Adult Liver Transplant Patients Research Articles

Intrinsic or Non-Intrinsic End Stage Liver Disease and its Association with Thromboelastography Based Coagulation States in Patients Undergoing Liver Transplantation: A Retrospective Cohort Study

ObjectivesPerioperative coagulation management in liver transplantation recipients is challenging. Viscoelastic testing with rotational thromboelastography (TEG) can help quantify hemostatic profiles. We aimed to investigate whether the etiology of end stage liver disease, pre-transplant disease severity, or pre-transplant thrombotic or bleeding complications are associated with specific TEG patterns. DesignRetrospective cohort study. SettingSingle quaternary care hospital. Participants1,078 adult liver transplant patients. InterventionsThe primary exposure was the etiology of end stage liver disease classified as either intrinsic or non-intrinsic (e.g., biliary obstruction, or cardiovascular). Secondary exposures were patients’ preoperative MELD score, Child-Pugh class, presence of major preoperative thrombotic complications and major bleeding complications. Measurements and Main ResultsPatients with intrinsic liver disease (84%) showed higher odds of hypocoagulable (OR: 3.70, 95% CI: 1.94-7.07, P<0.0001) and mixed TEG patterns (OR: 4.59, 95% CI: 2.07-10.16, P=0.0002) compared to those with non-intrinsic disease. Increasing MELD correlated with higher odds of hypocoagulable (OR: 1.14, 95% CI: 1.08-1.19, P<0.0001) and mixed TEG patterns (OR: 1.08, 95% CI: 1.03-1.14, P = 0.0036). Child-Pugh class C had higher odds of hypocoagulable (OR: 8.55, 95% CI: 3.26-22.42, P<0.0001) and mixed patterns (OR: 12.48, 95% CI: 3.89-40.03, P<0.0001). Major preoperative thrombotic complications were not associated with specific TEG patterns – although we observed an interaction with liver disease severity. ConclusionsLiver transplantation candidates with intrinsic liver disease tend to exhibit hypocoagulable TEG patterns, while non-intrinsic disease is associated with hypercoagulability. Increasing end stage liver disease severity as evidenced by increasing MELD and higher Child Pugh classification, was also associated with hypocoagulable TEG patterns.

Effect of Hemodynamic Monitoring Systems on Short-Term Outcomes after Living Donor Liver Transplantation

Background and Objectives: To evaluate the effects of the pulse index continuous cardiac output and MostCare Pressure Recording Analytical Method hemodynamic monitoring systems on short-term graft and patient outcomes during living donor liver transplantation in adult patients. Materials and Methods: Overall, 163 adult patients who underwent living donor liver transplantation between January 2018 and March 2022 and met the study inclusion criteria were divided into two groups based on the hemodynamic monitoring systems used during surgery: the MostCare Pressure Recording Analytical Method group (n = 73) and the pulse index continuous cardiac output group (n = 90). The groups were compared with respect to preoperative clinicodemographic features (age, sex, body mass index, graft-to-recipient weight ratio, and Model for End-stage Liver Disease score), intraoperative clinical characteristics, and postoperative biochemical parameters (aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, prothrombin time, international normalized ratio, and platelet count). Results: There were no significant between-group differences with respect to recipient age, sex, body mass index, graft-to-recipient weight ratio, Child, Model for End-stage Liver Disease score, ejection fraction, systolic pulmonary artery pressure, surgery time, anhepatic phase, cold ischemia time, warm ischemia time, erythrocyte suspension use, human albumin use, crystalloid use, urine output, hospital stay, and intensive care unit stay. However, there was a significant difference in fresh frozen plasma use (p &lt; 0.001) and platelet use (p = 0.037). Conclusions: The clinical and biochemical outcomes are not significantly different between pulse index continuous cardiac output and MostCare Pressure Recording Analytical Method as hemodynamic monitoring systems in living donor liver transplantation. However, the MostCare Pressure Recording Analytical Method is more economical and minimally invasive.

Risk Factors for Unplanned Readmission in Adult Liver Transplant Patients: A Retrospective Study

IntroductionUnplanned readmission is an important indicator for evaluating medical care quality. Adult liver transplant patients have high risk for readmission, which seriously affects their recovery. As there is currently a lack of research on risk factors for unplanned readmission of adult liver transplant patients in China, the purpose of this study was to elucidate such risk factors. MethodsData for patients undergoing liver transplantation surgery at a tertiary hospital in Zhejiang Province from March 2018 to July 2022 were retrospectively collected. Patients were divided into readmission and nonreadmission groups based on whether unplanned readmission occurred within 90 days. Univariate analysis and logistic regression were used to analyze risk factors for unplanned readmission. ResultsIn total, 123 adult liver transplant patients were included; 38 had unplanned readmission, for a rate of 30.8%. There was a statistically significant difference between the groups in terms of age, educational level, operation time, intraoperative bleeding volume, number of complications, postoperative hospital stay, and hemoglobin (P < .05). Logistic regression analysis showed that age [OR = 1.085, 95% CI (1.022, 1.152)], operation time [OR = 1.010, 95% CI (1.001, 1.020)], postoperative hospital stay [OR = 1.124, 95% CI (1.023, 1.235)], and number of complications [OR = 4.487, 95% CI (1.234, 16.319)] were independent risk factors for unplanned readmission in adult liver transplant patients (P < .05). ConclusionsThe current situation of unplanned readmission for adult liver transplant patients cannot be ignored, indicating that staff should identify risk factors for unplanned readmission as soon as possible and take targeted personalized measures and health education to reduce readmission risk.

Prediction of hepatic artery occlusion after liver transplantation by ultrasound characteristics and clinical risk factors.

Hepatic artery occlusion (HAO) after liver transplantation (LT) is a devastating complication, resulting in early graft loss and reduced overall survival. Ultrasound is an established assessment method for HAO in patients following LT, especially those with complex hepatic artery reconstruction. To investigate the ultrasound characteristics and analyze the risk factors associated with HAO in patients after LT. We retrospectively analyzed the ultrasound characteristics and the clinic risk factors associated with HAO in 400 adult LT patients who were enrolled and treated at the Third People's Hospital of Shenzhen between November 2016 and July 2022. Fourteen patients diagnosed with acute HAO (A-HAO) by surgery and fifteen diagnosed with chronic HAO (C-HAO) were included. A control group of 33 patients without HAO complications during the same period were randomly selected using a random number table. All patients underwent an ultrasonography examination. Parameters including resistance index (RI), peak systolic velocity (PSV), and portal vein velocity (PVV) were compared across the groups. Additionally, basic clinical data were collected for all patients, including gender, age, primary diagnosis, D-dimer concentration, total operation time, cold ischemia time, hot ischemia time, intraoperative blood loss and transfusion, intraoperative urine volume, infusion, model for end-stage liver disease (MELD) score, and whether complex hepatic artery reconstructions were performed. Furthermore, risk factors influencing HAO formation after LT were analyzed. Compared to the non-HAO group, PVV and RI were higher in the A-HAO group, while PSV was lower. Conversely, both PSV and RI were lower in the C-HAO group compared to the non-HAO group. The proportion of patients undergoing complex hepatic artery reconstructions and the gamma-glutamyltransferase (GGT) level before occlusion were significantly higher in the A-HAO group compared to the non-HAO group. However, there were no distinct differences between the two groups in D-dimer, MELD score, pre-occlusion alanine transaminase and aspartate transaminase levels, or intraoperative conditions. Ultrasound features of the hepatic artery before occlusion are significantly associated with postoperative HAO development. Additionally, complex hepatic artery reconstructions, defined as revascularization of the graft requiring additional anastomosis between donor hepatic arteries, constitute a risk factor for A-HAO. Besides, abnormal pre-occlusion GGT elevation is an important biochemical indicator. Therefore, ultrasound examination serves as an important tool for screening HAO, especially in patients with the identified risk factors.

Serum Level of Immunosuppressants as a Marker of Effectiveness of Pharmaceutical Education in Solid Organ Transplantation

Solid organ transplantation promotes an increase in the quality of life of those with diseases that compromise the functioning of a specific organ, maximizing graft survival and reducing the need for retransplantation is essential. Post-transplant medication adherence is one of the factors that influence positive clinical outcomes, with this, the importance of pharmacotherapeutic follow-up at the hospital and outpatient level with the clinical pharmacist is addressed. Objectives: To verify the impact of pharmacotherapeutic guidance and follow-up on the compliance of serum levels of calcineurin inhibitors in lung and liver transplant patients. Methods: Descriptive and retrospective study with adult liver and lung transplant patients using calcineurin inhibitors, aged over 18 years, between 2018 and 2020. The variation index was calculated through the mean and standard deviation of serum levels collected during the index hospitalization, being used to assess the adequacy of serum levels in three different periods. Results: A total of 84 patients were transplanted, including 64 patients (45 liver transplants and 19 lung transplants). In a subgroup analysis, 42.22% of the liver patients and 47.37% of the lung transplant recipients did not have the same serum level in the first post-discharge consultation. After 1 year of transplantation and differentiated outpatient follow-ups, the target serum levels were reached in 63.16% and 77.78% of the studied populations, respectively. Conclusion: The importance of clinical action was demonstrated from the reflection obtained on the adequacy and conformity of serum levels of calcineurin inhibitors, not only at the hospital level but mainly on the pharmacotherapeutic follow-up carried out on an outpatient basis, in which we observed a more expressive value.

Clinical characteristics of new-onset diabetes after liver transplantation and outcomes.

We aimed to identify the characteristics of new-onset diabetes after liver transplantation (LT) (NODAT) and investigate its impacts on post-transplant outcomes. Adult LT patients between 2014 and 2020 who used tacrolimus as initial immunosuppression and survived 3 months at least were evaluated. Patients who developed NODAT within 3 months after LT were classified as NODAT group. Also, patients were further classified as history of diabetes before LT (PHDBT) and non-diabetes (ND) groups. Patient characteristics, post-LT outcomes, and cardiovascular and/or pulmonary complications were compared. A total of 83, 225, and 263 patients were classified into NODAT, PHDBT, and ND groups. The proportion of cholestatic liver disease and rejection within 90 days were higher in NODAT group. Mean serum tacrolimus concentration trough level in the first week after LT was 7.12, 6.12, and 6.12 ng/mL (p < 0.001). Duration of corticosteroids was significantly longer in NODAT compared to PHDBD or ND (416, 289, and 228 days, p < 0.001). Three-year graft and patient survival were significantly worse in NODAT than ND (80.5% vs. 95.0%, p < 0.001: 82.0% vs. 95.4%, p < 0.001) but similar to PHDBT. Adjusted risks of 3-year graft loss and patient death using Cox regression analysis were significantly higher in NODAT compared to ND (adjusted hazard ratio [aHR] 3.41, p = 0.004; aHR 3.61, p = 0.004). Incidence rates of cardiovascular or pulmonary complications after LT in NODAT were significantly higher than ND but similar to PHDBT. Higher initial tacrolimus concentration and early rejection might be risk factors for NODAT. NODAT was associated with worse post-transplant outcomes.

Cost-effectiveness analysis of adult living-donor liver transplantation in Japan.

Living-donor liver transplantation (LDLT) is a highly effective life-saving procedure; however, it requires substantial medical resources, and the cost-effectiveness of LDLT versus conservative management (CM) for adult patients with end-stage liver disease (ESLD) remains unclear in Japan. We performed a cost-effectiveness analysis using the Diagnostic Procedure Combination (DPC) data from the nationwide database of the DPC research group. We selected adult patients (18years or older) who were admitted or discharged between 2010 and 2021 with a diagnosis of ESLD with Child-Pugh class C or B. A decision tree and Markov model were constructed, and all event probabilities were computed in 3-month cycles over a 10-year period. The willingness-to-pay per quality-adjusted life-year (QALY) was set at 5 million Japanese yen (JPY) (49,801 US dollars [USD]) from the perspective of the public health-care payer. After propensity score matching, we identified 1297 and 111,849 patients in the LDLT and CM groups, respectively. The incremental cost-effectiveness ratio for LDLT versus CM for Child-Pugh classes C and B was 2.08 million JPY/QALY (20,708 USD/QALY) and 5.24 million JPY/QALY (52,153 USD/QALY), respectively. The cost-effectiveness acceptability curves showed the probabilities of being below the willingness-to-pay of 49,801 USD/QALY as 95.4% in class C and 48.5% in class B. Tornado diagrams revealed all variables in class C were below 49,801 USD/QALY while their ranges included or exceeded 49,801 USD/QALY in class B. Living-donor liver transplantation for adult patients with Child-Pugh class C was cost-effective compared with CM, whereas LDLT versus CM for class B patients was not cost-effective in Japan.

Predictive Score for Early Successful Tracheal Extubation After Liver Transplant: A Case-Control Study.

Prolonged tracheal intubation and mechanical ventilation after liver transplant increase postoperative complications. Hence, timely extubation should be considered; however, a standard clinical criteria set or scoring system to select patients has not been established for early extubation after livertransplant.We investigated the factors that affect early extubation to design a predictive scoring system for early extubation. This study is a case-control study of adult liver transplant patients. Preoperative, intraoperative, and postoperative clinical data were collected. Early extubation was defined as tracheal extubation immediately or up to 6 hours posttransplant. The variables were compared between the early extubation group and the delayed extubation (>6 hours) group. Our study enrolled 237 patients; among them, 57 patients (24%) were in the early extubation group, and 180 (76%) were in the delayed extubation group. Multiple logistic regression analysis showed that postoperative base excess level at admission to the intensive care unit, number of units of packed red blood cells transfused during surgery, urine volume, and excess base level 6 hours after surgery were the main predictors of successful early extubation. The initial base excess level at the entrance to the intensive care unit(postsurgery) and 6 hours after surgery, packed red blood cell volume transfused during surgery, and urine volume 6 hours after surgery are the main predictors for a successful early tracheal extubation.These factors are considered for the Shiraz Extubation Predictor formula.

Pleural Effusion and Malnutrition Are Associated With Worse Early Outcomes After Liver Transplant.

Pulmonary complications after liver transplantation (LT) have previously been associated with longer hospital stays and ventilator time, and higher mortality. This study reports the outcomes for a specific pulmonary complication, pleural effusion, in LT recipients. Records from a single transplant center were analyzed retrospectively for all adult LT patients. Patients with documented pleural effusion by radiographic imaging within 30 days pre- or post-transplant were considered as cases. Outcomes included length of hospital stay, discharge disposition, hospital readmission, discharge with home oxygen, and 1-year survival. During the 4-year study period, 512 LTs were performed, with 107 patients (21%) developing a peri-transplant pleural effusion. In total, 49 patients (10%) had a pre-transplant effusion, 91 (18%) had a post-transplant effusion, and 32 (6%) had both. Characteristics associated with the presence of any pleural effusion included an increasing model for end-stage liver disease score, re-transplantation, diagnosis of alcoholic liver disease, low protein levels, and sarcopenia. Effusion patients had longer hospital stays (17 vs 9 days, P < .001) and higher likelihood of discharge to a care facility (48% vs 21%, P < .001). Ninety-day readmission occurred in 69% of effusion patients (vs 44%, P < .001). One-year patient survival with any effusion was 86% (vs 94%, P < .01). Overall, 21% of recipients developed a clinically significant peri-transplant pleural effusion. Pleural effusion was associated with worse outcomes for all clinical measures. Risk factors for the development of pleural effusion included higher MELD score (>20), re-transplantation, alcoholic liver disease, and poor nutrition status, including poor muscle mass.

Prediction, prevention, and treatment of post reperfusion syndrome in adult orthotopic liver transplant patients.

This review explores proposed predictors, preventative measures, and treatment options for post-reperfusion syndrome (PRS) in liver transplantation and provides updated data for clinicians. The review aims to understand the status and progress made regarding PRS during orthotopic liver transplantation. Moreover, the predictors of PRS will be analyzed to highlight risk factors. Mediators of PRS and the modes of action of the currently available preventative and management agents that target particular PRS factors will be investigated. Data is drawn from secondary sources from databases of peer-reviewed journals. The bibliographies of select sources were also used to obtain additional data studies using the 'snowball' method. The initial data search provided 1394 studies analyzed using PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. After applying the eligibility criteria, 18 studies were fit for inclusion. The study identified that in addition to the severity of underlying medical conditions, other significant PRS predictors included patient age, sex, duration of cold ischemia, and the surgical technique. While the use of epinephrine and norepinephrine is well-established, further preventative measures commonly involve specifically targeting known mediators of the syndrome, such as antioxidants, vasodilators, free radical scavengers, and anticoagulants. Current management strategies involve supportive therapy. Machine Perfusion may ultimately decrease the risk of PRS. PRS still holds unknowns, including the underlying pathophysiology, controllable factors, and ideal management practices. There is a need for further study, particularly prospective trials since liver transplantation is the gold standard for treating end-stage liver disease and the incidence of PRS remains high.

Patient selection and outcomes of liver transplantation for adult patients with Wilson disease: a single center experience

Shin Hwang, Minjae Kim, Minjae Kim, Chul-Soo Ahn, Deok-Bog Moon, Tae-Yong Ha, Gi-Won Song, Dong-Hwan Jung, Gil-Chun Park, Woo-Hyoung Kang. Korean J Transplant 2022;36:111. https://doi.org/10.4285/ATW2022.F-2306

Lower tacrolimus time in therapeutic range is associated with inferior outcomes in adult liver transplant recipients.

Previous studies on solid organ transplantation have reported that a low time in therapeutic range (TTR) of tacrolimus increases the risk of poor outcomes. However, the reproducibility of the findings in liver transplantation has not yet been confirmed. The TTR, coefficient of variation (CV) and standard deviation (SD) were calculated for 207 adult liver transplant patients from the date of transplantation until the first episode of acute rejection (AR), graft loss, acute kidney injury (AKI), biliary complications, infection or the last follow-up. Kaplan-Meier curves, log-rank tests and Cox regression analyses were performed. Sixty-one (29.5%) patients reached the composite endpoint of AR, biliary complications and graft loss. The log-rank test indicated that the low TTR group had an increased risk of the composite endpoint (P < 0.001), AKI (P < 0.001) and infection (P < 0.001). Multivariate Cox regression analyses revealed that a 10% decrease in TTR was associated with an increased hazard for composite endpoint (hazard ratio [HR]: 1.185, P = 0.010), AKI (HR: 1.355, P < 0.001) and infection (HR: 1.357, P < 0.001). Unexpectedly, SD and CV demonstrated no association with the above-mentioned inferior outcomes. Compared with SD and CV, the TTR of tacrolimus was more correlated with inferior outcomes and may be a novel indicator for predicting the prognosis of liver transplantation.

S91 Management of Biliary Complications in Liver Transplant Recipients Using a Fully Covered Self-expandable Metal Stent With Antimigration Features

Introduction: Following liver transplant (LT) with duct-to-duct anastomosis, biliary strictures and leaks are typically managed with endoscopic retrograde cholangiopancreatography (ERCP) and stenting. While multiple plastic stents are typically used for strictures, self-expandable metal stents (SEMS) can be used to decrease the number of ERCPS with longer periods of stent patency. However, their use is limited by stent migration. The use of fully covered SEMS (FCSEMS), with antimigration fins to manage benign biliary complications following LT may provide stricture resolution with limited adverse events. As such we aimed to describe clinical outcomes of FCSEMS in LT recipients using one type of FCSEMS. Methods: This was a single center retrospective study of consecutive adult LT patients undergoing FCSEMS from January 2014 to April 2022. Primary outcomes were stricture resolution and recurrence. Secondary outcomes included rates of stent migration, stent occlusion, and number of ERCPs required. Results: 46 LT patients with anastomotic strictures (n=40), bile leaks (n=4) or both (n=2) (average age 55.8 years, 33% women) were treated with a FCSEMS with antimigration features (Viabil, W.L. Gore, Flagstaff, AZ) approved for malignant strictures. The median time from LT to FCSEMS placement was 132.5 days. Within one year of LT, 32 patients (69.5%) required intervention; early intervention at less than 30 and 90 days was needed in 7 and 20 patients, respectively. At the time of study conclusion there were 3 patients with stents in situ. Stricture resolution was seen in 34 patients (74%) after an average stent dwell time of 134.5 ± 71 days; recurrence was observed in 8 patients (17%). There were three instances of partial proximal stent migration that did not require reintervention or interfere with removability. Procedural details are listed in Table: The total mean number of ERCPS required was 2.48 (range 1-5). Conclusion: The use of a FCSEMS with antimigration features offers an opportunity to enhance stricture resolution with longer stent dwell times and fewer ERCPs. In our cohort there were no instances of clinically significant stent migration, dysfunction, or procedure related adverse events. Furthermore, these stents provide an opportunity reduce procedure related costs. Additional studies are needed to identify suitable patients for FCSEMS placement. Table 1. - Procedure related details and stent outcomes Stent Dwell Time +/- Standard Deviation (days) 134.5 +/- 71.8 Stent Placement transpapillary vs intraductally, n (%) 36 (78.3%) vs 10 (21.7%) Prior Sphincterotomy, n (%) 17 (40%) Stricture Recurrence, n (%) 8 (17%) Average Number ERCPs, n (range) 2.48 (1-5) Stent Migration, n (%) 3 (6.5 %) Stent Occlusion, n (%) 8 (17%)

Population pharmacokinetics of everolimus in adult liver transplant patients: Comparison to tacrolimus disposition and extrapolation to pediatrics.

Everolimus has recently been used to prevent graft rejection in liver transplantation and reduces the incidence of kidney dysfunction caused by calcineurin inhibitors. In this study, a population pharmacokinetic analysis was conducted to improve the individualization of everolimus therapy. Japanese post-liver transplant patients whose blood everolimus concentrations were measured between March 2018 and December 2020 were included in this study. A nonlinear mixed-effect modeling program was used to explore covariates that affect everolimus pharmacokinetics. Individual everolimus pharmacokinetic parameters estimated by the post-hoc Bayesian analysis using the final model were compared with the tacrolimus dose per trough concentration (D/C) ratio in each patient. The final model was extrapolated to pediatric liver transplant patients for external evaluation. A total of 937 concentrations from 87 adult patients were used in the model-building process. Everolimus clearance was significantly affected by the estimated glomerular filtration rate, concomitant use of fluconazole, sex, as well as total daily dose of everolimus (TDM effect). The estimated individual apparent clearance of everolimus by the post-hoc Bayesian analysis was moderately correlated with the D/C ratio of tacrolimus in each patient (R2 =0.330, p < 0.0001). The estimation accuracy in pediatric patients was considerably high, except for one infant out of 13 patients. In conclusion, population pharmacokinetic analysis clarified several significant covariates for everolimus pharmacokinetics in liver transplant patients. Everolimus pharmacokinetics moderately correlated with tacrolimus pharmacokinetics and could be extrapolated from adult to pediatric patients by body size correction, except for infants.

Risk factors and management of hepatic artery stenosis post liver transplantation.

Hepatic Artery Stenosis (HAS) after liver transplantation (LT), if untreated, can lead to hepatic artery thrombosis (HAT) that carries significant morbidity. To identify risk factors associated with HAS and determine if endovascular therapy (EVT) reduces the occurrence of HAT. This is a retrospective cohort study of adult LT patients between 2013 and 2018. The primary outcome was development of HAT, and secondary outcomes included graft failure and mortality. Logistic regression was used to ascertain the odds ratio of developing HAS. Outcomes between intervention types were compared with Fisher's-exact test. The odds of HAS doubled in DCD-donor recipients (OR=2.27; P=0.04) and transplants requiring vascular reconstruction for donor arterial variation (OR=2.19, P=0.046). Of the 63 identified HAS patients, 44 underwent EVT, 7 with angioplasty alone, 37 combined with stenting. HAT was not significantly different in those who underwent angioplasty with or without stenting than conservative treatment (P=0.71). However, compared to patients without HAS, patients with HAS had higher odds of biliary stricture and decreased graft and overall patient survival (log-rank P < 0.001 & P=0.019, respectively). HAS is significantly higher in DCD-graft recipients. EVT was not associated with reduction in HAT progression. HAS has poor graft and overall survival.

SAT316 - Trends and causes of etiology in adult liver transplant patients: multicenter study

SAT316 - Trends and causes of etiology in adult liver transplant patients: multicenter study

Intraoperative intracardiac thrombus in liver transplantation: A 9-year retrospective review focusing on treatment and outcomes.

This study characterizes incidence and outcomes surrounding intracardiac thrombosis (ICT) during liver transplantation over 9 years at a single center before and after the routine use of transesophageal echocardiography (TEE). Adult liver transplantation patients from 2011 to 2020 were divided into eras based on routine TEE use. ICTs were identified by querying anesthetic records for search terms. Descriptive statistics included counts and proportions for baseline recipient, donor, intraoperative, and postoperative characteristics. Outcome data were based on date of hospital discharge and date of death. The incidence of ICT increased in the TEE era (2016-2020) compared with the pre-TEE era (2011-2015; 3.7% [25/685] vs. 1.9% [9/491]; p < 0.001). Patients with ICT had significantly higher Model for End-Stage Liver Disease-sodium (MELD-Na) scores, pretransplant hospitalization, malignancy, drug-induced liver injury, hypertension, deep vein thrombosis, reperfusion syndrome, transfused platelets and cryoprecipitate, and use of hemostatic medications. A higher proportion of patients in the ICT group underwent simultaneous liver-kidney transplantation. The patients with ICT were similar, except patients in the pre-TEE era had higher MELD-Na scores and incidences of hepatitis C virus and lower incidences of encephalopathy. In the pre-TEE era, all ICTs presented as intraoperative cardiac arrest, and the 30-day mortality in the setting of ICT was 66.7% (6/9). During the TEE era, 80% of ICTs were diagnosed incidentally or attributed to hemodynamic instability (p=0.002). The 30-day mortality rate was 36% (9/25) in the TEE era (p=0.25). ICT incidence increased in the TEE era, yet the mortality rate was lower, suggesting that routine intraoperative TEE may lead to the early detection of ICT prior to hemodynamic collapse.

The role of extracorporeal membrane oxygenation in adult liver transplant patients: A single-center experience

The role of extracorporeal membrane oxygenation in adult liver transplant patients: A single-center experience

Population pharmacokinetics of tacrolimus in Chinese adult liver transplant patients.

Tacrolimus is widely used in organ transplantation to prevent rejection. However, the narrow therapeutic window and the large inter-and intra-individual variability in the pharmacokinetics (PK) of tacrolimus make it difficult for individualization of dosing. This study aimed at developing a population pharmacokinetic model for estimating the oral clearance of tacrolimus in Chinese liver transplant patients, and identifying factors that contribute to the PK variability of tacrolimus. Data of 151 liver transplant patients who received tacrolimus were analyzed in this study. The population PK model was analyzed and the covariates including population demographic and biochemical characteristics, drug combination, and genetic polymorphism were explored using non-linear mixed-effects modeling approach. A single-compartment population PK model was developed, and the final model was CL/F=(14.6-2.38×cytochrome P450 (CYP) 3A5-3.72×WZC+1.04 × (POD/9)+2.48×COR)×Exp(ηi ), where CYP3A5 was 1 for CYP3A5*3/*3, Wuzhi Capsule (WZC) was 1 when patients took tacrolimus combined with WZC, otherwise it was 0, corticosteroids (COR) was 1when patients take tacrolimus combined with COR, otherwise, it was 0, POD was the post-operative day. Visual inspection and bootstrap indicated that the final model was stable and robust. In this study, we developed the first tacrolimus population PK model in Chinese adult liver transplant patients. We first determined the influence of WZC on tacrolimus in these people, which could provide useful PK information for the drug combination of tacrolimus and WZC. We also revealed the influence of genetic polymorphism of CYP3A5, POD, and a combination of COR on tacrolimus PK. Therefore, these significant factors should be taken into consideration in optimizing dosage regimens.

Population pharmacokinetics and dosage optimisation of tacrolimus coadministration with Wuzhi capsule in adult liver transplant patients

This study aimed to establish a population pharmacokinetic model of tacrolimus coadministration with Wuzhi capsule and optimise the dosage regimen in adult liver transplant patients. Totally 1327 tacrolimus trough concentrations from 116 adult liver transplant patients were obtained for model development. A one-compartment model with first-order absorption and elimination was used to analyse the data, and the final model was internally verified using a goodness-of-fit diagnostic plot, bootstrap methods, and visual prediction test. A total of 29 patients with 250 tacrolimus trough concentrations were used for external validation via prediction-based diagnostics. Additionally, the simulation was used to optimise the recommended dose of tacrolimus and Wuzhi capsules. The estimated apparent clearance and volume of the distribution of tacrolimus were 15.4 L/h and 1210 L, respectively. The tacrolimus daily dose, Wuzhi capsule daily dose, postoperative time, alanine transaminase, haemoglobin, total bilirubin, direct bilirubin, estimated glomerular filtration rate, and urea, concomitant with voriconazole and fluconazole, were identified as significant covariates affecting the pharmacokinetic parameters. Internal and external validation showed that the final model was stable and reliable for predicting performance. The final model could provide guidance for dosage optimisation of tacrolimus coadministered with Wuzhi capsules in adult liver transplantation patients.