological changes of the bile duct were observed.The expression of cytokeratin 19 (CK19) protein in BEC was detected by immunohistochemistry and Western blot.Apoptotic biliary epithelial cells were detected by TUNEL staining and the expression of apoptosis-related protein caspase-3 was detected by immunohistochemistry.Results The survival time of HBP group was significantly prolonged for (5.6 ±0.8) d in SCS group vs.(18.4 ±2.0) d in NMP group,(20.5 ± 1.5) d in BP group,(82.5 ±3.2) d in HBP group,the differences were statistically significant (all P ＜ O.05).Compared with other groups,the HBP group and the BP group were significantly improved in liver function and biliary pathology,and the expression of CK19 protein in BEC was significantly increased [(0.81 ±0.02) in S group vs.(0.35 ±0.03) in SCS group,(0.47 ±0.02) in NMP group,(0.63 ± 0.02) in BP group,(0.77 ± 0.01) in HBP group on postoperative day (POD) 14],the differences were statistically significant (all P ＜ 0.05).The number of apoptosis and the expression of apoptosis-related protein caspase-3 in HBP group were significantly decreased [(10.0 ± 1.2) in S group vs.(57.3 ±5.5) in SCS group,(40.1 ±4.6) in NMP group,(32.0 ± 2.2) in BP group,(13.7 ± 3.1) in HBP group on POD 14],the difference was statistically significant (all P ＜ 0.05).Compared with the BP group,the protective effect of the HBP group was more obvious,and the difference was statistically significant (P ＜ 0.05).Conclusion By the method of the BMMSCs modified by Ad/HO-1 combined with NMP in vitro preservation of rat,DCD donor liver can significantly improve the effect of BEC on rats and the survival rate after liver transplantation.
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Liver transplantation is the most effective therapeutic options for the patients at the advanced stage, but with the amount of transplant surgery increasing, margin donors are used for transplantation in the case of severe donor organ deficiency. However, the commonly used cold storage technique has poor preservation effect on margin donors, resulting in an increase in the incidence of complications after transplantation. The donated liver quality is one the most important factors for the patients long term survival, so there is an urgent need for a new type of organ preservation technology to preserve the margin donors in vitro. This paper summarized the current research on the ex-vivo preservation methods of liver and the new mechanical perfusion preservation methods.
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Objective:To explore the role of heme oxygenase-1 (HO-1) modified bone marrow mesenchymal stem cells (BMMSCs) in improving hepatic microcirculation after reduced-size liver transplantation (RLT) in rats.Methods:BMMSCs were isolated and cultured in vitro by adherence method. Then HO-1/adenovirus (Adv) was transfected for constructing HO-1/BMMSCs. The "dual-sleeve" method was employed for establishing an acute rejection model after 50% RLT. Immediately post-operation, 1 ml normal saline (NS) and BMMSCs or HO-1/BMMSCs single cell suspension were injected. The changes of surviving rats were observed by parameters at Day 3/7/14 post-operation. Five rats were observed at each timepoint. The serum level of mitochondrial aspartate aminotransferase (mAST) was detected; Na+ -K+ -ATPase in transplanted liver was measured by chemical colorimetry; mitochondrial ultrastructural changes were observed under a transmission electron microscope. Portal vein pressure was detected by Power Lab at Day 7 post-operation; the expressions of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and von Willebrand factor (vWF) in liver tissues were detected by Western blot. Liver histopathological changes were observed by hematoxylin & eosin stain. The expression of vWF was detected by immunohistochemistry and serum level of hyaluronic acid (HA) detected by enzyme-linked immunosorbent assay (ELISA).Results:HO-1/BMMSCs could significantly lessen the pathological injury and rejection of 50% reduced-size transplanted liver, improve mitochondrial damage and energy metabolism, promote the expression of eNOS, suppress the expression of iNOS, reduce portal pressure, up-regulate the expression of hepatic sinus vWF and HA degradation, protect hepatic sinusoidal endothelial cells (SECs) and ultimately improve hepatic microcirculation. And the differences were statistically significant as compared with NS/BMMSCs group ( P<0.05). Conclusions:HO-1/BMMSCs may play an important role in protecting rat liver by improving hepatic microcirculation during RLT.
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Objective To investigate the clinical efficacy and influencing factors in patients with acute-on-chronic liver failure grade 3 after liver transplantation.Methods 33 patients with acute-on-chronic grade 3 liver failure who were treated in Tianjin First Center Hospital from January 2015 to December 2017 was retrospectively analyzed,including 21 patients in liver transplantation group and 12 patients in control group.Among them,28 patients were males and 5 patients were females,aged (43.4± 12.3) years.The data and follow-up information of all patients were collected.The survival condition was analyzed by Kaplan-Meier.Univariate and multivariate Cox regression analysis was used to analyze the risk factors of death in patients after liver transplantation.Results There was no significant difference in Child-Pugh score,total bilirubin,creatinine and infection before operation between liver transplantation group and control group (P＞0.05).The age of patients in liver transplantation group was older than the control group,the difference was statistically significant (P＜0.05).The 1-year and 3-year cumulative survival rates in the liver transplantation group were 61.9％ and 61.9％ respectively and the rates in control group were 8.3％ and 8.3％ respectively by Kaplan-Meier survival analysis.There was significant difference between the two groups (P＜0.05).Twenty-one patients in the liver transplantation group were followed up for a long time,13 patients survived and followed up for 163～ 1 123 days.Except for renal insufficiency complicated with renal anemia in 1 case,the other 12 cases had normal liver function,and 8 cases died in 2～54 days after liver transplantation.Postoperative shock was an independent risk factor for death after liver transplantation by univariate and multivariate Cox regression analysis.Conclusion Acute-on-chronic grade 3 liver failure was indication for liver transplantation,postoperative shock was an independent risk factor for death after liver transplantation.
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Objective To explore the effect and mechanism of heme oxygenase-1 (HO-1) gene modified bone marrow mesenchymal stem cells (BMMSCs) on rat reduced-size liver transplantation.Methods 50 male Brown Norway (BN) rats were used to prepare BMMSCs.Male Lewis and BN rats were 75,respectively.BN rats were randomly divided into model group (n =25),stem cell group (n =25) and combined group (n =25).Acute rejection models following 50％ reduced-size transplantaton were established in rats using two-cuff technique,1 ml of normal saline,BMMSCs suspension,or HO-1/BMMSCs suspension were injected immediately after surgery.Rats were executed at an instant,3rd,7th and 14th day after surgery to identify BMMSCs and HO-1/adenovirus infection efficiency.Evaluated hepatic pathology by HE staining.Liver function indexes were detected.Portal vein pressure on 7th day after surgery was detected.The levels of endothelin-1 (ET-1) and nitric oxide (NO) in serum were detected using ELISA.The expressions of ET-1 in liver were detected by immunohistochemistry staining and Western blotting.Results High purity BMMSCs were obtained and HO-1/BMMSCs were successfully infected.Compared with model group,liver tissue injury and rejection were alleviated in stem cell group and combined group,liver function was improved,and the combined group was superior to stem cell group.The portal vein pressure in model group,stem cell group,and combined group were 21.3±0.2 mmHg,11.2±0.2 mmHg,and 10.1±0.1 mmHg,respectively.The portal vein pressure in three groups showed a decreasing trend,difference was statistically significant (P＜0.05).On the 3rd,7th and 14th day after surgery,compared with model group,the expression levels of ET-1 and NO in the stem cell group and the combined group were decreased,and the combined group was significantly lower than stem cell group (P＜ 0.05).Conclusion HO-1/BMMSCs improved liver function and portal vein pressure after reduced-size liver transplantation in rats,and may play a protective role by regulating ET-1/NO expression.
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Objective To explore the surgical indications for pancreas-kidney surgery and summarize the experiences of ,selecting surgical approaches ,formulating immunosuppressive regimens and preventing complications .Methods A total of 145 donor simultaneous pancreas-kidney transplants in uremic patients with T1DM/T2DM between 2002 and 2018 were retrospectively analyzed .Based upon surgical approaches and immunosuppressive agents ,they were divided into three eras of 2002-2010 ,2011-2014 and 2015-2018 respectively .Patient profiles ,survival outcomes of patient and graft , surgical techniques ,immunosuppressive agents and incidence of common complications were compared among different groups .Results The overall 1/3/5-year patient and graft survival rates of three groups were above 75％ and the survival rates of group Ⅰ were inferior to those of groups Ⅱ and Ⅲ(P<0 .001) .The overall 1/3/5-year pancreas graft survival rates were the highest in group Ⅲ and the lowest in group Ⅱ (P=0 .004) .In the 2015-2018 group ,ipsilateral pancreas-kidney transplantation and SE-ED surgery were more preferred .Regarding the incidence of complications ,graft thrombosis frequently occurred from 2011 to 2014 and intestinal obstruction was more common from 2002 to 2010 .For univariable analysis of graft loss ,anticoagulation programme with argatroban monohydrate were 0 .28 times likely to lose pancreas graft (OR= 0 .28 ,95％ CI:0 .09-0 .86) and T1DM patients were 4 times likely to have kidney graft loss (OR=4 .08 ,95％ CI:1 .37-12 .15) .Conclusions SPK is an effective treatment for uremic diabetics . Effective perioperative management and preventing complications are crucial for prolonging patient and graft survivals .
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Objective To explore the prognostic role of laminin (LN ) as a tumor biological marker in predicting the recurrence of hepatocellular carcinoma (HCC) related with HBV infection after liver transplantation (LT ) .Methods Tissue samples from 251 HBV-related HCC patients undergoing LT were immunohistochemically stained with anti-LN antibody .The relevant prognostic factors were analyzed using Spearman's rank test , Kaplan-Meier method , log-rank test and multivariate step-wise Cox regression analysis .Results The expressions of LN in tumor tissues were significantly positively correlated with tumor number (P=0 .00) ,microsatellite (P=0 .02) ,venous invasion (P=0 .048) ,pTNM tumor stage (P=0 .00) ,pre-LT serum α-fetoprotein (AFP) level (P=0 .00) ,HBV DNA level (P= 0 .02) ,HBeAg level (P= 0 .02) and tumor recurrence (P= 0 .00) respectively .Significant differences existed in 1/3/5-year overall survival or tumor recurrence-free survival rate post-LT among LN different expression (-,+ ,≥ + + ) in HBV-related HCC patients (P< 0 .05 ) . Multivariate analysis indicated that LN was a significantly independent predictor in predicting poor tumor recurrence-free survival post-LT (P=0 .01) .Conclusions LN may be a feasible marker in predicting HCC recurrence post-LT for HBV-related HCC patients .
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Objective To summarize the experiences of diagnosing and treating portal vein stenosis (PVS) after pediatric liver transplantation from China donation after citizen 's death (CDCD) grafts .Methods Retrospective analysis was performed for 30 cases of pediatric CDCD liver transplantation recipients with PVS .The screening ,diagnosis ,treatment and prognosis of PVS were analyzed .Results Among 218 pediatric liver transplantation recipients with CDCD grafts ,PVS was diagnosed in 30 cases with an incidence rate of 13 .8％ (30/218) .The initial diagnosis of PVS ranged from 5 days to 27 months post-operation with a median age of 2 .9 months .Ultrasonography indicated that stenotic rate of anastomotic site diameter was (41 .28 ± 12 .93)％ and blood flow velocity ratio (358 .77 ± 117 .82)％ .Intervention examination showed average pressure gradient was (9 .06 ± 5 .34) mmHg between both sides of stenosis . All cases underwent percutaneous intrahepatic balloon dilatation .The recipients were followed up for a median follow-up time of 23(3-63) months .For three cases of restenosis ,percutaneous intrahepatic balloon dilatation was repeated .Two cases underwent stent implantation due to ineffective balloon dilation .After treatment ,the stenotic rate of anastomotic site diameter was (34 .69 ± 8 .82) and blood flow velocity ratio (61 .18 ± 63 .11)％ on ultrasound while the average pressure gradient was (1 .03 ± 0 .85) mmHg .Conclusions PVS is a common vascular complication after pediatric CDCD liver transplantation .Portal vein balloon dilation is both safe and efficacious .However ,some cases require repeated balloon dilation and stent implantation serves as the last option for intractable PVS .Color ultrasound is both convenient and effective for making a primary diagnosis and evaluating outcomes .