Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is ...Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.展开更多
Liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and chronic liver disease(CLD)is limited by factors such as tumor size,number,portal venous or hepatic venous invasion and extrahepatic disease.Al...Liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and chronic liver disease(CLD)is limited by factors such as tumor size,number,portal venous or hepatic venous invasion and extrahepatic disease.Although previously established criteria,such as Milan or UCSF,have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes,there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation.Immune checkpoint inhibitors(ICI)such as atezolizumab,pembrolizumab,or nivolumab have given hope to this group of patients.We completed a comprehensive literature review using PubMed,Google Scholar,reference citation analysis,and CrossRef.The search utilized keywords such as'liver transplant','HCC','hepatocellular carcinoma','immune checkpoint inhibitors','ICI','atezolizumab',and'nivolumab'.Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT,with acceptable early outcomes comparable to other criteria.Adverse effects of ICI have also been reported during the perioperative period.In such cases,a 1.5-month interval between ICI therapy and LT has been suggested.Overall,the results of downstaging using combination immunotherapy were encouraging and promising.Early reports suggested a potential ray of hope for patients with CLD and advanced HCC,especially those with multifocal HCC or branch portal venous tumor thrombosis.However,prospective studies and further experience will reveal the optimal dosage,duration,and timing prior to LT and evaluate both short-and long-term outcomes in terms of rejection,infection,recurrence rates,and survival.展开更多
Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techni...Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management.However,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more attention.Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain normal.The approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced tolerance.The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up.No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation.With the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT recipients.Cellular strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells.The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical practice.Here,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.展开更多
BACKGROUND Liver transplantation(LT)for hepatocellular carcinoma(HCC)has been widely researched and is well established worldwide.The cornerstone of this treatment lies in the various criteria formulated by expert con...BACKGROUND Liver transplantation(LT)for hepatocellular carcinoma(HCC)has been widely researched and is well established worldwide.The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience.The variations among the criteria are staggering,and the short-and long-term outcomes are controversial.AIM To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future.METHODS We conducted a survey of major centers in India that performed LT in December 2022.A total of 23 responses were received.The centers were classified as high-and low-volume,and the current trend of care for patients undergoing LT for HCC was noted.RESULTS Of the 23 centers,35%were high volume center(>500 Liver transplants)while 52%were high-volume centers that performed more than 50 transplants/year.Approximately 39%of centers had performed>50 LT for HCC while the percent distribution for HCC in LT patients was 5%–15%in approximately 73%of the patients.Barring a few,most centers were divided equally between University of California,San Francisco(UCSF)and center-specific criteria when choosing patients with HCC for LT,and most(65%)did not have separate transplant criteria for deceased donor LT and living donor LT(LDLT).Most centers(56%)preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion.Positron-emission tomography-computed tomography(CT)was the modality of choice for metastatic workup in the majority of centers(74%).Downstaging was the preferred option for over 90%of the centers and included transarterial chemoembolization,transarterial radioembolization,stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications.The alphafetoprotein(AFP)cut-off was used by 74%of centers to decide on transplantation as well as to downstage tumors,even if they met the criteria.The criteria for successful downstaging varied,but most centers conformed to the UCSF or their center-specific criteria for LT,along with the AFP cutoff values.The wait time for LT from downstaging was at least 4–6 wk in all centers.Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52%of the centers.Approximately 65%of the centers preferred to start everolimus between 1 and 3 months post-LT.CONCLUSION The current predicted 5-year survival rate of HCC patients in India is less than 15%.The aim of transplantation is to achieve at least a 60%5-year disease free survival rate,which will provide relief to the prediction of an HCC surge over the next 20 years.The current worldwide criteria(Milan/UCSF)may have a higher 5-year survival(>70%);however,the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment,with much lower survival rates.To make predictions for 2040,we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome.With more advanced technology and better donor outcomes,LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive malignant neoplasm that requires liver transplantation(LT).Despite patients with HCC being prioritized by most organ allocation systems worldwide,they still hav...BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive malignant neoplasm that requires liver transplantation(LT).Despite patients with HCC being prioritized by most organ allocation systems worldwide,they still have to wait for long periods.Locoregional therapies(LRTs)are employed as bridging therapies in patients with HCC awaiting LT.Although largely used in the past,transarterial embolization(TAE)has been replaced by transarterial chemoembolization(TACE).However,the superiority of TACE over TAE has not been consistently shown in the literature.AIM To compare the outcomes of TACE and TAE in patients with HCC awaiting LT.METHODS All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included.All patients underwent LRT with either TACE or TAE.Some patients also underwent percutaneous ethanol injection(PEI),concom-itantly or in different treatment sessions.The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus.The primary outcome was waitlist dropout due to tumor progression,and the secondary outcome was the occurrence of adverse events.In the subset of patients who underwent LT,complete pathological response and post-transplant recurrence-free survival were also assessed.RESULTS Twelve(18.5%)patients in the TACE group(only TACE and TACE+PEI;n=65)and 3(7.9%)patients in the TAE group(only TAE and TAE+PEI;n=38)dropped out of the waitlist due to tumor progression(P log-rank test=0.29).Adverse events occurred in 8(12.3%)and 2(5.3%)patients in the TACE and TAE groups,respectively(P=0.316).Forty-eight(73.8%)of the 65 patients in the TACE group and 29(76.3%)of the 38 patients in the TAE group underwent LT(P=0.818).Among these patients,complete pathological response was detected in 7(14.6%)and 9(31%)patients in the TACE and TAE groups,respectively(P=0.145).Post-LT,HCC recurred in 9(18.8%)and 4(13.8%)patients in the TACE and TAE groups,respectively(P=0.756).Posttransplant recurrence-free survival was similar between the groups(P log-rank test=0.71).CONCLUSION Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC.Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.展开更多
The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or earl...The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.展开更多
Liver transplantation is an effective treatment for patients with end-stage liver disease. Accurate imaging evaluation of the transplanted patient is critical for ensuring that the limited donor liver is functioning a...Liver transplantation is an effective treatment for patients with end-stage liver disease. Accurate imaging evaluation of the transplanted patient is critical for ensuring that the limited donor liver is functioning appropriately. Ultrasound contrast agents(UCAs), in combination with contrastspecific imaging techniques, are increasingly accepted in clinical use for the assessment of the hepatic vasculature, bile ducts and liver parenchyma in pre-, intra- and posttransplant patients. We describe UCAs, their technical requirements, the recommended clinical indications, image interpretation and the limitations for contrastenhanced ultrasound applications in liver transplantation.展开更多
Background:Post-liver transplantation(LT)hepatocellular carcinoma(HCC)recurrence still occurs in approximately 20%of patients and drastically affects their survival.This study aimed to evaluate the efficacy of various...Background:Post-liver transplantation(LT)hepatocellular carcinoma(HCC)recurrence still occurs in approximately 20%of patients and drastically affects their survival.This study aimed to evaluate the efficacy of various treatments for recurrent HCC after LT in a Chinese population.Methods:A total of 64 HCC patients with tumor recurrence after LT were enrolled in this study.Univariate and multivariate analyses were performed to identify factors affecting post-recurrence survival.Results:Of the 64 patients with recurrent HCC after LT,those who received radical resection followed by nonsurgical therapy had a median overall survival(OS)of 20.9 months after HCC recurrence,significantly superior to patients who received only nonsurgical therapy(9.4 months)or best supportive care(2.4 months).The one-and two-year OS following recurrence was favorable for patients receiving radical resection followed by nonsurgical therapy(93.8%,52.6%),poor for patients receiving only nonsurgical therapy(30.8%,10.8%),and dismal for patients receiving best supportive care(0%,0%;overall P<0.001).Median OS in sorafenib-tolerant patients treated with lenvatinib was 19.5 months,far surpassing the patients that discontinued sorafenib or were treated with regorafenib after sorafenib failure(12 months,P<0.001).Compared with tacrolimus-based immunosuppressive therapy,OS was significantly increased with sirolimus-based therapy at one and two years after HCC recurrence(P=0.035).Multivariate analysis showed radical resection combined with nonsurgical therapy for recurrent HCC and sorafenib-lenvatinib sequential therapy were independent favorable factors for post-recurrence survival.Conclusions:Aggressive surgical intervention in well-selected patients significantly improves OS after recurrence.A multidisciplinary treatment approach is required to slow down disease progression for patients with unresectable recurrent HCC.展开更多
Background: The University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are the two most frequently used liver graft preservation fluids. The present study aimed to compare their efficacy i...Background: The University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are the two most frequently used liver graft preservation fluids. The present study aimed to compare their efficacy in end-stage hepatic alveolar echinococcosis patients who underwent ex-situ liver resection and autotransplantation (ELRA). Methods: A total of 81 patients received ELRA from August 2010 to March 2018. They were allocated into UW ( n = 48) and HTK groups ( n = 33) based on the type of solutions used. Demographic and operational data were retrospectively analyzed. Primary outcomes included 90-day mortality, incidence of early graft loss, primary dysfunction, and postoperative complications. Results: Demographic and operational characteristics were similarly distributed in the two groups. No statistically significant differences were observed with regard to 90-day mortality (12.77% vs. 12.12%) and early graft loss rate (8.51% vs. 9.09%) between the two groups. Patients in the UW and HTK groups showed a primary dysfunction rate of 27.66% and 27.27%, respectively. The UW group exhibited a higher incidence tendency of biliary complications, albeit with no statistical significance. Conclusions: This is the largest cohort study comparing the efficacy of the UW and HTK organ-preserving solutions in end-stage hepatic alveolar echinococcosis patients in ELRA settings. UW and HTK solutions presented similar efficacy and safety. A randomized clinical trial with larger scale is needed for further investigation in future clinical applications.展开更多
AIM： To study the association between host immunity and hepatitis B virus （HBV） recurrence after liver transplantation. METHODS： Peripheral blood mononuclear cells （PBMC） were isolated from 40 patients with hepa...AIM： To study the association between host immunity and hepatitis B virus （HBV） recurrence after liver transplantation. METHODS： Peripheral blood mononuclear cells （PBMC） were isolated from 40 patients with hepatitis B and underwent orthotopic liver transplantation （OLT） before and 2, 4, 8 wk after surgery. After being cultured in vitro for 72 h, the levels of INF-γ and TNF-α in culture supematants were detected with ELISA. At the same time, the quantities of HBV DNA in serum and PBMCs were measured by real time PCR. RESULTS： The levels of INF-γ and TNF-α in PBMC culture supernatants decreased before and 2, 4 wk after surgery in turns （INF-γ 155.52±72.32 ng/L vs 14.76±9.88 ng/L vs 13.22±10.35 ng/L, F= 6.946, P= 0.027〈0.05; TNF-α 80.839±46.75 ng/L vs18.59±17.29 ng/L vs9.758±7.96 ng/L, F= 22.61, P = 0.0001〈0.05）. The levels of INF-γ and TNF-α were higher in groups with phytohemagglutinin （PHA） than in those without PHA before surgery. However, the difference disappeared following OLT. Furthermore, INF-γ and TNF-α could not be detected in most patients at wk 4 and none at wk 8 after OLT. The HBV detection rate and virus load in PBMC before and 2, 4 wk after surgery were fluctuated （HBV detected rate： 51.4%, 13.3%, 50% respectively; HBV DNA： 3.55±0.674 log（10） copies/mL vs 3.00±0.329 log（10） copies/mL vs 4.608±1.344 log（10） copies/mL, F= 7.582, P= 0.002〈0.05）. HBV DNA in serum was 4.48±1.463 log（10） copies/mL before surgery and 〈 10^3 copies/mL after OLT except for one with 5.72×10^6 copies/mL 4 wk after OLT who was diagnosed as HBV recurrence. The levels of INF-γ and TNF-α were lower in patients with a high HBV load than in those with a low HBV load （HBV DNA detected/undetected in PBMCs： IFN-γ 138.08±72.44 ng/L vs 164.24±72.07 ng/L, t = 1.065, P= 0.297〉0.05, TNF-α 80.75±47.30 ng/L vs 74.10±49.70 ng/L, t= 0.407, P= 0.686〉 0.05; HBV DNA positive/negative： IFN-γ 136.77±70.04 ng/L vs 175.27±71.50 ng/L, t= 1.702, P= 0.097〉0.05; TNF-α 75.37±43.02 ng/L vs 81.53±52.46 ng/L, t = 0.402, P = 0.690〉0.05）. CONCLUSION： The yielding of INF-γ and TNF-α from PBMCs is inhibited significantly by immunosuppressive agents following OLT with HBV load increased, indicating that the impaired immunity of host is associated with HBV recurrence after OLT.展开更多
BACKGROUND Pediatric living donor liver transplantation(LDLT) has become the gold standard for patients with end-stage liver disease. With improvements in organ preservation, immunosuppression, and surgical and anesth...BACKGROUND Pediatric living donor liver transplantation(LDLT) has become the gold standard for patients with end-stage liver disease. With improvements in organ preservation, immunosuppression, and surgical and anesthesia techniques, the survival rates and long-term outcomes of patients after LDLT have significantly improved worldwide. However, data on anesthetic management and postoperative survival rate of pediatric LDLT in China are rare.AIM To review the status of pediatric LDLT in Shanghai and investigate the factors related to anesthetic management and survival rate in pediatric LDLT.METHODS We conducted a retrospective observational study to investigate the status of pediatric LDLT in Shanghai by reviewing 544 records of patients who underwent pediatric LDLT since the first operation on October 21, 2006 until August 10, 2016 at Renji Hospital and Huashan Hospital.RESULTS The 30-d, 90-d, 1-year, and 2-year survival rates were 95.22%, 93.38%, 91.36%,and 89.34%, respectively. The 2-year patient survival rate after January 1, 2011 significantly improved compared with the previous period(74.47% vs 90.74%;hazard ratio: 2.92;95% confidence interval(CI): 2.16–14.14;P = 0.0004). Median duration of mechanical ventilation in the intensive care unit(ICU) was 18 h [interquartile range(IQR), 15.25–20.25], median ICU length of stay was 6 d(IQR:4.80–9.00), and median postoperative length of stay was 24 d(IQR: 18.00–34.00).Forty-seven(8.60%) of 544 patients did not receive red blood cell transfusion during the operation.CONCLUSION Pediatric end-stage liver disease score, anesthesia duration, operation duration,intraoperative blood loss, and ICU length of stay were independent predictive factors of in-hospital patient survival. Pediatric end-stage liver disease score,operation duration, and ICU length of stay were independent predictive factors of 1-year and 3-year patient survival.展开更多
Liver transplantation for autoimmune hepatitis(AIH) is usually successful with excellent long-term outcomes,but primary disease may recur. The recurrence of AIH is a significant cause of graft loss. This study was to ...Liver transplantation for autoimmune hepatitis(AIH) is usually successful with excellent long-term outcomes,but primary disease may recur. The recurrence of AIH is a significant cause of graft loss. This study was to analyze the effect of splenectomy in preventing AIH relapse. The clinical courses of 12 patients who had transplantation for AIH were analyzed retrospectively. All patients were subjected to transplantation for end-stage liver disease caused by chronic AIH. Based on the duration of immunosuppressive treatment before liver transplantation, simultaneous splenectomy was performed in ten patients. Two patients underwent liver transplantation without splenectomy, one of them developed recurrent AIH and died from graft failure caused by AIH relapse. However, no episode of AIH recurrence was observed in patients who had undergone simultaneous splenectomy.Splenectomy might be an option to prevent AIH relapse in some patients with high risk factors.展开更多
BACKGROUND:Many studies have confirmed that serum total cholesterol(sTC) concentrations were associated with underlying liver damage and the synthesis capacity of liver.However, the role of postoperative sTC level on ...BACKGROUND:Many studies have confirmed that serum total cholesterol(sTC) concentrations were associated with underlying liver damage and the synthesis capacity of liver.However, the role of postoperative sTC level on evaluating graft function and predicting survival of recipients who underwent liver transplantation has not been discussed.METHODS:Clinical data of 231 living donor liver transplantation recipients from May 2003 to January 2015 were retrospectively collected. Patients were stratified into the low sTC group(sTC <1.42 mmol/L, 57 recipients) and high sTC group(sTC ≥1.42 mmol/L, 174 recipients) according the sTC level on postoperative day 3 based on receiver-operating characteristic curve analysis. The clinical characteristics and postoperative short-and long-term outcomes were compared between the two groups.RESULTS:Recipients with sTC <1.42 mmol/L experienced more severe preoperative disease conditions, a higher incidence of postoperative early allograft dysfunction(38.6% vs 10.3%, P<0.001), 90-day mortality(28.1% vs 10.9%, P=0.002)and severe complications(29.8% vs 17.2%, P=0.041) compared to recipients with sTC ≥1.42 mmol/L. The multivariate analysis demonstrated that sT C <1.42 mmol/L had a 4.08-fold(95% CI:1.83-9.11, P=0.001) and 2.72-fold(95% CI:1.23-6.00,P=0.013) greater risk of developing allograft dysfunction and 90-day mortality, and patients with sTC <1.42 mmol/L had poorer overall recipient and graft survival rates at 1-, 3-, and 5-year than those with sTC ≥1.42 mmol/L(67%, 61% and 61% vs 83%, 71% and 69%, P=0.025; 65%, 59% and 59% vs 81%,68% and 66%, P=0.026, respectively). Cox multivariate anal-ysis showed that sTC <1.42 mmol/L was an independent predicting factor for total recipient survival(HR=2.043; 95% CI:1.173-3.560; P=0.012) and graft survival(HR=1.905; 95% CI:1.115-3.255; P=0.018).CONCLUSIONS:sTC <1.42 mmol/L on postoperative day 3 was an independent risk factor of postoperative early allograft dysfunction, 90-day mortality, recipient and graft survival, which can be used as a marker for predicting postoperative short-and long-term outcomes.展开更多
Hepatic arterial reconstruction remains a critically challenging technique in liver transplantation,as efficient graft and patient survival are dependent on strong and continuous arterial blood supply to the donor liv...Hepatic arterial reconstruction remains a critically challenging technique in liver transplantation,as efficient graft and patient survival are dependent on strong and continuous arterial blood supply to the donor liver[1,2].Complex arterial reconstruction has been identified as a crucial risk factor for arterial thrombosis[1–5].Consequently,selecting the appropriate arterial reconstruction method to decrease hepatic artery thrombosis has garnered the attention of the surgical community.展开更多
BACKGROUND Once daily tacrolimus regimen was found to exhibits similar bioavailability,safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients.AIM To compare the efficacy a...BACKGROUND Once daily tacrolimus regimen was found to exhibits similar bioavailability,safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients.AIM To compare the efficacy and safety of once-daily prolonged release tacrolimus compared to twice-daily tacrolimus in liver transplantation patients.METHODS MEDLINE,EMBASE,CENTRAL databases were searched for clinical trials until December 2020.Efficacy outcome measured as the rate of treatment failure indicated by biopsy-proven acute rejection,Serum creatinine,graft loss,or death.Two reviewers independently selected studies,collected data and assessed risk of bias.The results are reported as risk ratio with 95%confidence interval(CI)for dichotomous data.RESULTS Seven studies included with 965 patients.All the included studies were of moderate quality according to the risk of bias assessment using Cochrane Risk of Bias tool.Biopsy-proven acute rejection was reported in four studies,and pooled analysis of those studies indicated similar rejections in both twice daily and once daily tacrolimus groups(risk ratio:1.06,95%CI:0.84-1.34,n=758,I2=0%)and also we found no significant difference between both groups for renal outcome(serum creatinine;mean difference,0.001 mg/dL,95%CI:-0.042 to 0.043,n=846,I2=18.6%).Similarly,there was similar number of adverse events such as hypertension,headache,back pain,blood related disorders,infections and nausea observed in both groups.CONCLUSION The analysis findings confirm that both once daily and twice daily tacrolimus formulations are comparable in terms of efficacy and safety outcomes.展开更多
BACKGROUND Patients with end-stage liver disease usually have varying degrees of malnutrition,and severe malnutrition may affect the prognosis of patients after liver transplantation(LT).However,there is no recommende...BACKGROUND Patients with end-stage liver disease usually have varying degrees of malnutrition,and severe malnutrition may affect the prognosis of patients after liver transplantation(LT).However,there is no recommended standard for the nutrition assessment of patients waiting for LT,and it is unknown whether malnutrition has an impact on the occurrence of postoperative complications.AIM The study aim was to investigate the value of the controlling nutritional status(CONUT)score and psoas muscle thickness per height(PMTH)in predicting prognosis in LT.METHODS We retrospectively analyzed the clinical data of 313 patients who underwent classic orthotopic LT from January 2016 to December 2018 in Tianjin First Central Hospital affiliated with Tianjin Medical University.The CONUT score is derived from the preoperative serum albumin and total cholesterol levels,and total lymphocyte count.Patients were divided into low(≤4),medium(5–8),and high(9–12)CONUT score groups perioperative characteristics,Clavien-Dindo grade III/IV/V postoperative complications,graft loss and infection,and cumulative postoperative survival in the three groups were compared 3 mo after LT.PMTH was calculated as the ratio of the transverse thickness of the psoas muscle in the umbilical plane to the height of the patient.The cutoff values of receiver operating characteristic curves were determined separately for men and women.The values were 14.1 cm/m2 for women and 17.9 cm/m2 for men.The patients were then divided into low and high PMTH groups by the cutoff values.The comparison of data between the two groups was the same as above.RESULTS Patients with medium and high CONUT scores had lower preoperative serum hemoglobin,more intraoperative red blood cell(RBC)transfusions,longer postoperative intensive care unit stay and hospital stays,higher 7 and 14 preoperative-day serum bilirubin levels,and a higher incidence of postoperative grade III/IV complications and infections than patients with low CONUT scores.Differences in the 3-mo cumulative survival among the three groups were not significant.Patients with a low PMTH had higher preoperative serum urea nitrogen,more intraoperative packed RBC and frozen plasma transfusions,longer times to postoperative ventilator extubation,higher incidence of total postoperative complications,and a lower 3-mo cumulative survival than those with a high PMTH.CONCLUSION A CONUT score≥5 and a low PMTH were both associated with poor prognosis in LT.The CONUT score had no predictive value for short-term patient survival after LT,but the PMTH was predictive of short-term patient survival after LT.展开更多
A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial con...A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.展开更多
Hepatic venous stenosis may be a cause of graft failure in living donor liver transplantation （LDLT）. Balloon dilation and metallic frame approaches have been used successfully to treat hepatic venous stenosis. Here...Hepatic venous stenosis may be a cause of graft failure in living donor liver transplantation （LDLT）. Balloon dilation and metallic frame approaches have been used successfully to treat hepatic venous stenosis. Here, we report the effect of transfemoral venous balloon dilation for treating a child with hepatic venous stenosis after LDLT .展开更多
BACKGROUND Hydatid cyst disease(HCD)is common in certain locations.Surgery is associated with postoperative biliary fistula(POBF)and recurrence.The primary aim of this study was to identify whether occult cysto-biliar...BACKGROUND Hydatid cyst disease(HCD)is common in certain locations.Surgery is associated with postoperative biliary fistula(POBF)and recurrence.The primary aim of this study was to identify whether occult cysto-biliary communication(CBC)can predict recurrent HCD.The secondary aim was to assess the role of cystic fluid bilirubin and alkaline phosphatase(ALP)levels in predicting POBF and recurrent HCD.AIM To identify whether occult CBC can predict recurrent HCD.The secondary aim was to assess the role of cystic fluid bilirubin and ALP levels in predicting POBF and recurrent HCD.METHODS From September 2010 to September 2016,a prospective multicenter study was undertaken involving 244 patients with solitary primary superficial stage cystic echinococcosis 2 and cystic echinococcosis 3b HCD who underwent laparoscopic partial cystectomy with omentoplasty.Univariable logistic regression analysis assessed independent factors determining biliary complications and recurrence.RESULTS There was a highly statistically significant association(P≤0.001)between cystic fluid biochemical indices and the development of biliary complications(of 16 patients with POBF,15 patients had high cyst fluid bilirubin and ALP levels),where patients with high bilirubin-ALP levels were 3405 times more likely to have biliary complications.There was a highly statistically significant association(P≤0.001)between biliary complications,biochemical indices,and the occurrence of recurrent HCD(of 30 patients with recurrent HCD,15 patients had high cyst fluid bilirubin and ALP;all 16 patients who had POBF later developed recurrent HCD),where patients who developed biliary complications and high bilirubin-ALP were 244.6 and 214 times more likely to have recurrent hydatid cysts,respectively.CONCLUSION Occult CBC can predict recurrent HCD.Elevated cyst fluid bilirubin and ALP levels predicted POBF and recurrent HCD.展开更多
BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mecha...BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear.AIM To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders.METHODS Liver samples were collected from 16 healthy donors(HDs)and 17 advanced HBV-ACLF patients who were eligible for liver transplantation.The mitochondrial ultrastructure,metabolic characteristics,and immune microenvironment of the liver were assessed.More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF.RESULTS Compared with HDs,there was extensive hepatocyte necrosis,immune cell infiltration,and ductular reaction in patients with ACLF.In patients,the liver suffered severe hypoxia,as evidenced by increased expression of hypoxia-inducible factor-1α.Swollen mitochondria and cristae were observed in the liver of patients.The number,length,width,and area of mitochondria were adaptively increased in hepatocytes.Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased,while anaerobic glycolysis was enhanced in patients with HBV-ACLF.These findings suggested that,to a greater extent,hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source.Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate,which stimulates peripheral monocyte infiltration into the liver.Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68^(+)HLA-DR^(+)macrophages and elevated levels of both interleukin-1βand transforming growth factor-β1 in their livers.The abundance of CD206^(+)CD163^(+)macrophages and expression of interleukin-10 decreased.The correlation analysis revealed that hepatic organic acid metabolites were closely associated with macrophage-derived cytokines/chemokines.CONCLUSION The results indicated that bioenergetic alteration driven by hypoxia and mitochondrial dysfunction affects hepatic immune and metabolic remodeling,leading to advanced HBV-ACLF.These findings highlight a new therapeutic target for improving the treatment of HBV-ACLF.展开更多
基金supported by funding from the National Key Research and Development Program of China(Grant No.2021 YFA1100500)The Major Research Plan of the National Natural Science Foundation of China(Grant No.92159202)+3 种基金Key Program,National Natural Science Foundation of China(Grant No.81930016)National Natural Science Foundation of China(Grant No.82300743)Zhejiang Provincial Natural Science Foundation of China(Grant No.LQ23H160044)Key Research&Development Program of Zhejiang Province(Grant Nos.2019C03050,2022C03108,and 2021C03118)。
文摘Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.
文摘Liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and chronic liver disease(CLD)is limited by factors such as tumor size,number,portal venous or hepatic venous invasion and extrahepatic disease.Although previously established criteria,such as Milan or UCSF,have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes,there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation.Immune checkpoint inhibitors(ICI)such as atezolizumab,pembrolizumab,or nivolumab have given hope to this group of patients.We completed a comprehensive literature review using PubMed,Google Scholar,reference citation analysis,and CrossRef.The search utilized keywords such as'liver transplant','HCC','hepatocellular carcinoma','immune checkpoint inhibitors','ICI','atezolizumab',and'nivolumab'.Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT,with acceptable early outcomes comparable to other criteria.Adverse effects of ICI have also been reported during the perioperative period.In such cases,a 1.5-month interval between ICI therapy and LT has been suggested.Overall,the results of downstaging using combination immunotherapy were encouraging and promising.Early reports suggested a potential ray of hope for patients with CLD and advanced HCC,especially those with multifocal HCC or branch portal venous tumor thrombosis.However,prospective studies and further experience will reveal the optimal dosage,duration,and timing prior to LT and evaluate both short-and long-term outcomes in terms of rejection,infection,recurrence rates,and survival.
基金Supported by the National Natural Science Foundation of China,No.82000586 and No.82241221and Shanghai Immune Therapy Institute.
文摘Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management.However,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more attention.Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain normal.The approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced tolerance.The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up.No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation.With the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT recipients.Cellular strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells.The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical practice.Here,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.
文摘BACKGROUND Liver transplantation(LT)for hepatocellular carcinoma(HCC)has been widely researched and is well established worldwide.The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience.The variations among the criteria are staggering,and the short-and long-term outcomes are controversial.AIM To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future.METHODS We conducted a survey of major centers in India that performed LT in December 2022.A total of 23 responses were received.The centers were classified as high-and low-volume,and the current trend of care for patients undergoing LT for HCC was noted.RESULTS Of the 23 centers,35%were high volume center(>500 Liver transplants)while 52%were high-volume centers that performed more than 50 transplants/year.Approximately 39%of centers had performed>50 LT for HCC while the percent distribution for HCC in LT patients was 5%–15%in approximately 73%of the patients.Barring a few,most centers were divided equally between University of California,San Francisco(UCSF)and center-specific criteria when choosing patients with HCC for LT,and most(65%)did not have separate transplant criteria for deceased donor LT and living donor LT(LDLT).Most centers(56%)preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion.Positron-emission tomography-computed tomography(CT)was the modality of choice for metastatic workup in the majority of centers(74%).Downstaging was the preferred option for over 90%of the centers and included transarterial chemoembolization,transarterial radioembolization,stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications.The alphafetoprotein(AFP)cut-off was used by 74%of centers to decide on transplantation as well as to downstage tumors,even if they met the criteria.The criteria for successful downstaging varied,but most centers conformed to the UCSF or their center-specific criteria for LT,along with the AFP cutoff values.The wait time for LT from downstaging was at least 4–6 wk in all centers.Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52%of the centers.Approximately 65%of the centers preferred to start everolimus between 1 and 3 months post-LT.CONCLUSION The current predicted 5-year survival rate of HCC patients in India is less than 15%.The aim of transplantation is to achieve at least a 60%5-year disease free survival rate,which will provide relief to the prediction of an HCC surge over the next 20 years.The current worldwide criteria(Milan/UCSF)may have a higher 5-year survival(>70%);however,the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment,with much lower survival rates.To make predictions for 2040,we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome.With more advanced technology and better donor outcomes,LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.
基金Supported by Financiamento e IncentivoàPesquisa(FIPE/HCPA)of Hospital de Clínicas de Porto Alegre,No.2020-0473.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive malignant neoplasm that requires liver transplantation(LT).Despite patients with HCC being prioritized by most organ allocation systems worldwide,they still have to wait for long periods.Locoregional therapies(LRTs)are employed as bridging therapies in patients with HCC awaiting LT.Although largely used in the past,transarterial embolization(TAE)has been replaced by transarterial chemoembolization(TACE).However,the superiority of TACE over TAE has not been consistently shown in the literature.AIM To compare the outcomes of TACE and TAE in patients with HCC awaiting LT.METHODS All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included.All patients underwent LRT with either TACE or TAE.Some patients also underwent percutaneous ethanol injection(PEI),concom-itantly or in different treatment sessions.The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus.The primary outcome was waitlist dropout due to tumor progression,and the secondary outcome was the occurrence of adverse events.In the subset of patients who underwent LT,complete pathological response and post-transplant recurrence-free survival were also assessed.RESULTS Twelve(18.5%)patients in the TACE group(only TACE and TACE+PEI;n=65)and 3(7.9%)patients in the TAE group(only TAE and TAE+PEI;n=38)dropped out of the waitlist due to tumor progression(P log-rank test=0.29).Adverse events occurred in 8(12.3%)and 2(5.3%)patients in the TACE and TAE groups,respectively(P=0.316).Forty-eight(73.8%)of the 65 patients in the TACE group and 29(76.3%)of the 38 patients in the TAE group underwent LT(P=0.818).Among these patients,complete pathological response was detected in 7(14.6%)and 9(31%)patients in the TACE and TAE groups,respectively(P=0.145).Post-LT,HCC recurred in 9(18.8%)and 4(13.8%)patients in the TACE and TAE groups,respectively(P=0.756).Posttransplant recurrence-free survival was similar between the groups(P log-rank test=0.71).CONCLUSION Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC.Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.
基金funding received in the form of the Catherine Marie Enright research scholarship from the Royal Australasian College of Surgeons to support his program of research
文摘The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.
基金Supported by National Natural Science Foundation of ChinaNo.81371554+1 种基金Science and Technology Planning Project of Guangdong Province of ChinaNo.2013B021800092
文摘Liver transplantation is an effective treatment for patients with end-stage liver disease. Accurate imaging evaluation of the transplanted patient is critical for ensuring that the limited donor liver is functioning appropriately. Ultrasound contrast agents(UCAs), in combination with contrastspecific imaging techniques, are increasingly accepted in clinical use for the assessment of the hepatic vasculature, bile ducts and liver parenchyma in pre-, intra- and posttransplant patients. We describe UCAs, their technical requirements, the recommended clinical indications, image interpretation and the limitations for contrastenhanced ultrasound applications in liver transplantation.
基金the grants from National S&T Major Project(2017ZX10203205)the Medical Science and Technology Project of Zhejiang Province(2014KYA082)+1 种基金the Fundamental Research Funds for the Central Universities(2018FZA7002)the Shulan Talent Foundation.
文摘Background:Post-liver transplantation(LT)hepatocellular carcinoma(HCC)recurrence still occurs in approximately 20%of patients and drastically affects their survival.This study aimed to evaluate the efficacy of various treatments for recurrent HCC after LT in a Chinese population.Methods:A total of 64 HCC patients with tumor recurrence after LT were enrolled in this study.Univariate and multivariate analyses were performed to identify factors affecting post-recurrence survival.Results:Of the 64 patients with recurrent HCC after LT,those who received radical resection followed by nonsurgical therapy had a median overall survival(OS)of 20.9 months after HCC recurrence,significantly superior to patients who received only nonsurgical therapy(9.4 months)or best supportive care(2.4 months).The one-and two-year OS following recurrence was favorable for patients receiving radical resection followed by nonsurgical therapy(93.8%,52.6%),poor for patients receiving only nonsurgical therapy(30.8%,10.8%),and dismal for patients receiving best supportive care(0%,0%;overall P<0.001).Median OS in sorafenib-tolerant patients treated with lenvatinib was 19.5 months,far surpassing the patients that discontinued sorafenib or were treated with regorafenib after sorafenib failure(12 months,P<0.001).Compared with tacrolimus-based immunosuppressive therapy,OS was significantly increased with sirolimus-based therapy at one and two years after HCC recurrence(P=0.035).Multivariate analysis showed radical resection combined with nonsurgical therapy for recurrent HCC and sorafenib-lenvatinib sequential therapy were independent favorable factors for post-recurrence survival.Conclusions:Aggressive surgical intervention in well-selected patients significantly improves OS after recurrence.A multidisciplinary treatment approach is required to slow down disease progression for patients with unresectable recurrent HCC.
基金supported by grants from Xinjiang Uyghur Autonomous Region Key Laboratory Open Research Program(No.2018D03002)the National Natural Science Foundation of China(No.81560329)+1 种基金Xinjiang Uyghur Autonomous Region Key Scientific Research Program(No.201430123–2)State Key Laboratory of Pathogenesis,Prevention,Treatment of High Incidence Diseases in Central Asia Fund(No.SKL-HIDCA-2017-Y2)
文摘Background: The University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are the two most frequently used liver graft preservation fluids. The present study aimed to compare their efficacy in end-stage hepatic alveolar echinococcosis patients who underwent ex-situ liver resection and autotransplantation (ELRA). Methods: A total of 81 patients received ELRA from August 2010 to March 2018. They were allocated into UW ( n = 48) and HTK groups ( n = 33) based on the type of solutions used. Demographic and operational data were retrospectively analyzed. Primary outcomes included 90-day mortality, incidence of early graft loss, primary dysfunction, and postoperative complications. Results: Demographic and operational characteristics were similarly distributed in the two groups. No statistically significant differences were observed with regard to 90-day mortality (12.77% vs. 12.12%) and early graft loss rate (8.51% vs. 9.09%) between the two groups. Patients in the UW and HTK groups showed a primary dysfunction rate of 27.66% and 27.27%, respectively. The UW group exhibited a higher incidence tendency of biliary complications, albeit with no statistical significance. Conclusions: This is the largest cohort study comparing the efficacy of the UW and HTK organ-preserving solutions in end-stage hepatic alveolar echinococcosis patients in ELRA settings. UW and HTK solutions presented similar efficacy and safety. A randomized clinical trial with larger scale is needed for further investigation in future clinical applications.
基金Supported by the Technology Program of Guangdong Province, No. 2004B35001001
文摘AIM： To study the association between host immunity and hepatitis B virus （HBV） recurrence after liver transplantation. METHODS： Peripheral blood mononuclear cells （PBMC） were isolated from 40 patients with hepatitis B and underwent orthotopic liver transplantation （OLT） before and 2, 4, 8 wk after surgery. After being cultured in vitro for 72 h, the levels of INF-γ and TNF-α in culture supematants were detected with ELISA. At the same time, the quantities of HBV DNA in serum and PBMCs were measured by real time PCR. RESULTS： The levels of INF-γ and TNF-α in PBMC culture supernatants decreased before and 2, 4 wk after surgery in turns （INF-γ 155.52±72.32 ng/L vs 14.76±9.88 ng/L vs 13.22±10.35 ng/L, F= 6.946, P= 0.027〈0.05; TNF-α 80.839±46.75 ng/L vs18.59±17.29 ng/L vs9.758±7.96 ng/L, F= 22.61, P = 0.0001〈0.05）. The levels of INF-γ and TNF-α were higher in groups with phytohemagglutinin （PHA） than in those without PHA before surgery. However, the difference disappeared following OLT. Furthermore, INF-γ and TNF-α could not be detected in most patients at wk 4 and none at wk 8 after OLT. The HBV detection rate and virus load in PBMC before and 2, 4 wk after surgery were fluctuated （HBV detected rate： 51.4%, 13.3%, 50% respectively; HBV DNA： 3.55±0.674 log（10） copies/mL vs 3.00±0.329 log（10） copies/mL vs 4.608±1.344 log（10） copies/mL, F= 7.582, P= 0.002〈0.05）. HBV DNA in serum was 4.48±1.463 log（10） copies/mL before surgery and 〈 10^3 copies/mL after OLT except for one with 5.72×10^6 copies/mL 4 wk after OLT who was diagnosed as HBV recurrence. The levels of INF-γ and TNF-α were lower in patients with a high HBV load than in those with a low HBV load （HBV DNA detected/undetected in PBMCs： IFN-γ 138.08±72.44 ng/L vs 164.24±72.07 ng/L, t = 1.065, P= 0.297〉0.05, TNF-α 80.75±47.30 ng/L vs 74.10±49.70 ng/L, t= 0.407, P= 0.686〉 0.05; HBV DNA positive/negative： IFN-γ 136.77±70.04 ng/L vs 175.27±71.50 ng/L, t= 1.702, P= 0.097〉0.05; TNF-α 75.37±43.02 ng/L vs 81.53±52.46 ng/L, t = 0.402, P = 0.690〉0.05）. CONCLUSION： The yielding of INF-γ and TNF-α from PBMCs is inhibited significantly by immunosuppressive agents following OLT with HBV load increased, indicating that the impaired immunity of host is associated with HBV recurrence after OLT.
基金the National Natural Science Foundation of China,No.81571030,No.81771133 and No.81970995Shanghai Pudong New Area Municipal Commission of Health and Family Planning Funding,No.PW2016D-4+1 种基金Shanghai Jiao Tong University integration funding of Medicine and Engineering,No.YG2017MS53Shanghai Shenkang Hospital Development Center Funding,No.SHDC12017X11.
文摘BACKGROUND Pediatric living donor liver transplantation(LDLT) has become the gold standard for patients with end-stage liver disease. With improvements in organ preservation, immunosuppression, and surgical and anesthesia techniques, the survival rates and long-term outcomes of patients after LDLT have significantly improved worldwide. However, data on anesthetic management and postoperative survival rate of pediatric LDLT in China are rare.AIM To review the status of pediatric LDLT in Shanghai and investigate the factors related to anesthetic management and survival rate in pediatric LDLT.METHODS We conducted a retrospective observational study to investigate the status of pediatric LDLT in Shanghai by reviewing 544 records of patients who underwent pediatric LDLT since the first operation on October 21, 2006 until August 10, 2016 at Renji Hospital and Huashan Hospital.RESULTS The 30-d, 90-d, 1-year, and 2-year survival rates were 95.22%, 93.38%, 91.36%,and 89.34%, respectively. The 2-year patient survival rate after January 1, 2011 significantly improved compared with the previous period(74.47% vs 90.74%;hazard ratio: 2.92;95% confidence interval(CI): 2.16–14.14;P = 0.0004). Median duration of mechanical ventilation in the intensive care unit(ICU) was 18 h [interquartile range(IQR), 15.25–20.25], median ICU length of stay was 6 d(IQR:4.80–9.00), and median postoperative length of stay was 24 d(IQR: 18.00–34.00).Forty-seven(8.60%) of 544 patients did not receive red blood cell transfusion during the operation.CONCLUSION Pediatric end-stage liver disease score, anesthesia duration, operation duration,intraoperative blood loss, and ICU length of stay were independent predictive factors of in-hospital patient survival. Pediatric end-stage liver disease score,operation duration, and ICU length of stay were independent predictive factors of 1-year and 3-year patient survival.
文摘Liver transplantation for autoimmune hepatitis(AIH) is usually successful with excellent long-term outcomes,but primary disease may recur. The recurrence of AIH is a significant cause of graft loss. This study was to analyze the effect of splenectomy in preventing AIH relapse. The clinical courses of 12 patients who had transplantation for AIH were analyzed retrospectively. All patients were subjected to transplantation for end-stage liver disease caused by chronic AIH. Based on the duration of immunosuppressive treatment before liver transplantation, simultaneous splenectomy was performed in ten patients. Two patients underwent liver transplantation without splenectomy, one of them developed recurrent AIH and died from graft failure caused by AIH relapse. However, no episode of AIH recurrence was observed in patients who had undergone simultaneous splenectomy.Splenectomy might be an option to prevent AIH relapse in some patients with high risk factors.
基金supported by grants from the National Science and Technology Major Project of China(2012ZX10002-016 and 2012ZX10002-017)
文摘BACKGROUND:Many studies have confirmed that serum total cholesterol(sTC) concentrations were associated with underlying liver damage and the synthesis capacity of liver.However, the role of postoperative sTC level on evaluating graft function and predicting survival of recipients who underwent liver transplantation has not been discussed.METHODS:Clinical data of 231 living donor liver transplantation recipients from May 2003 to January 2015 were retrospectively collected. Patients were stratified into the low sTC group(sTC <1.42 mmol/L, 57 recipients) and high sTC group(sTC ≥1.42 mmol/L, 174 recipients) according the sTC level on postoperative day 3 based on receiver-operating characteristic curve analysis. The clinical characteristics and postoperative short-and long-term outcomes were compared between the two groups.RESULTS:Recipients with sTC <1.42 mmol/L experienced more severe preoperative disease conditions, a higher incidence of postoperative early allograft dysfunction(38.6% vs 10.3%, P<0.001), 90-day mortality(28.1% vs 10.9%, P=0.002)and severe complications(29.8% vs 17.2%, P=0.041) compared to recipients with sTC ≥1.42 mmol/L. The multivariate analysis demonstrated that sT C <1.42 mmol/L had a 4.08-fold(95% CI:1.83-9.11, P=0.001) and 2.72-fold(95% CI:1.23-6.00,P=0.013) greater risk of developing allograft dysfunction and 90-day mortality, and patients with sTC <1.42 mmol/L had poorer overall recipient and graft survival rates at 1-, 3-, and 5-year than those with sTC ≥1.42 mmol/L(67%, 61% and 61% vs 83%, 71% and 69%, P=0.025; 65%, 59% and 59% vs 81%,68% and 66%, P=0.026, respectively). Cox multivariate anal-ysis showed that sTC <1.42 mmol/L was an independent predicting factor for total recipient survival(HR=2.043; 95% CI:1.173-3.560; P=0.012) and graft survival(HR=1.905; 95% CI:1.115-3.255; P=0.018).CONCLUSIONS:sTC <1.42 mmol/L on postoperative day 3 was an independent risk factor of postoperative early allograft dysfunction, 90-day mortality, recipient and graft survival, which can be used as a marker for predicting postoperative short-and long-term outcomes.
基金the Fundamental Research Funds for the Central Universities(2022ZFJH003)the Major Research Plan of the National Natural Science Foundation of China(92159202)+1 种基金the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2022016B)Zhejiang Provincial Natural Science Foundation of China g(Y21H160259).
文摘Hepatic arterial reconstruction remains a critically challenging technique in liver transplantation,as efficient graft and patient survival are dependent on strong and continuous arterial blood supply to the donor liver[1,2].Complex arterial reconstruction has been identified as a crucial risk factor for arterial thrombosis[1–5].Consequently,selecting the appropriate arterial reconstruction method to decrease hepatic artery thrombosis has garnered the attention of the surgical community.
文摘BACKGROUND Once daily tacrolimus regimen was found to exhibits similar bioavailability,safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients.AIM To compare the efficacy and safety of once-daily prolonged release tacrolimus compared to twice-daily tacrolimus in liver transplantation patients.METHODS MEDLINE,EMBASE,CENTRAL databases were searched for clinical trials until December 2020.Efficacy outcome measured as the rate of treatment failure indicated by biopsy-proven acute rejection,Serum creatinine,graft loss,or death.Two reviewers independently selected studies,collected data and assessed risk of bias.The results are reported as risk ratio with 95%confidence interval(CI)for dichotomous data.RESULTS Seven studies included with 965 patients.All the included studies were of moderate quality according to the risk of bias assessment using Cochrane Risk of Bias tool.Biopsy-proven acute rejection was reported in four studies,and pooled analysis of those studies indicated similar rejections in both twice daily and once daily tacrolimus groups(risk ratio:1.06,95%CI:0.84-1.34,n=758,I2=0%)and also we found no significant difference between both groups for renal outcome(serum creatinine;mean difference,0.001 mg/dL,95%CI:-0.042 to 0.043,n=846,I2=18.6%).Similarly,there was similar number of adverse events such as hypertension,headache,back pain,blood related disorders,infections and nausea observed in both groups.CONCLUSION The analysis findings confirm that both once daily and twice daily tacrolimus formulations are comparable in terms of efficacy and safety outcomes.
基金Nation Natural Science Foundation of China(General Program),No.81870444Natural Science Foundation of Tianjin,No.17JCQNJC12800.
文摘BACKGROUND Patients with end-stage liver disease usually have varying degrees of malnutrition,and severe malnutrition may affect the prognosis of patients after liver transplantation(LT).However,there is no recommended standard for the nutrition assessment of patients waiting for LT,and it is unknown whether malnutrition has an impact on the occurrence of postoperative complications.AIM The study aim was to investigate the value of the controlling nutritional status(CONUT)score and psoas muscle thickness per height(PMTH)in predicting prognosis in LT.METHODS We retrospectively analyzed the clinical data of 313 patients who underwent classic orthotopic LT from January 2016 to December 2018 in Tianjin First Central Hospital affiliated with Tianjin Medical University.The CONUT score is derived from the preoperative serum albumin and total cholesterol levels,and total lymphocyte count.Patients were divided into low(≤4),medium(5–8),and high(9–12)CONUT score groups perioperative characteristics,Clavien-Dindo grade III/IV/V postoperative complications,graft loss and infection,and cumulative postoperative survival in the three groups were compared 3 mo after LT.PMTH was calculated as the ratio of the transverse thickness of the psoas muscle in the umbilical plane to the height of the patient.The cutoff values of receiver operating characteristic curves were determined separately for men and women.The values were 14.1 cm/m2 for women and 17.9 cm/m2 for men.The patients were then divided into low and high PMTH groups by the cutoff values.The comparison of data between the two groups was the same as above.RESULTS Patients with medium and high CONUT scores had lower preoperative serum hemoglobin,more intraoperative red blood cell(RBC)transfusions,longer postoperative intensive care unit stay and hospital stays,higher 7 and 14 preoperative-day serum bilirubin levels,and a higher incidence of postoperative grade III/IV complications and infections than patients with low CONUT scores.Differences in the 3-mo cumulative survival among the three groups were not significant.Patients with a low PMTH had higher preoperative serum urea nitrogen,more intraoperative packed RBC and frozen plasma transfusions,longer times to postoperative ventilator extubation,higher incidence of total postoperative complications,and a lower 3-mo cumulative survival than those with a high PMTH.CONCLUSION A CONUT score≥5 and a low PMTH were both associated with poor prognosis in LT.The CONUT score had no predictive value for short-term patient survival after LT,but the PMTH was predictive of short-term patient survival after LT.
文摘A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.
基金supported by a grant from Jiangsu Health Department of China (RC2007058)
文摘Hepatic venous stenosis may be a cause of graft failure in living donor liver transplantation （LDLT）. Balloon dilation and metallic frame approaches have been used successfully to treat hepatic venous stenosis. Here, we report the effect of transfemoral venous balloon dilation for treating a child with hepatic venous stenosis after LDLT .
文摘BACKGROUND Hydatid cyst disease(HCD)is common in certain locations.Surgery is associated with postoperative biliary fistula(POBF)and recurrence.The primary aim of this study was to identify whether occult cysto-biliary communication(CBC)can predict recurrent HCD.The secondary aim was to assess the role of cystic fluid bilirubin and alkaline phosphatase(ALP)levels in predicting POBF and recurrent HCD.AIM To identify whether occult CBC can predict recurrent HCD.The secondary aim was to assess the role of cystic fluid bilirubin and ALP levels in predicting POBF and recurrent HCD.METHODS From September 2010 to September 2016,a prospective multicenter study was undertaken involving 244 patients with solitary primary superficial stage cystic echinococcosis 2 and cystic echinococcosis 3b HCD who underwent laparoscopic partial cystectomy with omentoplasty.Univariable logistic regression analysis assessed independent factors determining biliary complications and recurrence.RESULTS There was a highly statistically significant association(P≤0.001)between cystic fluid biochemical indices and the development of biliary complications(of 16 patients with POBF,15 patients had high cyst fluid bilirubin and ALP levels),where patients with high bilirubin-ALP levels were 3405 times more likely to have biliary complications.There was a highly statistically significant association(P≤0.001)between biliary complications,biochemical indices,and the occurrence of recurrent HCD(of 30 patients with recurrent HCD,15 patients had high cyst fluid bilirubin and ALP;all 16 patients who had POBF later developed recurrent HCD),where patients who developed biliary complications and high bilirubin-ALP were 244.6 and 214 times more likely to have recurrent hydatid cysts,respectively.CONCLUSION Occult CBC can predict recurrent HCD.Elevated cyst fluid bilirubin and ALP levels predicted POBF and recurrent HCD.
基金the Domestic First-class Construction Disciplines of the Hunan University of Chinese MedicinePostgraduate Research Innovation Program of Hunan Province,No.CX20220771Clinical MedTech Innovation Project of Hunan Province,No.2021SK51415.
文摘BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear.AIM To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders.METHODS Liver samples were collected from 16 healthy donors(HDs)and 17 advanced HBV-ACLF patients who were eligible for liver transplantation.The mitochondrial ultrastructure,metabolic characteristics,and immune microenvironment of the liver were assessed.More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF.RESULTS Compared with HDs,there was extensive hepatocyte necrosis,immune cell infiltration,and ductular reaction in patients with ACLF.In patients,the liver suffered severe hypoxia,as evidenced by increased expression of hypoxia-inducible factor-1α.Swollen mitochondria and cristae were observed in the liver of patients.The number,length,width,and area of mitochondria were adaptively increased in hepatocytes.Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased,while anaerobic glycolysis was enhanced in patients with HBV-ACLF.These findings suggested that,to a greater extent,hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source.Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate,which stimulates peripheral monocyte infiltration into the liver.Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68^(+)HLA-DR^(+)macrophages and elevated levels of both interleukin-1βand transforming growth factor-β1 in their livers.The abundance of CD206^(+)CD163^(+)macrophages and expression of interleukin-10 decreased.The correlation analysis revealed that hepatic organic acid metabolites were closely associated with macrophage-derived cytokines/chemokines.CONCLUSION The results indicated that bioenergetic alteration driven by hypoxia and mitochondrial dysfunction affects hepatic immune and metabolic remodeling,leading to advanced HBV-ACLF.These findings highlight a new therapeutic target for improving the treatment of HBV-ACLF.
