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.

Intracranial pressure monitoring in the perioperative period of patients with acute liver failure undergoing orthotopic liver transplantation

Acute liver failure(ALF)may result in severe neurological complications caused by cerebral edema and elevated intracranial pressure(ICP).Multiple pathogenic mechanisms explain the elevated ICP,and newer hypotheses have been described.While invasive ICP monitoring(ICPM)may have a role in ALF management,these patients are typically coagulopathic and at risk for intracranial hemorrhage.ICPM is the subject of much debate,and significant heterogeneity exists in clinical practice regarding its use.Contemporary ICPM techniques and coagulopathy reversal strategies may be associated with a lower risk of hemor-rhage;however,most of the evidence is limited by its retrospective nature and relatively small sample size.

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.

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.

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.

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.

Plasma levels of tumor necrotic factor-alpha and interleukin-6, -8 during orthotopic liver transplantation and their relations to postoperative pulmonary complications

BACKGROUND: Pulmonary complications after orthoto- pic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ische- mia and reperfusion are induced by pro-inflammatory cyto- kines. The high level of inflammatory cytokines might ad- ditionally influence pulmonary cappillary fluid filtration. The objectives of this study were to measure the concentra- tions of tumor necrotic factor-alpha (TNF-α), interleukin- 6 (IL-6) and interleukin-8 (IL-8) during OLT and to in- vestigate the relationship between these cytokines and post- operative pulmonary complications. METHODS: Twenty-two patients undergoing OLT were divided into two groups according to whether they had postoperative pulmonary complications: group A consis- ting of 8 patients with postoperative pulmonary complica- tions , and group B consisting of 14 patients without post- operative pulmonary complications. Enzyme-linked im- munoassay (ELISA) was used to determine serum TNF-α, IL-6 and IL-8. Blood samples were taken at the beginning of operation (T0 ), clamping and cross-clamping of the in- ferior cava and portal vein (T1, T2 ), 90 minutes and 3 hours after reperfusion (T3 , T4 ) and 24 hours after opera- tion (T5). RESULTS: The level of PaO2/FiO2 in group A was lower than that in group B ( P <0. 05 ). The concentrations of TNF-α, IL-6 and IL-8 in the two groups increased rapidly at T2 , peaked at T3 , decreased rapidly after T3 until 24 hours after operation. The concentrations of TNF-α, IL-6 and IL-8 in group A were higher than those in group B at T2, T3, and T4(P<0.05). CONCLUSION: After un-clamping of the inferior cava and portal vein, the serum concentrations of TNF-α, IL-6 and IL-8 increased may be related to pulmonary injury after he- patic ischemic reperfusion.

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.

Asymptomatic process of hepatic artery thrombosis in a patient after orthotopic liver transplantation

BACKGROUND: Hepatic artery thrombosis is one of the serious complications after liver transplantation. It wil mostly cause a failure of the transplantation. This case o hepatic artery thrombosis showed a stable clinical course and minimal histological change, and now has been survi ving for 4 years with normal liver function. We investigated the possible causes for asymptomatic hepatic artery throm bosis in one patient after orthotopic liver transplantation ( OLT) and discussed the diagnosis of ischemia of OLT pathologically and clinically. METHODS: Liver function test, color Doppler ultrasono graphy, and hepatic arteriography were performed during the development of hepatic arteriothrombosis. Possible fac- tors for the asymptomatic process of the thrombosis were analyzed. RESULTS: On the 4th postoperative day, thrombosis form ed at the anastomotic stoma of the hepatic artery, and on the 11th postoperative day, the artery was completely oc- cluded. Serial liver biopsies revealed intrahepatic cholesta- sis, hydropic degeneration of hepatocytes, atrophy of the biliary epithelium, and fibrosis in the portal area. Monitor- ing of liver function showed nothing abnormal except ele- vation of γ-GT and ALP levels. On the 71st day after OLT, arteriography demonstrated that the hepatic artery re- mained completely occluded in addition to the establish- ment of collateral circulation and compensation of the por- tal vein. The patient didn' t show any symptoms of arterial thrombosis. CONCLUSION: Collateral circulation and compensation o the portal vein are beneficial to allograft survival and avoidence of retransplantation after thrombosis of the he- patic artery. Color Doppler ultrasonography within 2 weeks after OLT is helpful to the early diagnosis of hepatic arterio- thrombosis.

The value of color Doppler ultrasonography in monitoring normal orthotopic liver transplantation and postoperative complications

OBJECTIVE: To assess the value of color Doppler ultrasonography in monitoring normal orthotopic liver transplantation and postoperative complications. METHODS: Forty-one patients after orthotopic liver transplantation were examined by using color Doppler flow imaging to observe the hepatic blood flow and change of ultrasonography of the hepatic parenchyma and bile duct. The measured indexes included maximum blood flow velocity, time-average blood flow velocity (TAV), resistance index (RI) and diameter of the bile duct. RESULTS: Among 41 patients, 17 (41.5%) suffered from liver transplant rejection. Of the 17 patients, 13 (76.4%) showed decrease of TAV of the portal vein, 15 (88.25%) low-amplitude single-phase serrated wave or negative biphasic wave of the hepatic vein, 9 (52.9%) increased hepatic arterial RI, and 5 (29.4%) slightly dilated bile duct. Sonography showed disappearance of the hepatic artery blood flow around the portal vein in 5 (12.2%) of the 41 patients with hepatic artery thrombosis in the postoperative period. Slight dilatation of the intrahepatic bile duct was found in 3 (7.3%) of the 41 patients in the early postoperational period and it normalized within 2 weeks. Ultrasonography of 20 patients (48.8%) revealed a visible dilatation of the intrahepatic bile duct, which was worsening gradually. The causes of bile duct dilatation included biliary stricture in 2 patients (10%), stone in 15 patients (75%) and others in 3 patients (15%). CONCLUSIONS: Color Doppler ultrasonography is valuable for monitoring normal liver transplantation and postoperative complications.

Functional changes of the heart and lung in perioperative period of orthotopic liver transplantation

Objective: To investigate the variation of functions of the heart and lung during orthotopic liver transplan- tation (OLT). Methods: Pulmonary artery cannula and right radial artery cannula were indewelled before anaesthesia and the parameters of hemodynamics in different pe- riods were monitored. Analysis of variance was used to reveal the variation among the groups. T hypothe- sis test in paired data was used to compare the preop- erative parameters with those in each period during operation and after operation respectively, and to compare the parameters immediately after operation with those in each period after operation respective- ly. Results: During the operation, heart rate increased, but blood pressure decreased significantly at the be- ginning of no-liver period, increased again in a short period and then increased progressively 12 h after op- eration. Pulmonary artery pressure (PAP) increased from before the no-liver period to 60 h after opera- tion. Pulmonary wedge pressure changed in accord- ance with the variation of PAP. Cardiac output was maintained at a high-output level from before opera- tion to 60 h after operation. Systemic vascular resist- ance (SVR) was within the normal limits before op- eration, whereas pulmonary vascular resistance (PVR) was lower than normal. In the no-liver peri- od during the operation, SVR decreased significant- ly. Both SVR and PVR increased progressively and returned to normal postoperatively. Conclusions: The patients undergoing OLT have a high cardiac output and Iow resistance obstacle be- fore and during the operation, and will recover grad- ually after operation. Monitoring hemodynamics during the peri-operative period is of significance in the prevention and treatment of pneumonedema and cardiac functional insufficiency.

Three-dimensional dynamic contrast-enhanced MR angiography for evaluating recipient vessels in orthotopic liver transplantation

BACKGROUND: With the improvement of MR technology, three-dimensional dynamic contrast-enhanced MR angiography (3D-DCE-MRA) may be the optimal vascular imaging method for preoperative evaluation of liver transplantation candidates. This study was undertaken to determine the value of 3D-DCE-MRA in the assessment of recipient vessels in orthotopic liver transplantation (OLT). METHODS: The surgical and pathological records were taken as the 'gold standards'. Eighteen cases of OLT were retrospectively analyzed to assess the image quality of MRA, including the signal-to-noise ratio (SNR) in arteries and veins, depiction of vascular variation and vessel disease, and the accuracy of vascular diameter measurement. RESULTS: 3D-DCE-MRA of 34 cases was carried out before OLT. The rates (excellent and good) showing hepatic arteries and portal vein for 3D-DCE-MRA were 94.1% (32/34) and 88.2% (30/34), respectively. The SNRs of the celiac axis and portal vein measurements from 3D-DCE-MRA were 20.58 +/- 3.74 and 13.43 +/- 4.12, and the mean diameters were 3.4 +/- 0.3 rum and 13.1 +/- 3.2 mm, respectively. There were 5 cases of vessel variation according to the Michel's classification. Of the 34 patients, 18 were compared radiologically and pathologically. The accuracy of depiction of the hepatic artery and portal vein with 3D-DCE-MRA was 100% for both; 3D-DCE-MRA precisely assessed 4 cases of more than moderate stenosis in hepatic arteries, 2 cases of small-caliber hepatic artery, 3 cases of venous stenosis at the second porta hepatis, 6 cases of collateral vasculature, I case of portal vein thrombosis and I case of portal vein aneurysm; all were confirmed pathologically. CONCLUSION: 3D-DCE-MRA may be the first choice for recipient vascular assessment before OLT.

Endoscopic management of biliary complications after orthotopic liver transplantation

BACKGROUND: Biliary complications are a serious problem in patients after liver transplantation and often require reoperation. This study was conducted to summarize the endoscopic diagnosis and management of biliary complications after orthotopic liver transplantation (OLT). METHODS: From December 2000 to November 2003, twelve endoscopic retrograde cholangiopancreatographies(ERCPs) were performed in 7 patients after OLT at Digestive Endoscopic Center of Changhai Hospital in Shanghai, China. The therapeutic maneuvers included endoscopic sphincterotomy (EST), biliary stent placement, balloon and basket extraction, irrigation, and nasobiliary tube placement. A retrospective study was made to determine the types of biliary tract complications after OLT. The success of ERCP and therapeutic maneuvers was also evaluated. RESULTS: Biliary tract complications including biliary stricture, biliary leak, biliary sludge, and stump leak of the cyst duct were treated respectively by endoscopic sphincterotomy with sludge extraction, stricture dilation or endoscopic retrograde biliary drainage. Two of the 3 patients with proximal common bile duct stricture were successfully treated with ERCP and stent placement. Four patients with anastomotic stricture and/without bile leak were treated successfully by dilation and stent placement or endoscopic nosobiliary drainage. No severe ERCP-related complications occurred. CONCLUSIONS: ERCP is an effective and accurate approach for the diagnosis of biliary tract complications after OLT, and placement of a stent is a safe initial treatment for biliary complications after liver transplantation.

Impact of simultaneous splenectomy and orthotopic liver transplantation in patients with end-stage liver diseases and splenic hyperfunction

BACKGROUND:Whether splenectomy can be performed simultaneously during liver transplantation in patients with end-stage liver diseases complicated by hypersplenism remains controversial. This study aimed to compare the impact of simultaneous splenectomy on high-and low-risk liver transplant patients with end-stage liver diseases and severe hypersplenism. METHODS:Forty-two patients with end-stage liver diseases complicated by severe hypersplenism who had undergone orthotopic liver transplantation were enrolled in this study. Splenectomy was performed in 19 of the patients. The 42 patients were grouped according to the risk of liver diseases and operations they received. Patients were considered to be at high-risk if they had at least one of the following conditions: preoperative prothrombin time >5 seconds, portal vein thrombosis, and severe perisplenitis. High-risk patients who had undergone splenectomy were classified into group A, whereas high-risk patients who had not undergone splenectomy were classified into group B. Low-risk patients who had undergone splenectomy were classified into group C, and low-risk patients who had spleen preservation were classified into group D. Operative time, intraoperative blood loss, postoperative bleeding, pulmonary infection, perioperative mortality, and postoperative platelet recovery were analyzed. RESULTS: Operative time and intraoperative blood loss were greater in group A than in groups B-D (P<0.01), but there was no significant difference between groups C and D (P>0.05). In group A, 3 patients had postoperative bleeding, 5 had pulmonary infection, and 2 had perioperative mortality,which was higher than any other group, but postoperative bleeding, pulmonary infection, and perioperative mortality were similar to those in groups C and D. In patients undergoing simultaneous splenectomy, platelet counts recovered within 6 months after surgery. Thrombocytopenia was sustained in 3 of the 23 patients who did not undergo simultaneous splenectomy. CONCLUSION: Splenectomy should be avoided during orthotopic liver transplantation in high-risk patients, but this procedure does not increase the operative risk in low-risk patients and may be a valuable method to ensure good postoperative platelet recovery.

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.

Liver retransplantation for ischemic-type biliary lesions after orthotopic liver transplantation:a clinical report of 66 cases

BACKGROUND: Ischemic-type biliary lesions (ITBLs) play an extremely important role in influencing the long-term survival and quality of life of recipients after orthotopic liver transplantation (OLT). Some patients can be cured by interventional therapies, however others lose their grafts at last and receive liver retransplantation (re-OLT). The aim of this study was to analyze the data of 66 patients who had received re-OLT at our center because of ITBL and to discuss the treatment of ITBL after OLT. METHODS: We retrospectively analyzed 66 re-OLT cases due to ITBL from September 2001 to February 2007 at our center. The Kaplan-Meier method and the Cox-Mantel test were used to identify factors associated with mortality for univariate analysis and multivariate analysis, respectively. RESULTS: Fifty-five of 66 ITBL cases underwent interventional therapies before re-OLT. The actuarial survival at I month and I year for these patients was 83% and 74%, respectively. Prognostic factors for mortality in univariate analysis were model of end-stage liver disease score (MELD) >16.5 (chi(2)=5.856, P=0.016), cold ischemia time >8 hours (chi(2)=6.539, P=0.011), infections (chi(2)=5.550, P=0.018) and complications (chi(2)=12.168, P=0.002) after re-OLT. In the multivariate analysis (Cox regression), the risk factors independently associated with mortality were MELD score >16.5 (RR: 3.140; P=0.035), cold ischemia time >8.2 hours (RR: 0.192; P=0.016) and complications (RR: 3.896, P=0.003). CONCLUSIONS: The incidence of ITBL in China is higher than in other countries. Based on our experience, MELD score, cold ischemia time and complications after re-OLT are risk factors independently associated with mortality in retransplanted ITBL patients.

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.

Prevention of hepatitis B virus reinfection after orthotopic liver transplantation

BACKGROUND: Hepatitis B virus reinfection is an impor-tant problem after liver transplantation. The aim of thisstudy was to discuss the prevention of hepatitis B virus rein-fection following orthotopic liver transplantation.METHODS: Sixty-eight cases of chronic fulminant hepatitisB, end-stage liver cirrhosis, and liver carcinoma complicat-ed with HBV cirrhosis were given anti-viral drugs beforeand after transplantation to prevent hepatitis B virus rein-fection. Lamivudine was administered in 2 patients, lami-vudine + hepatitis B immunoglobulin ( HBIG ) in 63, andadefovir + HBIG in 3. The measurement of serum HBV,HBV DNA, liver biopsy immunohistochemistry and clini-cal study were performed.RESULTS: In 1 of the 2 patients who developed reinfectionafter lamivudine administration, serum HBsAg, HBeAb,HBcAb, HBV DNA were positive and liver biopsy immu-nohistochemistry showed HBsAg phenotype. In 2 of 63 pa-tients who developed reinfection after use of lamivudine +HBIG, serum HBsAg, HBeAb, HBcAb were positive andliver biopsy immunohistochemistry showed HBsAg pheno-type. Serum HBV DNA was positive in one of them.Three patients developed no reinfection with HBV after useof adefovir.CONCLUSIONS: Orthotopic liver transplantation is effectivein the treatment of HBV-infected diseases. Lamivudine +HBIG or adefovir + HBIG could effectively prevent hepatitisB virus reinfection.