Predicting major adverse cardiovascular events after orthotopic liver transplantation using a supervised machine learning model:A cohort study

BACKGROUND Liver transplant(LT)patients have become older and sicker.The rate of post-LT major adverse cardiovascular events(MACE)has increased,and this in turn raises 30-d post-LT mortality.Noninvasive cardiac stress testing loses accuracy when applied to pre-LT cirrhotic patients.AIM To assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional cohort.METHODS This retrospective cohort study involved 575 LT patients from a Southern Brazilian academic center.We developed a predictive model for post-LT MACE(defined as a composite outcome of stroke,new-onset heart failure,severe arrhythmia,and myocardial infarction)using the extreme gradient boosting(XGBoost)machine learning model.We addressed missing data(below 20%)for relevant variables using the k-nearest neighbor imputation method,calculating the mean from the ten nearest neighbors for each case.The modeling dataset included 83 features,encompassing patient and laboratory data,cirrhosis complications,and pre-LT cardiac assessments.Model performance was assessed using the area under the receiver operating characteristic curve(AUROC).We also employed Shapley additive explanations(SHAP)to interpret feature impacts.The dataset was split into training(75%)and testing(25%)sets.Calibration was evaluated using the Brier score.We followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for reporting.Scikit-learn and SHAP in Python 3 were used for all analyses.The supplementary material includes code for model development and a user-friendly online MACE prediction calculator.RESULTS Of the 537 included patients,23(4.46%)developed in-hospital MACE,with a mean age at transplantation of 52.9 years.The majority,66.1%,were male.The XGBoost model achieved an impressive AUROC of 0.89 during the training stage.This model exhibited accuracy,precision,recall,and F1-score values of 0.84,0.85,0.80,and 0.79,respectively.Calibration,as assessed by the Brier score,indicated excellent model calibration with a score of 0.07.Furthermore,SHAP values highlighted the significance of certain variables in predicting postoperative MACE,with negative noninvasive cardiac stress testing,use of nonselective beta-blockers,direct bilirubin levels,blood type O,and dynamic alterations on myocardial perfusion scintigraphy being the most influential factors at the cohort-wide level.These results highlight the predictive capability of our XGBoost model in assessing the risk of post-LT MACE,making it a valuable tool for clinical practice.CONCLUSION Our study successfully assessed the feasibility and accuracy of the XGBoost machine learning model in predicting post-LT MACE,using both cardiovascular and hepatic variables.The model demonstrated impressive performance,aligning with literature findings,and exhibited excellent calibration.Notably,our cautious approach to prevent overfitting and data leakage suggests the stability of results when applied to prospective data,reinforcing the model’s value as a reliable tool for predicting post-LT MACE in clinical practice.

Hepatofugal Portal Flow Associated with Acute Rejection in Living-donor Auxiliary Partial Orthotopic Liver Transplantation:A Report of One Case and Literature Review

We report a case of reversible hepatofugal portal flow after auxiliary partial orthotopic liver transplantation (APOLT) from a living donor in this study.On postoperative day 6,continuous hepatofugal portal flow was observed in the grafted liver without portal thrombosis and obstruction of the hepatic vein.Based on histological findings,acute rejection was the suspected cause.The normal portal venous flow was restored after steroid pulse and antithymocyte globulin (ATG) therapies.The patient was discharged on the 30th postoperative day.It was concluded that hepatofugal flow after liver transplantation is a sign of serious acute rejection,and can be successfully treated by anti-rejection therapy.

Establishment of a new pig model for auxiliary partial orthotopic liver transplantation

AIM: To establish a new pig model for auxiliary partial orthotopic liver transplantation (APOLT).METHODS: The liver of the donor was removed from its body. The left lobe of the liver was resected in vivo and the right lobe was used as a graft. After the left lateral lobe of the recipient was resected, end-to-side anastomoses of suprahepatic inferior vena cava and portal vein were performed between the donor and recipient livers,respectively. End-to-end anastomoses were made between hepatic artery of graft and splenic artery of the host.Outside drainage was placed in donor common bile duct.RESULTS: Models of APOLT were established in 5 pigs with a success rate of 80%. Color ultrasound examination showed an increase of blood flow of graft on 5th d compared to the first day after operation. When animals were killed on the 5th d after operation, thrombosis of hepatic vein (HV) and portal vein (PV) were not found. Histopathological examination of liver samples revealed evidence of damage with mild steatosis and sporadic necrotic hepatocytes and focal hepatic lobules structure disorganized in graft. Infiltration of inflammatory cells was mild in portal or central vein area. Hematologic laboratory values and blood chemical findings revealed that compared with group A (before transplantation), mean arterial pressure (MAP), central venous pressure (CVP), buffer base (BB), standard bicarbonate (SB) and K+ in group B (after portal vein was clamped) decreased (P＜0.01). After reperfusion of the graft, MAP, CVP and K+ restored gradually.CONCLUSION: Significant decrease of congestion in portal vein and shortened blocking time were obtained because of the application of in vitro veno-venous bypass during complete vascular clamping. This new procedure,with such advantages as simple vessel processing, quality anastomosis, less postoperative hemorrhage and higher success rate, effectively prevents ischemia reperfusion injury of the host liver and deserves to be spread.

Novel alternative transplantation therapy for orthotopic liver transplantation in liver failure:A systematic review

BACKGROUND Orthotopic liver transplantation(OLT)is the only treatment for end-stage liver failure;however,graft shortage impedes its applicability.Therefore,studies investigating alternative therapies are plenty.Nevertheless,no study has comprehensively analyzed these therapies from different perspectives.AIM To summarize the current status of alternative transplantation therapies for OLT and to support future research.METHODS A systematic literature search was performed using PubMed,Cochrane Library and EMBASE for articles published between January 2010 and 2018,using the following MeSH terms:[(liver transplantation)AND cell]OR[(liver transplantation)AND differentiation]OR[(liver transplantation)AND organoid]OR[(liver transplantation)AND xenotransplantation].Various types of studies describing therapies to replace OLT were retrieved for full-text evaluation.Among them,we selected articles including in vivo transplantation.RESULTS A total of 89 studies were selected.There are three principle forms of treatment for liver failure:Xeno-organ transplantation,scaffold-based transplantation,and cell transplantation.Xeno-organ transplantation was covered in 14 articles,scaffold-based transplantation was discussed in 22 articles,and cell transplantation was discussed in 53 articles.Various types of alternative therapies were discussed:Organ liver,25 articles;adult hepatocytes,31 articles;fetal hepatocytes,three articles;mesenchymal stem cells(MSCs),25 articles;embryonic stem cells,one article;and induced pluripotent stem cells,three articles and other sources.Clinical applications were discussed in 12 studies:Cell transplantation using hepatocytes in four studies,five studies using umbilical cord-derived MSCs,three studies using bone marrow-derived MSCs,and two studies using hematopoietic stem cells.CONCLUSION The clinical applications are present only for cell transplantation.Scaffold-based transplantation is a comprehensive treatment combining organ and cell transplantations,which warrants future research to find relevant clinical applications.

Details determining the success in establishing a mouse orthotopic liver transplantation model

Liver transplantation(LT)is currently the only effective treatment option for endstage liver disease.The importance of animal models in transplantation is widely recognized among researchers.Because of the well-characterized mouse genome and the greater diversity and availability of both genetically modified animals and research reagents,mouse orthotopic LT(MOLT)has become an ideal model for the investigation of liver biology,tissue injury,regulation of alloimmunity and tolerance induction,and the pathogenesis of specific liver diseases.However,due to its complicated and technically demanding procedure,the model has merely been used by only a few research groups in the world for years.For a new learner,training lasting at least a couple of months or even years is required.Most of the investigators have emphasized the importance of elaborate techniques and dedicated instruments in establishing a MOLT model,but some details are often neglected.The nontechnical details are also significant,especially for researchers who have little experience in mouse microsurgery.Here,we review and summarize the crucial technical and nontechnical details in establishing the model of MOLT based on scientific articles and our experience in six aspects:animal selection,anesthesia,perioperative management,organ procurement,back-table preparation,and implantation surgery.We aim to enable research groups to shorten the learning curve and implement the mouse LT procedure with high technical success.

Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice

AIM: To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice.METHODS: BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors, and were implanted into the liver to establish orthotopic transplantation tumor models of human hepatocellular carcinoma in nude mice. Seventy-five animals were randomized divided into five groups (n = 15). Bufalin was injected intraperitoneally into three groups at doses of 1.5 mg/kg (BF1), 1 mg/kg (BF2) and 0.5 mg/kg (BF3) for d 15-24, respectively. The NS group was injected an equal volume of saline as above and adriamycin was injected intraperitoneally into the ADM group at a dose of 8.0 mg/kg for d 15. Ten mice in each group were killed at d 25 and the survival time in each group was calculated. We also observed the morphologic alterations in the myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscopy, measured the apoptotic rate by TUNEL staining method, and detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and RT-PCR in tumor tissues. RESULTS: The tumor volumes in each group of bufalin were reduced significantly (35.21 ± 12.51 vs 170.39 ± 25.29; 49.83 ± 11.46 vs 170.39 ± 25.29; 83.99 ± 24.63 vs 170.39 ± 25.29, P < 0.01, respectively), and the survival times were prolonged in group BF1-2 (31.8 ± 4.2 vs 23.4 ± 2.1 and 29.4 ± 3.4 vs 23.4 ± 2.1, P < 0.05, respectively), and necrosis was mainly in severe or moderate degree in group BF1-2. No morphologicalchanges were detected in the myocardium, brain, liver and kidney tissues. Apoptotic characteristics could be seen in group BF1-2. The positive rates of bcl-2 and bax protein expression of each group by immunohistochemical staining were 10.0%, 10.0%, 20.0%, 10.0% and 20.0%; 90.0%, 80.0%, 80.0%, 40.0% and 30.0%, respectively. Loss of expression of bcl-2 mRNA in each group was to be found and the density of bax mRNA was increased progressively with increase of dose of bufalin by RT-PCR. CONCLUSION: Bufalin has significant anti-tumor activities in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice with no marked toxicity and was able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax, which may be involved in its anti-tumor mechanism of bufalin.

Percutaneous interventional therapy for anastomotic biliary strictures after orthotopic liver transplantation

Objective To describe the technique,efficacy, and safety of percutaneous interventional therapy for anastomotic biliary strictures after orthotopic liver transplantation ( OLT) . Methods From May 2004 to December 2009,25 patients with anastomotic biliary stric-

Multi-factor analysis of initial poor graft function after orthotopic liver transplantation

BACKGROUND: In the early period of orthotopic liver transplantation (OLT), initial poor graft function (IPGF) is one of the complications which leads to primary graft non-function (PGNF) in serious cases. This study set out to establish the clinical risk factors resulting in IPGF after OLT. METHODS: Eighty cases of OLT were analyzed. The IPGF group consisted of patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) above 1500 IU/L within 72 hours after OLT, while those in the non-IPGF group had values below 1500 IU/L. Recipient-associated factors before OLT analyzed were age, sex, primary liver disease and Child-Pugh classification; factors analyzed within the peri-operative period were non-heart beating time (NHBT), cold ischemia time (CIT), rewarming ischemic time (RWIT), liver biopsy at the end of cold ischemia; and factors analyzed within 72 hours after OLT were ALT and/or AST values. A logistic regression model was applied to filter the possible factors resulting in IPGF. RESULTS: Donor NHBT, CIT and RWIT were significantly longer in the IPGF group than in the non-IPGF group; in the logistic regression model, NHBT was the risk factor leading to IPGF (P < 0.05), while CIT and RWIT were possible risk factors. In one case in the IPGF group, PGNF appeared with moderate hepatic steatosis. CONCLUSIONS: Longer NHBT is an important risk factor leading to IPGF, while serious steatosis in the donor liver, CIT and RWIT are potential risk factors.

Management of biliary complications after orthotopic liver transplantation:The role of endoscopy

Biliary complications are signifi cant causes of morbidity and mortality after orthotopic liver transplantation (OLT). The estimated incidence of biliary complications after OLT ranges between 10%-25%,however,these numbers continue to decline due to improvement in surgical techniques. The most common biliary complications are strictures (both anastomotic and non-anastomotic) and bile leaks. Most of these problems can be appropriately managed with endoscopic retrograde colangiography (ERC). Other complications such as bile duct stones,bile casts,sphincter of Oddi dysfunction,and hemobilia,are less frequent and also can be managed with ERC. This article will review the risk factors,diagnosis,and endoscopic management of the most common biliary complications after OLT.

Impact of hypoxic preconditioning on apoptosis and its possible mechanism in orthotopic liver autotransplantation in rats

BACKGROUND: Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is considered to have protective effects on HIRI. This study was designed to explore the impact of HP on apoptosis and its possible mechanism during orthotopic liver autotransplantation. METHODS: A modified orthotopic liver autotransplantation model was used to simulate HIRI. Sprague-Dawley rats were randomly divided into normal control, autotransplantation (AT) and HP groups. The HP group was subjected to an 8% oxygen atmosphere for 90 minutes before surgery. At 1, 6 and 24 hours after surgery, the rats were killed and their liver tissue was sampled to assess the expression of Bcl-2 protein. The samples were subjected to blood chemistry study, morphological study under a light or transmission electron microscope, and quantitative study of mitochondria. RESULTS: The serum levels of ALT and AST in the HP group were lower than those in the AT group at 1, 6 and 24 hours after orthotopic liver autotransplantation (P < 0.05). Bcl-2 protein expression was increased in the HP group at each measurement point (P < 0.05). Light microscopy showed that hepatic injury in the AT group was much more severe than in the HP group. Hepatocytes in the AT group showed typical apoptosis signs under a transmission electron microscope. The ultrastructural appearance of hepatocytes in the HP group was much better than in the AT group, and the area, perimeter and diameter of the mitochondria were smaller in the HP group than in the AT group (P < 0.05). CONCLUSIONS: Hepatocytes sense and respond to decreased tissue oxygenation. Stimulation by HP relieves apoptosis by upregulating expression of Bcl-2 protein and its protection of mitochondria after orthotopic liver autotransplantation.

Early prevention and treatment of biliary tract complications after orthotopic liver transplantation

OBJECTIVE: To investigate the prevention and treatment of biliary complications after orthotopic liver transplantation (OLT). METHODS: OLT was performed in 18 patients with end-stage liver disease, including 6 patients with primary liver cancer. Except 1 patient was infused only through the portal vein, others were infused through the portal vein and hepatic artery of the donor. The biliary tract was reconstructed using choledochocholedostomic anastomosis in 17 patients, and using Roux-en-Y choledochojejunostomic anastomosis in 1 patient. RESULTS: Four patients with biliary complication were found. In one patient, biliary leakage was found around the T-tube on day 14 postoperatively, and disappeared after re-opening of the tube. In one patient undergoing Roux-en-Y choledochojejunostomic anastomosis, biliary leakage was found on day 12 postoperatively and reoperation was performed. The T-tube was removed from the anastomosis after reoperation, and abdominal infection was controlled, but high fever recurred on day 49 postoperatively. The patient died on day 52 postoperatively. Autopsy revealed biliary leakage and biliary tract necrosis. In another patient, biliary leakage was found on day 3 after operation, and was treated by adequate drainage. Four months after operation, biliary sludge in the common tract was found and treated successfully with oral chemolysis. But biliary sludge or stone recur on one and half year after OLT. Spincterotomy and basket extraction were performed via endoscopic retrograde cholangiopancreatography, and the biliary sludge or stone was cleared out. In case 4, biliary drainage tube cholangiogram showed anastomotic stenosis one month after operation. Three months later, biliary sludge or stone was found beyond anastomotic stenosis. After oral chemolysis (ursodeoxycholic acid) and irrigation with heparinized saline solution via the biliary drainage tube, the biliary sludge disappeared. CONCLUSIONS: To reduce the incidence of biliary complications, adequate infusion of the hepatic artery, complete slushing of the biliary tract, and reduction of injury to the blood supply of the donor biliary tract are essential. Most biliary complications can be treated successfully by non-operative treatment or minimally invasive operation.

T-tube vs no T-tube for biliary tract reconstruction in adult orthotopic liver transplantation:An updated systematic review and metaanalysis

BACKGROUND Whether to use a T-tube for biliary anastomosis during orthotopic liver transplantation(OLT)remains a debatable question.Some surgeons chose to use a T-tube because they believed that it reduces the incidence of biliary strictures.Advances in surgical techniques during the last decades have significantly decreased the overall incidence of postoperative biliary complications.Whether using a T-tube during OLT is still associated with the reduced incidence of biliary strictures needs to be re-evaluated.AIM To provide an updated systematic review and meta-analysis on using a T-tube during adult OLT.METHODS In the electronic databases MEDLINE,PubMed,Scopus,ClinicalTrials.gov,the Cochrane Library,the Cochrane Hepato-Biliary Group Controlled Trails Register,and the Cochrane Central Register of Controlled Trials,we identified 17 studies(eight randomized controlled trials and nine comparative studies)from January 1995 to October 2020.The data of the studies before and after 2010 were separately extracted.We chose the overall biliary complications,bile leaks or fistulas,biliary strictures(anastomotic or non-anastomotic),and cholangitis as outcomes.Odds ratios(ORs)with 95%confidence intervals(CIs)were calculated to describe the results of the outcomes.Furthermore,the test for overall effect(Z)was used to test the difference between OR and 1,where P≤0.05 indicated a significant difference between OR value and 1.RESULTS A total of 1053 subjects before 2010 and 1346 subjects after 2010 were included in this meta-analysis.The pooled results showed that using a T-tube reduced the incidence of postoperative biliary strictures in studies before 2010(P=0.012,OR=0.62,95%CI:0.42-0.90),while the same benefit was not seen in studies after 2010(P=0.60,OR=0.76,95%CI:0.27-2.12).No significant difference in the incidence of overall biliary complications(P=0.37,OR=1.41,95%CI:0.66-2.98),bile leaks(P=0.89,OR=1.04,95%CI:0.63-1.70),and cholangitis(P=0.27,OR=2.00,95%CI:0.59-6.84)was observed between using and not using a T-tube before 2010.However,using a T-tube appeared to increase the incidence of overall biliary complications(P=0.049,OR=1.49,95%CI:1.00-2.22),bile leaks(P=0.048,OR=1.91,95%CI:1.01-3.64),and cholangitis(P=0.02,OR=7.21,95%CI:1.37-38.00)after 2010.A random-effects model was used in biliary strictures(after 2010),overall biliary complications(before 2010),and cholangitis(before 2010)due to their heterogeneity(I2=62.3%,85.4%,and 53.6%,respectively).In the sensitivity analysis(only RCTs included),bile leak(P=0.66)lost the significance after 2010 and a random-effects model was used in overall biliary complications(before 2010),cholangitis(before 2010),bile leaks(after 2010),and biliary strictures(after 2010)because of their heterogeneity(I2=92.2%,65.6%,50.9%,and 80.3%,respectively).CONCLUSION In conclusion,the evidence gathered in our updated meta-analysis showed that the studies published in the last decade did not provide enough evidence to support the routine use of T-tube in adults during OLT.

Establishment of an orthotopic transplantation tumor model of hepatocellular carcinoma in mice

AIM:To improve the outcome of orthotopic transplantation in a mouse model,we used an absorbable gelatin sponge(AGS) in nude mice to establish an orthotopic implantation tumor model.METHODS:MHCC-97L hepatocellular carcinoma(HCC)cells stably expressing the luciferase gene were injected into the subcutaneous region of nude mice.One week later,the ectopic tumors were harvested and transplanted into the left liver lobe of nude mice.The AGS was used to establish the nude mouse orthotopic implantation tumor model.The tumor suppressor gene,paired box gene 5(PAX5),which is a tumor suppressor in HCC,was transfected into HCC cells to validate the model.Tumor growth was measured by bioluminescence imaging technology.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) and histopathology were used to confirm the tumorigenicity of the implanted tumor from the MHCC-97L cell line.RESULTS:We successfully developed an orthotopic transplantation tumor model in nude mice with the use of an AGS.The success rate of tumor transplantation was improved from 60% in the control group to 100% in the experimental group using AGS.The detection of fluorescent signals showed that tumors grew in all live nude mice.The mice were divided into 3 groups:AGS-,AGS+/PAX5-and AGS+/PAX5 +.Tumor size was significantly smaller in PAX5 transfected nude mice compared to control mice(P < 0.0001).These fluorescent signal results were consistent with observations made during surgery.Pathologic examination further confirmed that the tissues from the ectopic tumor were HCC.Results from RT-PCR proved that the HCC originated from MHCC-97L cells.CONCLUSION:Using an AGS is a convenient and efficient way of establishing an indirect orthotopic liver transplantation tumor model with a high success rate.

Immunomodulatory effects of mesenchymal stem cells derived from adipose tissues in a rat orthotopic liver transplantation model

BACKGROUND: Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find a safe and effective method for preventing and treating rejection. This study was designed to confirm the immunomodulatory effects of rat mesenchymal stem cells (MSCs) in vitro and investigate the tolerogenic features in a rat model of allogeneic liver transplantation. METHODS: MSCs were isolated from adipose tissue of Sprague-Dawley (SD) rats and cultured. In vitro, MSCs were added into a mixed lymphocyte culture (MLC) system to study the inhibitory effects of MSCs on the proliferation of T lymphocytes in Wistar rats. By using SD and Wistar rats as liver donors and recipients, an orthotopic liver transplantation model was established and the rats were divided into a MSC-treated group and a blank control group. On postoperative day 7, all rats were sacrificed, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), interleukin-2 (IL-2) and interleukin-10 (IL-10) were measured. The pathological changes of liver tissue and apoptosis of hepatocytes were also assessed. RESULTS: In in vitro MLC, T lymphocyte proliferation in Wistar rats was significantly inhibited by 48.44%. In the MSC-treated group, the levels of ALT, AST, TBIL, IL-2 and IL-10 were 134.2 +/- 45.0 U/L, 162.5 +/- 30.5 U/L, 30.6 +/- 5.4 mu mol/L, 187.35 +/- 18.26 mu g/L and 193.95 +/- 37.62 mu g/L, and those in the blank control group were 355.6 +/- 54.3 U/L, 296.4 +/- 71.2 U/L, 145.7 +/- 28.6 +/- mol/L, 295.73 +/- 57.15 mu g/L and 75.12 +/- 11.23 mu g/L, respectively, with statistically significant differences (P<0.05). Pathological examination revealed that the rejection in the MSC-treated group was clearly alleviated compared with that in the blank control group. TUNEL indicated that the apoptosis of hepatocytes in the MSC-treated group was milder than that in the blank control group (P<0.05). CONCLUSION: Adipose-derived MSCs clearly inhibit recipient-derived T lymphocyte proliferation in MLC and significantly alleviate acute rejection following orthotopic liver transplantation in rats.

Radiofrequency ablation of recurrent cholangiocarcinoma after orthotopic liver transplantation—a case report

AIM: To report the use of radiofrequency ablation in the treatment of recurrenct cholangiocarcinoma in the transplanted liver.METHODS: A lady who underwent orthotopic liver transplantation (OLT) for intrahepatic cholangiocarcinoma recurrence of tumour 13 mo after tralsplantation inspite of adjuvant chemotherapy. Her recurrent tumour was treated with radiofrequency ablation.RESULTS: She survived for 18 mo following the recurrence of her tumour.CONCLUSION: Radiofrequency ablation can be used safely in the transplanted liver to treat recurrent tumour.

Liver biochemistry profile,significance and endoscopic management of biliary tract complications post orthotopic liver transplantation

AIM： To correlate the significance of liver biochemical tests in diagnosing post orthotopic liver transplantation （OLT） biliary complications and to study their profile before and after endoscopic therapy.METHODS： Patients who developed biliary complications were analysed in detail for the clinical information, laboratory tests, treatment offered, response to it, follow up and outcomes. The profile of liver enzymes was determined. The safety, efficacy and outcomes of endoscopic retrograde cholangiography （ERC） were also analysed. RESULTS： 40 patients required ERC for 70 biliary complications. GGT was found to be 〉 3 times （388.1 ± 70.9 U/mL vs 168.5 4± 34.2 U/L, P = 0.007） and SAP 〉 2 times （345.1 ± 59.1 U/L vs 152.7 ± 21.4 U/L, P = 0.003） the immediate post OLT values. Most frequent complication was isolated anastomotic res in 28 （40%）. Sustained success was achieved in 26 （81%） patients. CONCLUSION： Biliary complications still remain an important problem post OLT. SAP and GGT can be used as early, non-invasive markers for diagnosis and also to assess the adequacy of therapy. Endoscopic management is usually effective in treating the majority of these biliary complications.

Postreperfusion syndrome during orthotopic liver transplantation:a single-center experience

BACKGROUND: Marked hemodynamic alteration, commonly referred to as postreperfusion syndrome (PRS), often occurs after revascularization of the donor organ during orthotopic liver transplantation (OLT) and is associated with poor outcomes. This study aimed to investigate the incidence, predictive factors and clinical outcomes of PRS in Chinese patients following OLT at a liver transplantation center in China. METHODS: Over a 5-year period, 330 consecutive patients who had undergone OLT for hepatocellular carcinoma or cirrhosis were included in this retrospective study. PRS was defined as a >30% decrease in the mean arterial pressure compared with that before revascularization for more than 1 minute during the first 5 minutes of graft reperfusion. The patients were divided into 2 groups according to the development of PRS: group 1 (patients with PRS, n=56) and group 2 (patients without PRS, n=274). The demographic characteristics, operative and postoperative courses, and outcomes of the patients were analyzed using SPSS version 18.0. RESULTS: Multivariate regression analysis showed that left ventricular diastolic dysfunction determined by echocardiography and prolonged cold ischemia time were the independent risk factors for PRS. More patients in group 1 showed postoperative renal dysfunction than those in group 2 (19.23% vs 8.4%). Moreover, patients in group 1 also had higher intraoperative (7.14% vs 0%) and postoperative mortalities (26.92% vs 12.04%).CONCLUSION: Left ventricular diastolic dysfunction and prolonged cold ischemia time contribute to a high incidence of PRS, which is associated with adverse outcomes in Chinese patients following OLT.

Dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation in humans

Objective： To compare the dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation （OLT） in humans. Methods： Twenty male patients undergoing liver transplantation were randomly assigned to two comparable groups of 10 patients each to receive a continuous infusion of rocuronium or atracurium under intravenous balanced anesthesia. The response of adductor pollicis to train-of-four （TOF） stimulation of unlar nerve was monitored. The infusion rates of rocuronium and atracurium were adjusted to maintain Tl/Tc ratio of 2%-10%. The total dose of each drug given during each of the three phases of OLT was recorded. Results： Rocuronium requirement, which were （0.468±0.167）mg/（kg·h） during the paleohepatic phase, decreased significantly during the anhepatic phase to （0.303±0.134）mg/（kg·h） and returned to the initial values at the neohepatic period （（0.429±0.130） mg/（kg·h））; whereas atracuruim requirements remained unchanged during orthotopic liver transplantation. Conclusions： This study showed that the exclusion of the liver from the circulation results in the significantly reduced requirement of rocuronium while the requirement of atracurium was not changed, which suggests that the liver is of major importance in the clearance of rocuronium. A continuous infusion of atracurium with constant rate can provide stable neuromuscular blockade during the three stages of OLT.

The scoring system for patients with severe sepsis after orthotopic liver transplantation

BACKGROUND: Because of the complicated pathological features after liver transplantation, severe sepsis is difficult to treat and often leads to death. This study was undertaken to analyze the role of orthotopic liver transplantation (OLT) in patients with severe sepsis and to evaluate the effect of the scoring system. METHODS: Fifty-six patients conformed to the inclusion criteria. They were divided into two groups: non-OLT group (group A) and OLT group (group B). Besides the general data of the patients, the surveillance of blood lactate, the number of failed organs, acute physiology and chronic health evaluationⅡ(APACHEⅡ) and mutiple organ dysfunction score (MODS) were evaluated at the 1st, 3rd and 7th day after OLT. RESULTS: The mortality during hospitalization was 30% in the non-OLT group and 57.6% in the other group. The level of blood lactate at the 1st day of OLT increased more significantly in the OLT group than in the non-OLT group (P<0.01). It was decreased but higher than that in the non-OLT group in the seven days after OLT. The number of failed organs in the OLT group was greater than that in the non-OLT group (P<0.01). The continuous score of APACHEⅡwas not significantly different in the two groups. But the continuous MODS in the OLT group was higher than that in the non-OLT group (P<0.01), which was consistent with the number of failed organs. CONCLUSIONS: The persistently higher level of blood lactate during 7 days may be a dependent risk factor. Immunosuppression may be another risk factor for OLT patients. The mortality of OLT in patients with severe sepsis in 28 days is almost double that in non-OLT patients. The MODS score is better than the APACHEⅡscore in the assessment of organ failure in OLT patients with severe sepsis. The standard scoring system could be improved or a new scoring system that includes the blood lactate score should be established for liver transplantation.

Improved two-cuff technique for orthotopic liver transplantation in rat

BACKGROUND: The first orthotopic liver transplantatio in rat (ROLT) was reported by Lee in 1973. Kamada inno vatively applied cuff technique to ROLT in 1979. However the operative procedures were highly demanding and th operative mortality was relatively high. The purpose of thi study was to improve the model of ROLT, simplify opera tive procedures, and enhance the successful rate of opera tion. METHODS: Orthotopic liver transplantation was per formed in 160 Wistar rats by improved two-cuff technique The portal vein between donor and recipient was anasto mosed with the cuff technique. The same method was use to anastomose the infrahepatic vena cava. The suprahepati vena cava and the hepatic artery were anastomosed by m crovascular suturing and the bile duct was anastomosed en to end by a Teflon catheter. RESULTS: The average time for donor operation, graf preparation and anhepatic phase was 31 minutes, 14 mi nutes and 13 minutes, respectively. The anastomosis tim for the suprahepatic vena cava, portal vein, infrahepatic ve na cava, hepatic artery and bile duct was 7 minutes, 2 mi nutes, 2 minutes, 8 minutes and 1 minute, respectively The main causes for operative mortality were pneumotho rax, anesthesia, air embolism and massive bleeding, an the successful rate of operation was 92.5%. The causes fo death after operation were stoma bleeding, infection, b liary obstruction and graft failure. CONCLUSION: The improved two-cuff technique can re duce operative mortality, enhance survival rate, and serv as an ideal method for the establishment of animal model o ROLT.