Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients

BACKGROUND Mesenchymal stem cells(MSCs)as living biopharmaceuticals with unique properties,i.e.,stemness,viability,phenotypes,paracrine activity,etc.,need to be administered such that they reach the target site,maintaining these properties unchanged and are retained at the injury site to participate in the repair process.Route of delivery(RoD)remains one of the critical determinants of safety and efficacy.This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure(HF)based on phase II randomized clinical trials(RCTs).We hypothesize that the RoD modulates the safety and efficacy of MSCbased therapy and determines the outcome of the intervention.AIM To investigate the effect of RoD of MSCs on safety and efficacy in HF patients.METHODS RCTs were retrieved from six databases.Safety endpoints included mortality and serious adverse events(SAEs),while efficacy outcomes encompassed changes in left ventricular ejection fraction(LVEF),6-minute walk distance(6MWD),and pro-B-type natriuretic peptide(pro-BNP).Subgroup analyses on RoD were performed for all study endpoints.RESULTS Twelve RCTs were included.Overall,MSC therapy demonstrated a significant decrease in mortality[relative risk(RR):0.55,95%confidence interval(95%CI):0.33-0.92,P=0.02]compared to control,while SAE outcomes showed no significant difference(RR:0.84,95%CI:0.66-1.05,P=0.11).RoD subgroup analysis revealed a significant difference in SAE among the transendocardial(TESI)injection subgroup(RR=0.71,95%CI:0.54-0.95,P=0.04).The pooled weighted mean difference(WMD)demonstrated an overall significant improvement of LVEF by 2.44%(WMD:2.44%,95%CI:0.80-4.29,P value≤0.001),with only intracoronary(IC)subgroup showing significant improvement(WMD:7.26%,95%CI:5.61-8.92,P≤0.001).Furthermore,the IC delivery route significantly improved 6MWD by 115 m(WMD=114.99 m,95%CI:91.48-138.50),respectively.In biochemical efficacy outcomes,only the IC subgroup showed a significant reduction in pro-BNP by-860.64 pg/mL(WMD:-860.64 pg/Ml,95%CI:-944.02 to-777.26,P=0.001).CONCLUSION Our study concluded that all delivery methods of MSC-based therapy are safe.Despite the overall benefits in efficacy,the TESI and IC routes provided better outcomes than other methods.Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.

Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus

BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.

越南非洲猪瘟疫苗AVAC ASF LIVE(ASFV-G-ΔMGF)研究工作分析与思考

非洲猪瘟(Afcrian swine fever,ASF)是由非洲猪瘟病毒(African swine fever virus,ASFV)感染引起的烈性传染病。近日,越南正式将经临床试验验证的非洲猪瘟弱毒疫苗AVAC ASF LIVE(ASFV-G-ΔMGF)在其全国推广使用。本文对越南非洲猪瘟弱毒疫苗ASFV-G-ΔMGF相关研究数据进行了总结分析,分别从ASFVG-ΔMGF株攻毒保护能力评价、传代细胞培养株临床动物实验、野猪口服接种试验、毒力返强验证等方面,结合国内相关ASFV基因缺失株试验数据进行了分析。总结分析发现:越南上市的ASFV-G-ΔMGF疫苗株,二次免疫接种后攻毒保护效果更好,但在对野猪的口服接种评价中,其口鼻接种效果存在不确定性;随着疫苗株在动物体内的不断传代,其存在毒力返强和毒株变异风险,导致接种猪只临床症状明显;ASFV-G-ΔMGF株虽然有较好的攻毒保护能力和可靠的生产优势,但仍缺乏相关研究数据,特别是在垂直传播、交叉保护、基因突变等方面。后续仍需对ASFV-G-ΔMGF株的临床应用效果进一步评价。

Living-donor vs deceased-donor liver transplantation for patients with hepatocellular carcinoma

With the increasing prevalence of living-donor liver transplantation(LDLT) for patients with hepatocellular carcinoma(HCC),some authors have reported a potential increase in the HCC recurrence rates among LDLT recipients compared to deceased-donor liver transplantation(DDLT) recipients.The aim of this review is to encompass current opinions and clinical reports regarding differences in the outcome,especially the recurrence of HCC,between LDLT and DDLT.While some studies report impaired recurrence- free survival and increased recurrence rates among LDLT recipients,others,including large database studies,report comparable recurrence- free survival and recurrence rates between LDLT and DDLT.Studies supporting the increased recurrence in LDLT have linked graft regeneration to tumor progression,but we found no association between graft regeneration/initial graft volume and tumor recurrence among our 125 consecutive LDLTs for HCC cases.In the absence of a prospective study regarding the use of LDLT vs DDLT for HCC patients,there is no evidence to support the higher HCC recurrence after LDLT than DDLT,and LDLT remains a reasonable treatment option for HCC patients with cirrhosis.

法舒地尔缓解β-淀粉样蛋白1-42诱导的SH-SY5Y细胞凋亡

背景:法舒地尔对阿尔茨海默病小鼠脑内的线粒体动力学有调节作用,并且可以抑制神经炎症,但能否调节线粒体自噬和NLRP3炎症小体进而减轻β-淀粉样蛋白毒性尚不清楚。目的:探究法舒地尔对β-淀粉样蛋白1-42诱导的人源神经母细胞瘤细胞株SH-SY5Y凋亡和线粒体自噬以及NLRP3炎症小体的调节作用。方法:将SH-SY5Y细胞接种于孔板内,细胞贴壁后分3组干预:对照组不加入任何药物,模型组加入20μmol/L β-淀粉样蛋白1-42,法舒地尔组同时加入20μmol/L β-淀粉样蛋白1-42与15 mg/L法舒地尔,干预24 h后,采用MTT法检测细胞活性,TUNEL染色检测细胞凋亡,qRT-PCR和Western blot检测凋亡相关蛋白表达,免疫荧光染色和Western blot检测线粒体自噬相关蛋白表达,免疫荧光染色和Western blot检测NLRP3炎症小体相关蛋白表达。结果与结论:(1)与对照组比较,模型组细胞活性降低、凋亡率升高(P<0.05);与模型组比较,法舒地尔组细胞活性升高、凋亡率降低(P<0.05);(2)qRT-PCR和Western blot检测结果显示,与对照组比较,模型组细胞Bax mRNA与蛋白表达升高(P<0.05),Bcl-2 mRNA与蛋白表达降低(P<0.05);与模型组比较,法舒地尔组细胞Bax mRNA与蛋白表达降低(P<0.05),Bcl-2 mRNA与蛋白表达升高(P<0.05);(3)免疫荧光染色和Western blot检测结果显示,与对照组相比,模型组细胞PINK1、帕金森病蛋白和LC3蛋白表达降低(P<0.05),p62蛋白表达升高(P<0.05);与模型组相比,法舒地尔组细胞PINK1、帕金森病蛋白和LC3蛋白表达升高(P<0.05),p62蛋白表达降低(P<0.05);(4)免疫荧光染色和Western blot检测结果显示,与对照组相比,模型组细胞NLRP3、ASC、Caspase-1和白细胞介素1β蛋白表达升高(P<0.05);与模型组相比,法舒地尔组细胞NLRP3、ASC、Caspase-1和白细胞介素1β蛋白表达降低(P<0.05);(5)结果表明,法舒地尔可以减轻β-淀粉样蛋白1-42诱导的SH-SY5Y细胞凋亡,其机制可能与激活线粒体自噬且抑制NLRP3炎症小体激活有关。

Doppler ultrasonography in living donor liver transplantation recipients: Intra- and post-operative vascular complications

Living-donor liver transplantation has provided a solution to the severe lack of cadaver grafts for the replacement of liver afflicted with end-stage cirrhosis, fulminant disease, or inborn errors of metabolism. Vascular complications remain the most serious complications and a common cause for graft failure after hepatic transplantation. Doppler ultrasound remains the primary radiological imaging modality for the diagnosis of such complications. This article presents a brief review of intra- and post-operative living donor liver transplantation anatomy and a synopsis of the role of ultrasonography and color Doppler in evaluating the graft vascular haemodynamics both during surgery and post-operatively in accurately defining the early vascular complications. Intra-operative ultrasonography of the liver graft provides the surgeon with useful real-time diagnostic and staging information that may result in an alteration in the planned surgical approach and corrections of surgical complications during the procedure of vascular anastomoses. The relevant intraoperative anatomy and the spectrum of normal and abnormal findings are described. Ultrasonography and color Doppler also provides the clinicians and surgeons early post-operative potential developmental complications that may occur during hospital stay. Early detection and thus early problem solving can make the difference between graft survival and failure.

A comparison of desensitization methods: Rituximab with/without plasmapheresis in ABO-incompatible living donor liver transplantation

Background: Plasmapheresis is a desensitization method used prior to ABO-incompatible(ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking.Methods: Fifty-six adult patients underwent ABO-I living donor liver transplantation between January2012 and October 2015. A single dose of rituximab(300 mg/m~2) was administered 2 weeks before surgery with plasmapheresis in all patients until February 2014(RP group, n = 26). Patients were administered rituximab only, without plasmapheresis between March 2014 and October 2015(RO group, n = 30).Results: The 6-, 12-and 18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and 96.6%, 85.4% and 85.4% in the RO group, respectively(P = 0.574). When the initial isoagglutinin titers < 16, neither group showed a rebound rise of isoagglutinin titers. For patients with initial isoagglutinin titers ≥ 16, the rebound rise of isoagglutinin titers was more prominent in the RP group. There was no difference in time-dependent changes in B cell subpopulations and ABO-I-related complications.Conclusions: Sufficient desensitization for ABO-I living donor liver transplantation can be achieved using rituximab alone. This desensitization strategy does not affect the isoagglutinin titers, ABO-I-related complications and patient survival.

The pre-Kasai procedure in living donor liver transplantation for children with biliary atresia

BACKGROUND:Biliary atresia(BA) is a major cause of chronic cholestasis,a fatal disorder in infants.This study was undertaken to evaluate the safety and effectiveness of primary living donor liver transplantation(LDLT) in comparison with the traditional first-line treatment,the Kasai procedure.METHODS:We assessed 28 children with BA at age of less than two years(3-21.3 months) who had undergone LDLT in two hospitals in Southwest China during the period of 2008-2011.Eighteen children who had had primary LDLT were included in a primary LDLT group,and ten children who had undergone the Kasai operation in a pre-Kasai group.All patients were followed up after discharge from the hospital.The records of the BA patients and donors were reviewed.RESULTS:The time of follow-up ranged 12-44.5 months with a median of 31 months.The 30-day and 1-year survival rates were 85.7% and 78.6%,respectively.There was no significant difference in the 30-day or 1-year survival between the two groups(83.3% vs 90% and 77.8% vs 80%,P】0.05).The main cause of death was hepatic artery thrombosis.There were more patients with complications who required intensive medical care or re-operation in the pre-Kasai group(8,80%) than in the primary LDLT group(9,50%)(P=0.226).But no significant differences were observed in operating time(9.3 vs 8.9 hours,P=0.77),intraoperative blood loss(208.6 vs 197.0 mL,P=0.84) and blood transfusion(105.6 vs 100.0 mL,P=0.91) between the two groups.The durations of ICU and hospital stay in the primary LDLT group and pre-Kasai group were 180.4 vs 157.7 hours(P=0.18) and 27 vs 29 days(P=0.29),respectively.CONCLUSIONS:Primary LDLT is a safe and efficient management for young pediatric patients with BA.Compared with the outcome of LDLT for patients receiving a previous Kasai operation,a similar survival rate and a low rate of re-operation and intensive medical care for patients with BA can be obtained.

Clinical analysis of patients with hepatocellular carcinoma recurrence after living-donor liver transplantation

AIM: To evaluated patterns and outcomes of hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT).METHODS: From 2001 to 2014, 293 patients underwent LDLT for HCC at our transplant center. We retrospectively reviewed 54 (18.4%) patients with HCC recurrence after LDLT. We evaluated patterns and outcomes of HCC recurrence after LDLT, with particular attention to the Milan criteria at transplantation, treatments for HCC-recurrent patients, and factors related to survival after HCC recurrence. Furthermore, we evaluated the efficacy of combination treatment of sorafenib and an mTOR inhibitor.RESULTS: The 1-, 2-, and 3-year overall survival rates after HCC recurrence were 41.1%, 20.5%, and 15.4%, respectively. The median time interval between LDLT and HCC recurrence was 6.5 mo. Although recurrence rates according to the Milan criteria at LDLT were significantly different, HCC recurrence patterns and survival rates after HCC recurrence were not significantly different between the two groups. Time to recurrence &#x0003c; 12 mo (P = 0.048), multiple recurrences at HCC recurrence (P = 0.038), and palliative treatment for recurrent tumors (P = 0.003) were significant independent prognostic factors for poor survival after HCC recurrence in a multivariate analysis. The combination treatment of sorafenib and sirolimus showed survival benefits in the palliative treatment group (P = 0.005).CONCLUSION: Curative treatment for recurrent HCC after LDLT is the most important factor in survival rates after HCC recurrence and combination treatments of sorafenib and an mTOR inhibitor could have survival benefits in patients with HCC recurrence after LT in the palliative treatment group.

Efficacy of middle hepatic vein reconstruction in adult right-lobe living donor liver transplantation

BACKGROUND: Congestion of the right anterior segment may lead to graft dysfunction in right-lobe living donor liver transplantation (LDLT) without a middle hepatic vein (MHV) trunk. Selective reconstruction of MHV tributaries with the interposition of vascular grafts has been introduced to overcome this problem. However, there is still no consensus on the definite criteria of MHV reconstruction. METHODS: LDLT patients were reviewed to evaluate the effects of MHV reconstruction. From March 2005 to September 2008 in our transplantation center, 120 consecutive LDLTs were performed using a right-lobe graft without a MHV. Excluding 11 patients, among the remainder, 73 (67%) had reconstructed MHV tributaries, and the others 36 (33%) did not. The values of liver functional index and liver graft regeneration ratio were compared between the two groups. RESULTS: There was a prolonged period of liver functional recovery in patients with small-for-size grafts and a graft-recipient weight ratio (GRWR) <1.0%, and without MHV reconstruction. The ratio of liver regeneration 1 month postoperatively in reconstruction cases was 81%, versus 78% in patients without reconstruction (P=0.352), but among small-for-size grafts, there was a significant difference between the two groups (95% vs. 80%). CONCLUSION: Our study shows that reconstruction of MHV tributaries is not necessary in all patients, but is beneficial for patients with GRWR <1.0%. (Hepatobiliary Pancrent Dis Int 2010; 9: 135-138)

Conversion of twice-daily to once-daily tacrolimus is safe in stable adult living donor liver transplant recipients

Once-daily extended-release tacrolimus （Tac-OD） has been introduced as a useful therapeutic option to increase patient adherence to immunosuppressive therapy. This study aimed to evaluate the safety, efficacy and immunosuppressant adherence of conversion from twice-daily tacrolimus （Tac-BID） to Tac-OD in stable adult living donor liver transplant （LDLT） recipients in a single institution. METHODS： Between February and May 2013, Tac-BID was converted to Tac-OD in recipients followed up for at least 12 months after transplantation and without previous rejection episodes. The switching policy was based on a dose ratio of 1：1 with dose adjustment target trough levels at 3-5 ng/mL. Tacro- limus trough levels, laboratory parameters, metabolic disor- ders, and adverse events were assessed. RESULTS： A total of 229 patients were enrolled in the study. The median age at conversion was 53 years （range 31-73）. The median transplant duration was 35.3 months （range 12.0-95.4）. During a median follow-up of 13.5 months after conversion, 9 patients returned to Tac-BID because of adverse events. No acute rejection episodes were observed. Of 214 patients still on Tac-OD at 12 months, 12 （5.6%） received a reduced dose and 95 （44.4%） required an increased dose over baseline. Overall adherence was 82.2% at the end of follow-up. CONCLUSION： The conversion from Tac-BID to Tac-OD with similar target trough levels after conversion is safe and effec- tive for long-term stable LDLT patients.

Analysis of CD8^+CD28^-T-suppressor cells in living donor liver transplant recipients

BACKGROUND:Human CD8 + CD28 - T-suppressor(Ts) cells have been considered to indicate a reduced need for immunosuppression in pediatric liver-intestine transplant recipients and recipients of deceased heart-kidney transplants.However,in adult-to-adult living donor liver transplantation(A-A LDLT)little information is available and the clinical significance is still unknown. METHODS:Flow cytometry was used to detect the population of CD8+CD28 -Ts cells present in peripheral blood in A-A LDLT recipients(n=31),patients with end- stage liver disease(n=24)and healthy controls(n=19). Meanwhile,we tested the graft function and trough levels of immunosuppression in recipients.The clinical and follow- up data of 31 transplant recipients were analyzed. RESULTS:Compared with diseased controls(P=0.007) and healthy individuals(P=0.000),a notable expansion of CD8 + CD28 - Ts cells was found in recipients of A-A LDLT.This was associated with graft function,levels of immunosuppression and rejection episodes. CONCLUSIONS:To monitor the CD8 + CD28 - Ts cells levels is important to evaluate the immune state of recipients. Meanwhile,it is also important to promote expansion of CD8+CD28 -Ts cells in recipients of A-A LDLT,not only to sustain good graft function and decrease the dosage of immunosuppressants,but also to reduce the occurrence of rejection.

Graft-to-recipient weight ratio lower to 0.7% is safe without portal pressure modulation in right-lobe living donor liver transplantation with favorable conditions

BACKGROUND: The low graft-to-recipient weight ratio(GRWR) in adult-to-adult living donor liver transplantation(LDLT) is one of the major risk factors affecting graft survival. The goal of this study was to evaluate whether the lower limit of the GRWR can be safely reduced without portal pressure modulation in right-lobe LDLT. METHODS: From 2005 to 2011, 317 consecutive patients from a single institute underwent LDLT with right-lobe grafts without portal pressure modulation. Of these, 23 had a GRWR of less than 0.7%(group A), 27 had a GRWR of ≥0.7%, 【0.8%(group B), and 267 had a GRWR of more than and equal to 0.8%(group C). Medical records, including recipient, donor, operation factors, laboratory findings and complications were reviewed retrospectively. RESULTS: The baseline demographics showed low model for end-stage liver disease score(mean 16.3±8.9) and high percentage of hepatocellular carcinoma(231 patients, 72.9%). Three groups by GRWR demonstrated similar characteristics except recipient body mass index and donor gender. For smallforsize syndrome, there were 3(13.0%) in group A, 1(3.7%) in group B, and 2 patients(0.7%) in group C(P【0.001). Hepatic artery thrombosis was more frequently observed in group A than in groups B and C(8.7% vs 3.7% vs 1.9%, P=0.047). However, among the three groups, graft survival rates at 1 year(100% vs 96.3% vs 93.6%) and 3 years(91.7% vs 73.2% vs 88.1%) were not different(P=0.539). In laboratory measurements,there was no group difference in total bilirubin and albumin. However, prothrombin time was longer in group A within postoperative 1 week and platelet count was lower in groups A and B within postoperative 1 month. CONCLUSION: A GRWR lower to 0.7% is safe and does not need to modulate portal pressure in adult-to-adult LDLT using the right-lobe in favorable conditions including low model for end-stage liver disease score.

Small-for-size syndrome in living donor liver transplantation

When the graft volume is too small to satisfy the recipient’s metabolic demand, the recipient may thus experience small-for-size syndrome (SFSS). Because the occurrence of SFSS is determined by not only the liver graft volume but also a combination of multiple negative factors, the definitions of small-for-size graft (SFSG) and SFSS are different in each institute and at each time. In the clinical setting, surgical inflow modulation and maximizing the graft outflow are keys to overcoming SFSS. Accordingly, relatively smaller-sized grafts can be used with surgical modification and pharmacological manipulation targeting portal circulation and liver graft quality. Therefore, the focus of the SFSG issue is now shifting from how to obtain a larger graft from the living donor to how to manage the use of a smaller graft to save the recipient, considering donor safety to be a priority.

Outcome of patients undergoing right lobe living donor liver transplantation with small-for-size grafts

AIM: To investigate the outcome of living donor liver transplantation (LDLT) recipients transplanted with small-for-size grafts (SFSGs). METHODS: Between November 2001 and December 2010, 196 patients underwent LDLT with right lobe liver grafts at our center. Recipients were divided into 2 treatment groups: group A with an actuarial graft-to-recipient weight ratio (aGRWR) < 0.8% (n = 45) and group B with an aGRWR = 0.8% (n = 151). We evaluated serum liver function markers within 4 wk after transplantation. We also retrospectively evaluated the outcomes of these patients for potential effects related to the recipients, the donors and the transplantation procedures based upon a review of their medical records. RESULTS: Small-for-size syndrome (SFSS) developed in 7 of 45 patients (15.56%) in group A and 9 of 151 patients (5.96%) in group B (P = 0.080). The levels of alanine aminotransferase and aspartate aminotransferase in group A were higher than those in group B during early period after transplantation, albeit not sig-nificantly. The cumulative 1-, 3-and 5-year liver graft survival rates were 82.22%, 71.11% and 71.11% for group A and 81.46%, 76.82%, and 75.50% for group B patients, respectively (P = 0.623). However, univariate analysis of risk factors associated with graft survival in group A demonstrated that the occurrence of SFSS after LDLT was the only significant risk factor affecting graft survival (P < 0.001). Furthermore, multivariate analysis of our data did not identify any additional significant risk factors accounting for poor graft survival. CONCLUSION: Our study suggests that LDLT recipients with an aGRWR < 0.8% may have liver graft outcomes comparable to those who received larger size grafts. Further studies are required to ascertain the safety of using SFSGs. (c) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Survival outcomes of right-lobe living donor liver transplantation for patients with high Model for End-stage Liver Disease scores

BACKGROUND: Controversy exists over whether living donor liver transplantation (LDLT) should be offered to patients with high Model for End-stage Liver Disease (MELD) scores. This study tried to determine whether a high MELD score would result in inferior outcomes of right-lobe LDLT. METHODS: Among 411 consecutive patients who received right-lobe LDLT at our center, 143 were included in this study. The patients were divided into two groups according to their MELD scores: a high-score group (MELD score ≥25; n=75) and a low-score group (MELD score 【25; n=68). Their demographic data and perioperative conditions were compared. Univariable and multivariable analyses were performed to identify risk factors affecting patient survival. RESULTS: In the high-score group, more patients required preoperative intensive care unit admission (49.3% vs 2.9%; P【0.001), mechanical ventilation (21.3% vs 0%; P【0.001), or hemodialysis (13.3% vs 0%; P=0.005); the waiting time before LDLT was shorter (4 vs 66 days; P【0.001); more blood was transfused during operation (7 vs 2 units; P【0.001); patients stayed longer in the intensive care unit (6 vs 3 days; P【0.001) and hospital (21 vs 15 days; P=0.015) after transplantation;more patients developed early postoperative complications (69.3% vs 50.0%; P=0.018); and values of postoperative peak blood parameters were higher. However, the two groups had comparable hospital mortality. Graft survival and patient overall survival at one year (94.7% vs 95.6%; 95.9% vs 96.9%), three years (91.9% vs 92.6%; 93.2% vs 95.3%), and five years (90.2% vs 90.2%; 93.2% vs 95.3%) were also similar between the groups. CONCLUSIONS: Although the high-score group had signifi-cantly more early postoperative complications, the two groups had comparable hospital mortality and similar satisfactory rates of graft survival and patient overall survival. Therefore, a high MELD score should not be a contraindication to right-lobe LDLT if donor risk and recipient benefit are taken into full account.

Impact of small-for-size liver grafts on medium-term and long-term graft survival in living donor liver transplantation: A meta-analysis

BACKGROUND Small-for-size grafts (SFSGs) in living donor liver transplantation (LDLT) could optimize donor postoperative outcomes and also expand the potential donor pool. Evidence on whether SFSGs would affect medium-term and long-term recipient graft survival is lacking. AIM To evaluate the impact of small-for-size liver grafts on medium-term and longterm graft survival in adult to adult LDLT. METHODS A systematic review and meta-analysis were performed by searching eligible studies published before January 24, 2019 on PubMed, EMBASE, and Web of Science databases. The primary outcomes were 3-year and 5-year graft survival. Incidence of small-for-size syndrome and short term mortality were also extracted. RESULTS This meta-analysis is reported according to the guidelines of the PRISMA 2009 Statement. Seven retrospective observational studies with a total of 1821 LDLT recipients were included in the meta-analysis. SFSG is associated with significantly poorer medium-term graft survival. The pooled odds ratio for 3-year graft survival was 1.58 [95% confidence interval 1.10-2.29, P = 0.014]. On the other hand, pooled results of the studies showed that SFSG had no significant discriminatory effect on 5-year graft survival with an odds ratio of 1.31 (95% confidence interval 0.87-1.97, P = 0.199). Furthermore, incidence of small-for-size syndrome detected in recipients of SFSG ranged from 0-11.4% in the included studies. CONCLUSION SFSG is associated with inferior medium-term but not long-term graft survival. Comparable long-term graft survival based on liver graft size shows that smaller grafts could be accepted for LDLT with appropriate flow modulatory measures. Close follow-up for graft function is warranted within 3 years after liver transplantation.

Proposal of new expanded selection criteria using total tumor size and ^(18)F-fluorodeoxyglucose- positron emission tomography/computed tomography for living donor liver transplantation in patients with hepatocellular carcinoma:The National Cancer Center K

AIM: To expand the living donor liver transplantation(LT) pool of eligible patients with hepatocellular carcinoma(HCC) using new morphological and biological criteria.METHODS: Patients with HCC who underwent living donor LT(LDLT) from March 2005 to May 2013 at the National Cancer Center Korea(NCCK) were enrolled. We performed the 18F-fluorodeoxyglucose positron emission tomography/computed tomography(PET/CT)before LDLT. Overall and disease-free survival analysis was done in patients to evaluate the usefulness of new NCCK criteria using PET/CT and total tumor size(10 cm).RESULTS: We enrolled a total of 280 patients who pathologically confirmed to have HCC and performed the PET/CT before transplantation. Among them, 164(58.6%) patients fulfilled the NCCK criteria and 132 patients(47.1%) met the Milan criteria. Five-year overall and disease-free survival rates for patients who fulfilled the NCCK criteria showed 85.2% and 84.0%, respectively, and were significantly higher than those beyond the NCCK criteria(60.2% and 44.4%, respectively; P < 0.001). The correlation analysis between preoperative imaging tests and pathologic reports using Cohen's Kappa demonstrated the better results in the NCCK criteria than those in the Milan criteria(0.850 vs 0.583). The comparison of diseasefree analysis among the NCCK, Milan, and University of California, San Francisco(UCSF) criteria using the receiver operating characteristics curves revealed the similar area under the curve value criteria(NCCK vs Milan, P = 0.484; NCCK vs UCSF, P = 0.189 at 5-years).CONCLUSION: The NCCK criteria using hybrid concept of both morphological and biological parameters showed an excellent agreement between preoperative imaging and pathological results, and favorable survival outcomes. These new criteria might select the optimal patients with HCC waiting LDLT and expand the selection pool.

Living donor liver transplantation in 43 children with biliary atresia: a single-center experience from the mainland of China

BACKGROUND: There is no large-cohort report on living donor liver transplantation (LDLT) for biliary atresia (BA) patients from the mainland of China. This single-center study describes our initial experience with 43 LDLTs for BA patients aged two years or younger. METHODS: In this study, the eligibility criteria were BA as the primary diagnosis and two years of age or younger. From October 2006 to December 2010, the clinical data of 43 LDLTs, including pre-operative evaluations, surgical techniques, postoperative complications and outcomes of donors and recipients, were retrospectively analyzed. RESULTS: Donor graft type was the left lateral segment with compatible ABO blood groups. Forty-three recipients were selected in this study. The median patient age at operation was 9 months (range 6-24), and the median body weight was 8 kg (range 5.7-12.5). Fourteen (32.6%) recipients received Kasai operations before liver transplantation. The overall one- and two-year cumulative survival rates for grafts and recipients were 81%, 81% and 76%, 76%, respectively. No donor mortality was encountered, with a minimal morbidity and no long- term sequelae. Nine out of 43 recipients died. Postoperative complications of recipients were biliary leakage and refluxing cholangitis (11/43, 25.6%), hepatic artery thrombosis (4, 9.3%), pulmonary infections (4, 9.3%), portal vein thrombosis (3, 7.0%), wound disruption (3, 7.0%), acute rejection (3, 7.0%), cytomegalovirus infection (2, 4.7%), and intra-abdominal bleeding (1, 2.3%).CONCLUSION: Despite the relatively low survival rates due to lack of experience initially, LDLT still provides encouraging outcomes for pediatric recipients with BA, even small children under two years old.

Modified techniques for adult-to-adult living donor liver transplantation

BACKGROUND: Because of critical organ shortage, transplant professionals have utilized living donor liver transplantation (LDLT) in recent years. We summarized our experience in adult-to-adult LDLT with grafts of right liver lobe by a modified technique. METHODS: From January 2002 to August 2005, 24 adult patients underwent living donor liver transplantation with grafts of the right liver lobe at West China Hospital, Sichuan University, China. Twenty-two patients underwent modi-Bed procedures designed to improve the reconstruction of the right hepatic vein and the tributaries of the middle hepatic vein by interposing a great saphenous vein ( GSV) graft and the anastomosis of the hepatic arteries and bile ducts. RESULTS: No severe complications and death occurred in all donors. In the first 2 patients, (patients 1 and 2), operative procedure was not modified. One patient suffered from 'small-for-size syndrome' and the other died of sepsis with progressive deterioration of graft function. In the rest 22 patients (patients 3 to 24), however, the procedure of venous reconstruction was modified, and better results were obtained. Complications occurred in 7 recipients including acute rejection (2 patients), hepatic artery thrombosis (1), bile leakage (1), intestinal bleeding (1), left sub-phrenic abscess (1), and pulmonary infection (1). One patient with pulmonary infection died of multiple organ failure (MOF). The 22 patients underwent direct anastomosis of the right hepatic vein to the inferior vena cava (IVC), 9 direct anastomosis plus the reconstruction of the right inferior hepatic vein, and 10 direct anastomosis plus the reconstruction of the tributaries of the middle hepatic vein by in-terpos-ing a GSV graft to provide sufficient venous outflow. Trifurcation of the portal vein was met in 3 patients. Venoplasty or separate anastomosis was performed. The ratio of graft to recipient body weight ranged from 0.72% to 1.17%. Among these patients, 19 had the ratio <1.0% and 4 <0.8%, and the ratio of graft weight to recipient standard liver volume was between 31.86% and 62.48%. Among these patients, 10 had the ratio <50% and 2 <40%. No 'small-for-size syndrome' occurred in the 22 recipients who were subjected to modified procedures. CONCLUSIONS: With the modified surgical techniques for the reconstruction of the hepatic vein to obtain an adequate outflow and provide a sufficient functioning liver mass, living donor liver graft in adults using the right lobe can be safe to prevent the 'small-for-size syndrome'.