A novel nomogram to predict the recurrence of hepatocellular carcinoma after liver transplantation using extended selection criteria.

BACKGROUND: Liver transplantations (LTs) with extended criteria have produced surgical results comparable to those obtained with traditional standards. However, it is not sufficient to predict hepatocellular carcinoma (HCC) recurrence after LT according to morphological criteria alone. The present study aimed to construct a nomogram for predicting HCC recurrence after LT using extended selection criteria. METHODS: Retrospective data on patients with HCC, including pathology, serological markers and follow-up data, were collected from January 2015 to April 2020 at Huashan Hospital, Fudan University, Shanghai, China. Logistic least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were performed to identify and construct the prognostic nomogram. Receiver operating characteristic (ROC) curves, Kaplan-Meier curves, decision curve analyses (DCAs), calibration diagrams, net reclassification indices (NRIs) and integrated discrimination improvement (IDI) values were used to assess the prognostic capacity of the nomogram. RESULTS: A total of 301 patients with HCC who underwent LT were enrolled in the study. The nomogram was constructed, and the ROC curve showed good performance in predicting survival in both the development set (2/3) and the validation set (1/3) (the area under the curve reached 0.748 and 0.716, respectively). According to the median value of the risk score, the patients were categorized into the high- and low-risk groups, which had significantly different recurrence-free survival (RFS) rates (P < 0.01). Compared with the Milan criteria and University of California San Francisco (UCSF) criteria, DCA revealed that the new nomogram model had the best net benefit in predicting 1-, 3- and 5-year RFS. The nomogram performed well for calibration, NRI and IDI improvement. CONCLUSIONS: The nomogram, based on the Milan criteria and serological markers, showed good accuracy in predicting the recurrence of HCC after LT using extended selection criteria.

Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges.

Hepatectomy is still the major curative treatment for patients with liver malignancies. However, it is still a big challenge to remove the tumors in the central posterior area, especially if their location involves the retrohepatic inferior vena cava and hepatic veins. Ex vivo liver resection and auto-transplantation (ELRA), a hybrid technique of the traditional liver resection and transplantation, has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation. Due to its technical difficulty, ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation. The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases, especially in the advanced alveolar echinococcosis. Recently, the application of ELRA for liver malignances has gained more attention. However, standardization of clinical practice norms and international consensus are still lacking. The prognostic impact in these oncologic patients also needs further evaluation. In this review, we summarized the principles and recent progresses on ELRA.

Short-term postoperative bacteriobilia or fungibilia in liver transplantation patients with donation after circulatory death allografts associated with a longer hospital stay: A single-center retrospective observational study in China.

BACKGROUND: Normal bile is sterile. Studies have shown that cholangitis after liver transplantation (LT) was associated with a relatively poor prognosis. It remains unclear whether the bacteriobilia or fungibilia impact the patient outcomes in LT recipients, especially with donation after circulatory death (DCD) allografts, which was correlated with a higher risk of allograft failure. METHODS: This retrospective study included 139 LT recipients of DCD grafts from 2019 to 2021. All patients were divided into two groups according to the presence or absence of bacteriobilia or fungibilia. The prevalence and microbial spectrum of postoperative bacteriobilia or fungibilia and its possible association with outcomes, especially hospital stay were analyzed. RESULTS: Totally 135 and 171 organisms were isolated at weeks 1 and 2, respectively. Among all patients included in this analysis, 83 (59.7%) developed bacteriobilia or fungibilia within 2 weeks post-transplantation. The occurrence of bacteriobilia or fungibilia (ß = 7.43, 95% CI: 0.02 to 14.82, P = 0.049), particularly the detection of Pseudomonas (ß = 18.84, 95% CI: 6.51 to 31.07, P = 0.003) within 2 weeks post-transplantation was associated with a longer hospital stay. However, it did not affect the graft and patient survival. CONCLUSIONS: The occurrence of bacteriobilia or fungibilia, particularly Pseudomonas within 2 weeks post-transplantation, could influence the recovery of liver function and was associated with prolonged hospital stay but not the graft and patient survival.

The AGH score is a predictor of disease-free survival and targeted therapy efficacy after liver transplantation in patients with hepatocellular carcinoma.

BACKGROUND: Liver transplantation (LT) is the "cure" therapy for patients with hepatocellular carcinoma (HCC). However, some patients encounter HCC recurrence after LT. Unfortunately, there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy. The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population, and to evaluate whether these patients are suitable for adjuvant targeted therapy. METHODS: Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed. RESULTS: A total of 201 patients were included in the study. The multivariate Cox analysis suggested that preoperative alpha-fetoprotein (AFP) > 200 µg/L (HR = 2.666, 95% CI: 1.515-4.690; P = 0.001), glutamyl transferase (GGT) > 96 U/L (HR = 1.807, 95% CI: 1.012-3.224; P = 0.045), and exceeding the Hangzhou criteria (HR = 2.129, 95% CI: 1.158-3.914; P = 0.015) were independent risk factors for poor disease-free survival (DFS) in patients with HCC who underwent LT. We established an AFP-GGT-Hangzhou (AGH) scoring system based on these factors, and divided cases into high-, moderate-, and low-risk groups. The differences in overall survival (OS) and disease-free survival (DFS) rates among the three groups were significant (P < 0.05). The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria, UCSF criteria, Milan criteria, and TNM stage. Only in the high-risk group, we found that lenvatinib significantly improved prognosis compared with that of the control group (P < 0.05). CONCLUSIONS: The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China. Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT.

Left Hepatic Vein Preferential Approach Based on Anatomy Is Safe and Feasible for Laparoscopic Living Donor Left Lateral Sectionectomy.

We assess the safety and feasibility of the left hepatic vein preferential approach (LHVPA) based on left hepatic vein (LHV) anatomy for living donor laparoscopic left lateral sectionectomy (LLLS). Data from 50 donors who underwent LLLS in Huashan Hospital from October 2016 to November 2019 were analyzed retrospectively. On the basis of the classification of the LHV anatomy, the vein was defined as the direct import type, upper branch type, or indirect import type. A subgroup analysis was performed to compare the outcomes between the LHVPA and non-LHVPA groups. All 50 patients underwent pure LLLS. The mean operative duration was 157.5 ± 29.7 minutes. The intraoperative blood loss was 160.4 ± 97.5 mL. No complications more severe than grade 3 occurred. LHVPA was applied in 13 patients, whereas non-LHVPA was applied in 10 patients with the direct import type and upper branch type anatomy. The operative duration was shorter in the LHVPA group than the non-LHVPA group (142.7 ± 22.0 versus 173.0 ± 22.8 minutes; P = 0.01). Intraoperative blood loss was reduced in the LHVPA group compared with the non-LHVPA group (116.2 ± 45.6 versus 170.0 ± 63.3 mL; P = 0.02). The length of the LHV reserved extrahepatically in the LHVPA group was longer than in the non-LHVPA group (4.3 ± 0.2 versus 3.3 ± 0.3 mm; P = 0.01). Fewer reconstructions of the LHV in the direct import type anatomy were required for the LHVPA group than for the non-LHVPA group (0/8 versus 4/6). LHVPA based on the LHV anatomy is recommended in LLLS because it can further increase the safety and the efficiency of surgery for suitable donors.

Diabetes mellitus is a risk factor of acute kidney injury in liver transplantation patients.

BACKGROUND: Diabetes mellitus has become an increasing global health burden with rapid growing prevalence. Patients with diabetes have higher susceptibility to acute kidney injury (AKI). Liver transplantation (LT) predisposes the kidney to injury. However, the association between diabetes and AKI in LT patients remains unclear. METHODS: We conducted a retrospective cohort study examining risk factors for AKI in patients undergone orthotopic LT. Potential risk factors including baseline estimated glomerular filtration rate (eGFR), the model for end-stage liver disease (MELD) score, diabetes, hypertension and intraoperative blood loss were screened. The primary endpoint was AKI occurrence. Multivariate logistic regression was used to analyze the association between potential risk factors and AKI. RESULTS: A total of 291 patients undergone orthotopic LT were included in the present study. Among them, 102 patients (35.05%) developed AKI within 5 days after LT. Diabetes was identified as an independent risk factor for AKI. Patients who developed AKI had worse graft function recovery and higher mortality within 14 days after LT compared to those who did not develop AKI. AKI patients with diabetes had a significant decline of eGFR within the first postoperative year, compared with patients who did not develop AKI and who developed AKI but without diabetes. CONCLUSIONS: Diabetes is an independent risk factor for AKI after orthotopic LT. AKI is associated with delayed graft function recovery and higher mortality in short-term postoperative period. Diabetic patients who developed AKI after LT experience a faster decline of eGFR within the first year after surgery.

Effect evaluation of non-pharmaceutical interventions taken in China to contain the COVID-19 epidemic based on the susceptible-exposed-infected-recovered model.

This paper takes confirmed cases of COVID-19 from January 20 to March 18, 2020 as the sample set to establish the susceptible-exposed-infected-recovered (SEIR) model. By evaluating effects of different non-pharmaceutical interventions (NPIs), the research expects to provide references to other countries for formulating corresponding policies. This article divides all non-pharmaceutical interventions into three types according to their different roles. The results show that type-A and type-B non-pharmaceutical interventions both can delay the timing of large-scale infections of the susceptible population, timing of the number of exposed individuals to peak, and timing of peaking of the number of infected cases, as well as decrease the peak number of exposed cases. Moreover, type-B non-pharmaceutical interventions have more significant effects on susceptible and exposed populations. Type-C non-pharmaceutical interventions for improving the recovery rate of patients are able to effectively reduce the peak number of patients, greatly decrease the slope of the curve for the number of infected cases, substantially improve the recovery rate, and lower the mortality rate; however, these non-pharmaceutical interventions do not greatly delay the timing of the number of infected cases to peak. And based on the above analysis, we proposed some suggestions.

Incidental para-ureteral aggressive angiomyxoma: a rare case report and literature review.

BACKGROUND: Aggressive angiomyxoma (AA) is a rare tumor that typically occurs in the pelvis and perineum, most commonly in women of reproductive age. However, no para-ureteral AA has been reported according to the literature. Case presentation We herein describe the first case of para-ureteral AA. A 62-year-old male presented to our institute in March 2017 with a para-ureteral mass that was 15 mm in diameter incidentally. No symptom was observed and laboratory analysis was unremarkable. Magnetic resonance and computed tomography imaging showed a non-enhancing mass abutting the left ureter without causing obstruction. Laparoscopic resection of the mass was performed without injury to the ureter. Pathologic and immunohistochemical results were consistent with AA. Till now, no recurrence was noticed. CONCLUSIONS: We reported a rare case of para-ureteral AA, along with a literature review. Early diagnosis, proper surgical plan and long-term close follow-up is recommended for its high risk of recurrence and malignant potential.

Infection within 2 weeks before liver transplantation closely related to prognosis of posttransplant infection: A single-center retrospective observational study in China.

BACKGROUND: Infections still represent the main factors influencing morbidity and mortality following liver transplantation. This study aimed to evaluate the incidence and risk factors for infection and survival after liver transplantation. METHODS: We retrospectively examined medical records in 210 liver recipients who underwent liver transplantation between April 2015 and October 2017 in our hospital. Clinical manifestations and results of pathogen detection test were used to define infection. We analyzed the prevalence, risk factors and prognosis of patients with infection. RESULTS: The median follow-up was 214 days; the incidence of infection after liver transplantation was 46.7% (n = 98) which included pneumonia (43.4%), biliary tract infection (21.9%), peritonitis (21.4%) and bloodstream infection (7.6%). Among the pathogens in pneumonia, the most frequently isolated was Acinetobacter baumanii (23.5%) and Klebsiella pneumoniae (21.2%). Model for end-stage liver disease (MELD) score (OR = 1.083, 95% CI: 1.045-1.123; P < 0.001), biliary complication (OR = 4.725, 95% CI: 1.119-19.947; P = 0.035) and duration of drainage tube (OR = 1.040, 95% CI: 1.007-1.074; P = 0.017) were independent risk factors for posttransplant infection. All-cause mortality was 11.0% (n = 23). The prognostic factors for postoperative infection in liver recipients were prior-transplant infection, especially pneumonia within 2 weeks before transplantation. Kaplan-Meier curves of survival showed that recipients within 2 weeks prior infection had a significantly lower cumulative survival rate compared with those without infection (65.2% vs. 90.0%; hazard ratio: 4.480; P < 0.001). CONCLUSIONS: Infection, especially pneumonia within 2 weeks before transplantation, complication with impaired renal function and MELD score after 7 days of transplantation was an independent prognostic factor for postoperative infection in liver transplant recipients.

MicroRNA-144 suppresses the expression of cytokines through targeting RANKL in the matured immune cells.

To investigate whether the microRNA-144 (miR-144) had immune regulation effect on matured immune cells, we firstly used quantitative RT-PCR (qRT-PCR) to detect the expression changes of miR-144 between the matured and immature dendritic cells (DCs), macrophages, and the peripheral blood mononuclear cells (PBMCs). Then we went on inspecting the expression changes of TNF-α, IL-1ß, IL-6 and IL-23 in the matured DCs treated with miR-144 mimics or inhibitors using qRT-PCR, and also performed western blot to test phosphorylation state of ERK, JNK, p38 and p65 in these cells. Next, TargetScan was conducted to forecast the target gene of miR-144, receptor activator for nuclear factor-κB ligand (RANKL), and double luciferase reporter system was applied to research their banding sites. We also determined the expression changes of RANKL in the DCs treated with miR-144 mimics or inhibitors using qRT-PCR and ELISA, respectively. The siRNA of RANKL was synthesized and transfected into DCs to inspect how the immune regulation effect of miR-144 was conducted to inhibit the expression of TNF-α using qRT-PCR, and lastly we used flow cytometry to investigate whether this effect applied to Th17 cells. As results, we found that miR-144 was down-regulated in the matured DCs, macrophages and PBMCs of liver transplantation patients, and the miR-144 mimics could inhibit the expression levels of TNF-α, IL-1ß, IL-6 and IL-23 in the matured DCs. Furthermore, miR-144 interacted with RANKL at position 679-685 of RANKL 3'UTR, and suppressed the translation of RANKL mRNA to realize the negative-regulation. Besides, the silence of RANKL enhanced the suppression effect of miR-144 on TNF-α and this immune regulation effect was applied to Th17 cells, too. In conclusion, this study clearly illustrated that miR-144 could inhibit the expression of cytokine in matured immune cells through suppressing the translation of RANKL mRNA.

A quantitative assessment model of T-cell immune function for predicting risks of infection and rejection during the early stage after liver transplantation.

Although more and more clinical studies indicated that ImmuKnow assay could efficiently assess the immune status of recipients, it still has the challenge to predict the occurrence of clinical adverse events. This study aimed to establish a quantitative assessment model, which could more efficiently predict immune function of T lymphocytes after liver transplantation based on three indexes: CD4+ T lymphocyte count (C), CD4+/CD8+ ratio (R), and ImmuKnow adenosine triphosphate (ATP) value (A). We selected 194 recipients and measured the A, C, and R index every week, then obtained the Fisher linear discriminant functions by SPSS 16.0. Next, we divided the recipients into three groups: infection, stable, and rejection groups according to clinical status. After calculating, the discriminant function, 0.012A + 0.019C + 1.322R (simplified into T = 2A + 3C + 200R), was selected to represent the T-cell-mediated immune function. Based on the model, the optimal cutoff T values for infection and rejection were 1415 (sensitivity = 80%, specificity = 79.9%,AUC = 92.3%) and 1939.5 (sensitivity = 93.9%, specificity = 77.6%, AUC = 88.6%), relatively (p < 0.001). In conclusion, this model may be a more feasible way to evaluate the cellular immune function status in liver transplantation recipients.

Population Pharmacokinetic Modeling Combined With Machine Learning Approach Improved Tacrolimus Trough Concentration Prediction in Chinese Adult Liver Transplant Recipients.

This study aimed to develop and evaluate a population pharmacokinetic (PPK) combined machine learning approach to predict tacrolimus trough concentrations for Chinese adult liver transplant recipients in the early posttransplant period. Tacrolimus trough concentrations were retrospectively collected from routine monitoring records of liver transplant recipients and divided into the training data set (1287 concentrations in 145 recipients) and the test data set (296 concentrations in 36 recipients). A PPK model was first established using NONMEM. Then a machine learning model of Xgboost was adapted to fit the estimated individual pharmacokinetic parameters obtained from the PPK model with Bayesian forecasting. The performance of the final PPK model and Xgboost model was compared in the test data set. In the final PPK model, tacrolimus daily dose, postoperative days, hematocrit, aspartate aminotransferase, and concomitant voriconazole, were identified to significantly influence the clearance. The postoperative days along with hematocrit significantly influence the volume of distribution. In the Xgboost model, the first 5 predictors for predicting the clearance were concomitant with voriconazole, sex, single nucleotide polymorphisms of CYP3A4*1G and CYP3A5*3 in recipients, and tacrolimus daily dose, for the volume of distribution were postoperative days, age, weight, total bilirubin and graft : recipient weight ratio. In the test data set, the Xgboost model showed the minimum median prediction error of tacrolimus concentrations, less than the PPK model with or without Bayesian forecasting. In conclusion, a PPK combined machine learning approach could improve the prediction of tacrolimus concentrations for Chinese adult liver transplant recipients in the early posttransplant period.

Individual dose recommendations for drug interaction between tacrolimus and voriconazole in adult liver transplant recipients: A semiphysiologically based population pharmacokinetic modeling approach.

The magnitude of drug-drug interaction between tacrolimus and voriconazole is highly variable, and individually tailoring the tacrolimus dose when concomitantly administered with voriconazole remains difficult. This study aimed to develop a semiphysiologically based population pharmacokinetic (semi-PBPK) model and a web-based dashboard to identify the dynamic inhibition of tacrolimus metabolism caused by voriconazole and provide individual tacrolimus regimens for Chinese adult liver transplant recipients. A total of 264 tacrolimus concentrations and 146 voriconazole concentrations were prospectively collected from 32 transplant recipients. A semi-PBPK model with physiological compartments including the gut wall, portal vein, and liver was developed using the nonlinear mixed-effects modeling software NONMEM (version 7.4). A web-based dashboard was established in R software (version 3.6.1) to recommend the individual tacrolimus regimens when concomitantly administered with voriconazole. The reversible inhibition of tacrolimus metabolism caused by voriconazole was investigated in both the liver and the gut wall. Moreover, voriconazole could highly inhibit the CYP3A activity in the gut wall more than in the liver. BMI and postoperative days were identified as significant covariates on intrinsic intestinal and hepatic clearance of tacrolimus, respectively. Age and postoperative days were identified as significant covariates on the volume of distribution of voriconazole. The individual tacrolimus regimens when concomitantly administered with voriconazole could be recommended in the dashboard (https://tac-vor-ddi.shinyapps.io/shinyapp3/). In conclusion, the semi-PBPK model successfully described the dynamic inhibition process between tacrolimus and voriconazole, and the web-based dashboard could provide individual tacrolimus regimens when concomitantly administered with voriconazole.

Immune evasion mechanisms and therapeutic strategies in gastric cancer.

Gastric cancer (GC) is a malignancy with a high incidence and mortality. The tumor immune microenvironment plays an important role in promoting cancer development and supports GC progression. Accumulating evidence shows that GC cells can exert versatile mechanisms to remodel the tumor immune microenvironment and induce immune evasion. In this review, we systematically summarize the intricate crosstalk between GC cells and immune cells, including tumor-associated macrophages, neutrophils, myeloid-derived suppressor cells, natural killer cells, effector T cells, regulatory T cells, and B cells. We focus on how GC cells alter these immune cells to create an immunosuppressive microenvironment that protects GC cells from immune attack. We conclude by compiling the latest progression of immune checkpoint inhibitor-based immunotherapies, both alone and in combination with conventional therapies. Anti-cytotoxic T-lymphocyte-associated protein 4 and anti-programmed cell death protein 1/programmed death-ligand 1 therapy alone does not provide substantial clinical benefit for GC treatment. However, the combination of immune checkpoint inhibitors with chemotherapy or targeted therapy has promising survival advantages in refractory and advanced GC patients. This review provides a comprehensive understanding of the immune evasion mechanisms of GC, and highlights promising immunotherapeutic strategies.

Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a high recurrence rate. Accurate prediction of recurrence risk is urgently required for tailoring personalized treatment programs for individual HCC patients in advance. In this study, we analyzed a gene expression dataset from an HCC cohort with 247 samples and identified five genes including ENY2, GPAA1, NDUFA4L2, NEDD9, and NRP1 as the variables for the prediction of HCC recurrence, especially the early recurrence. The Cox model and risks score were validated in two public HCC cohorts (GSE76427 and The Cancer Genome Atlas (TCGA)) and one cohort from Huashan Hospital, which included a total of 641 samples. Moreover, the multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor in the prediction of HCC recurrence. In addition, we found that ENY2, GPAA1, and NDUFA4L2 were significantly upregulated in HCC of the two validation cohorts, and ENY2 had significantly higher expression levels than another four genes in malignant cells, suggesting that ENY2 might play key roles in malignant cells. The cell line analysis revealed that ENY2 could promote cell cycle progression, cell proliferation, migration, and invasion. The functional analysis of the genes correlated with ENY2 revealed that ENY2 might be involved in telomere maintenance, one of the fundamental hallmarks of cancer. In conclusion, our data indicate that ENY2 may regulate the malignant phenotypes of HCC via activating telomere maintenance.

Prospective population pharmacokinetic study of tacrolimus in adult recipients early after liver transplantation: A comparison of Michaelis-Menten and theory-based pharmacokinetic models.

Background and Objective: Tacrolimus, a calcineurin inhibitor widely used as a potent immunosuppressant to prevent graft rejection, exhibits nonlinear kinetics in patients with kidney transplantation and nephrotic syndrome. However, whether nonlinear drug metabolism occurs in adult patients undergoing liver transplantation remains unclear, as do the main underlying mechanisms. Therefore, here we aimed to further confirm the characteristics of nonlinearity through a large sample size, and determine the potential influence of nonlinearity and its possible mechanisms. Methods: In total, 906 trough concentrations from 176 adult patients (150 men/26 women; average age: 50.68 ± 9.71 years, average weight: 64.54 ± 11.85 kg after first liver transplantation) were included in this study. Population pharmacokinetic analysis was performed using NONMEM®. Two modeling strategies, theory-based linear compartmental and nonlinear Michaelis-Menten (MM) models, were evaluated and compared. Potential covariates were screened using a stepwise approach. Bootstrap, prediction-, and simulation-based diagnostics (prediction-corrected visual predictive checks) were performed to determine model stability and predictive performance. Finally, Monte Carlo simulations based on the superior model were conducted to design dosing regimens. Results: Postoperative days (POD), Aspartate aminotransferase (AST), daily tacrolimus dose, triazole antifungal agent (TAF) co-therapy, and recipient CYP3A5*3 genotype constituted the main factors in the theory-based compartmental final model, whereas POD, Total serum bilirubin (TBIL), Haematocrit (HCT), TAF co-therapy, and recipient CYP3A5*3 genotype were important in the nonlinear MM model. The theory-based final model exhibited 234 L h-1 apparent plasma clearance and 11,000 L plasma distribution volume. The maximum dose rate (V max ) of the nonlinear MM model was 6.62 mg day-1; the average concentration at steady state at half-V max (K m ) was 6.46 ng ml-1. The nonlinear MM final model was superior to the theory-based final model and used to propose dosing regimens based on simulations. Conclusion: Our findings demonstrate that saturated tacrolimus concentration-dependent binding to erythrocytes and the influence of daily tacrolimus dose on metabolism may partly contribute to nonlinearity. Further investigation is needed is need to explore the causes of nonlinear pharmacokinetic of tacrolimus. The nonlinear MM model can provide reliable support for tacrolimus dosing optimization and adjustment in adult patients undergoing liver transplantation.

The relationship between adenosine triphosphate within CD4(+) T lymphocytes and acute rejection after liver transplantation.

BACKGROUND: There have been increasing interests in the relationship between CD4(+) T lymphocytes and acute rejection (AR) in transplantation. In this study, we explore the role of CD4(+) T lymphocytes after liver transplantation. METHODS: From February to October 2009, 87 patients underwent liver transplantation. They were divided into the AR group and non-acute rejection (NAR) group, with 56 healthy individuals in the control group. Blood specimens were collected preoperatively and at one, two, and four wk postoperatively for all groups and also on the day when AR occurred and one wk after intravenous glucocorticoid therapy for the AR group. Adenosine triphosphate (ATP) levels were measured using the ImmuKnow™ test kits for immune cell functions. RESULTS: After transplantation, the ATP levels within CD4(+) T lymphocytes were significantly elevated in the two groups when compared with the preoperative levels. It peaked in the AR group and was significantly higher than that of the NAR group (p < 0.05). By ROC curve analysis, the obvious elevation of the ATP value one wk after transplantation had better sensitivity and specificity in diagnosing the AR. The ATP sensitivity rate for early AR was 85.7% and specificity rate 80.9% when the cutoff value was 407 µg/L. The ATP value collected on the day of AR occurrence has apparently positive correlation with the rejection acting index (RAI) (p < 0.01). After the intravenous glucocorticoid therapy, all the ARs were reversed and the ATP value declined significantly compared with the control group and that on the day when AR occurred (p < 0.01). CONCLUSIONS: During the early postoperative period (especially at first week after liver transplantation), the elevation of ATP levels within CD4(+) T lymphocytes has good sensitivity and specificity in diagnosing the AR at early stage. And the degree of AR has positive relationship with ATP value. After the intravenous glucocorticoid therapy, the obvious declination of AR might be used in evaluating the effectiveness of anti-rejection treatment.

Reconstruction of the middle hepatic vein tributary in adult right lobe living donor liver transplantation.

BACKGROUND: In adult-to-adult living donor liver transplantation (LDLT), the use of a right lobe graft without the middle hepatic vein (MHV) can cause hepatic congestion and disturbance of venous drainage. To solve this problem, we successfully used cadaveric venous allografts preserved in 4 °C University of Wisconsin (UW) solution within 10 days as interposition veins for drainage of the paramedian portion of the right lobe in adult LDLT. METHODS: From June 2007 to January 2008, 11 adult LDLT patients received modified right liver grafts. The major MHV tributaries (greater than 5 mm in diameter) of 9 cases were preserved and reconstructed using cadaveric interposition vein allografts that had been stored for 1 to 10 days in 4 °C UW solution. The regeneration of the paramedian sector of the grafts and the patency of the interposition vein allografts were examined by Doppler ultrasonography after the operation. RESULTS: MHV tributaries were reconstructed in 9 recipients. Only 1 recipient died of renal failure and severe pulmonary infection on day 9 after transplantation without any hemiliver venous outflow obstruction. The other 8 recipients achieved long-term survival with a median follow-up of 30 months. The cumulative patency rates of the 8 recipients were 63.63% (7/11), 45.45% (5/11), 45.45% (5/11) and 36.36% (4/11) at 3, 6, 12 and 24 months, respectively. Regeneration of the paramedian sectors was equivalent. CONCLUSION: The cadaveric venous allograft preserved in 4 °C UW solution within 10 days serves as a useful alternative for interposition veins in facilitating implantation of a right lobe graft and guarantees outflow of the MHV.