Arterial blood pressure waveform in liver transplant surgery possesses variability of morphology reflecting recipients' acuity and predicting short term outcomes.

We investigated clinical information underneath the beat-to-beat fluctuation of the arterial blood pressure (ABP) waveform morphology. We proposed the Dynamical Diffusion Map algorithm (DDMap) to quantify the variability of morphology.  The underlying physiology could be the compensatory mechanisms involving complex interactions between various physiological mechanisms to regulate the cardiovascular system. As a liver transplant surgery contains distinct periods, we investigated its clinical behavior in different surgical steps. Our study used DDmap algorithm, based on unsupervised manifold learning, to obtain a quantitative index for the beat-to-beat variability of morphology. We examined the correlation between the variability of ABP morphology and disease acuity as indicated by Model for End-Stage Liver Disease (MELD) scores, the postoperative laboratory data, and 4 early allograft failure (EAF) scores. Among the 85 enrolled patients, the variability of morphology obtained during the presurgical phase was best correlated with MELD-Na scores. The neohepatic phase variability of morphology was associated with EAF scores as well as postoperative bilirubin levels, international normalized ratio, aspartate aminotransferase levels, and platelet count. Furthermore, variability of morphology presents more associations with the above clinical conditions than the common BP measures and their BP variability indices. The variability of morphology obtained during the presurgical phase is indicative of patient acuity, whereas those during the neohepatic phase are indicative of short-term surgical outcomes.

Optimizing the Safe Washout Period for Liver Transplantation Following Immune Checkpoint Inhibitors with Atezolizumab, Nivolumab, or Pembrolizumab.

BACKGROUND: Using immune checkpoint inhibitors (ICIs) as a downstaging therapy for liver transplantation (LT) has improved outcomes for patients with advanced hepatocellular carcinoma (HCC). However, this therapy carries a risk of post-transplant graft rejection. The washout (WO) period between the last ICI dose and LT seems critical in preventing postoperative rejection. This study aimed to optimize the WO period by balancing tumor burden suppression and rejection prevention using ICIs before LT. METHODS: We reviewed published case reports or series from March 2020 to December 2022 regarding LT for HCC after downstaging or bridge therapy with ICIs and included 4 of our cases. Most patients received atezolizumab, nivolumab, or pembrolizumab; these ICIs shared a half-life of around 28 days. Therefore, we excluded cases without definite WO period data and those using non-atezolizumab/nivolumab/pembrolizumab ICIs and ultimately enrolled 22 patients for analysis. We compared their clinical outcomes and estimated the rejection-free survival for every 0.5 half-life interval. RESULTS: Most study subjects received nivolumab (n = 25). Six patients had severe rejections (nivolumab group, n = 5) and needed rescue management. Of the 6 cases, 1 patient died after rejection, and 2 underwent re-transplantation. The median WO period in these 6 patients was 22 days (IQR: 9-35 days). In addition, we found that a 1.5 half-life (42 days) was the shortest safe WO period associated with significant rejection-free survival (P = .005). CONCLUSIONS: Our results showed that 42 days was the safest WO period before LT for HCC after ICI with atezolizumab, nivolumab, or pembrolizumab.

Long-term outcomes of liver transplantation for alcohol-related liver disease.

BACKGROUND: Liver transplantation (LT) is being increasingly performed for alcohol-related liver disease (ALD). It is unclear whether the increasing frequency of LTs in ALD patients has a negative impact on deceased-donor (DDLT) allocation and whether the current policy of 6 months of abstinence before transplantation effectively prevents recidivism after transplantation or improves long-term outcomes. METHODS: A total of 506 adult LT recipients, including 97 ALD patients, were enrolled. The outcomes of ALD patients were compared with those of non-ALD patients. The 97 ALD patients were further divided into group A (6-month abstinence) and group N (nonabstinence) based on the pretransplant alcohol withdrawal period. The incidence of relapsed drinking and the long-term outcomes were compared between the two groups. RESULTS: The prevalence of LT for ALD significantly increased after 2016 (27.0% vs 14.0%; p < 0.01), but the frequency of DDLT for ALD remained unchanged (22.6% vs 34.1%, p = 0.210). After a median follow-up of 56.9 months, patient survival was comparable between the ALD and non-ALD patients (1, 3, and 5 years posttransplant: 87.6%, 84.3%, and 79.5% vs 82.8%, 76.6%, and 72.2%, respectively; p = 0.396). The results were consistent irrespective of the transplant type and disease severity. In ALD patients, 22 of the 70 (31.4%) patients reported relapsed drinking after transplantation, and the prevalence in group A had a higher tendency than that in group N (38.3% vs 17.4%, p = 0.077). Six months of abstinence or nonabstinence did not result in a survival difference, and de novo malignancies were the leading cause of late patient death in ALD patients. CONCLUSION: LT achieves favorable outcomes for ALD patients. Six months of abstinence pretransplant did not predict the risk of recidivism after transplantation. The high incidence of de novo malignancies in these patients warrants a more comprehensive physical evaluation and better lifestyle modifications to improve long-term outcomes.

Single-Center Experience in Managing Right Liver Grafts From Trifurcation or Independent Right Posterior Portal Vein in Adult Living Donor Liver Transplantation.

BACKGROUND: The right liver graft has sometimes been from the trifurcation portal vein (TPV) or independent right posterior portal vein (IRPPV). Managing these PV anatomies to increase the recipient's survival rate remains challenging. Many published techniques could overcome this problem, such as simple unification venoplasty (SUV), autologous portal Y-graft interposition, conjoined unification venoplasty (CUV) with a baseball-like conduit, and SUV plus circumferential fence-like vein extension. This study reviewed our strategy for managing the right liver grafts from TPV or IRPPV in adult living donor liver transplantation (aLDLT). METHODS: We enrolled the study population who underwent aLDLT using the grafts with TPV or IRPPV at our institute from October 2004 to October 2022. We analyzed the reconstruction methods for these grafts and postoperative PV complications in donors and recipients. RESULTS: During the study period, of 528 aLDLT recipients, we identified 26 donors with TPV (n = 10) or IRPPV (n = 16). Eight grafts from TPV had a single PV orifice. The other 18 grafts had dual right PVs that underwent initial PV management, including SUV (n = 13), recipient's right and left portal veins to graft's dual PVs (n = 2), Y-graft interposition (n = 1), CUV (n = 1) and SUV with fence-like vein extension (n = 1). One SUV graft changed to fence venoplasty due to significant tension for PV anastomosis. The acute right posterior PV thrombus and anterior PV stenosis happened in 2 cases with Y-graft interposition and native PVs direct anastomosis. One donor with TPV had portal vein thrombosis and needed thrombectomy with vein patch repair. CONCLUSIONS: The graft from TPV should be carefully planned. A single PV orifice may be feasible but not always possible. An SUV could cover most IRPPVs, but if the distance between the right anterior and posterior PVs is a problem, CUV would be an alternative method. In addition, SUVs with fence venoplasty could relieve PV anastomosis tension.

The strategy of diminishing age gap effect on different donor-recipient combinations in living donor kidney transplantation.

BACKGROUND: The disparity between kidney donation and the number of uremic patients on the waiting list has increased the demand for older live-donor kidneys (OLK). However, the donor-recipient age gap may have an impact on the recipient's outcome. METHODS: Patients who underwent living donor kidney transplantation at our institute between 2005 and 2019 were enrolled and categorized into four donor-recipient groups according to age (≥50 years and <50 years). The Estimated Post-Transplant Survival (EPTS) score was used to quantify the recipient's condition. Adjusted models analyzed recipient outcomes and related risks among the four groups. RESULTS: Of the 154 pairs of live donors and recipients, OLK did not influence overall or death-censored graft survival. The four donor-recipient combinations had similar recipient outcomes, except it slightly worsened in the "old donor to young recipient" group. The EPTS score (adjusted HR, 1.02; 95% CI, 1.01-1.04; p = 0.014) and rejection (adjusted HR, 4.26; 95% CI, 1.36-13.37; p = 0.013) were significant risk factors for overall and death-censored graft survival, respectively. Recipients with pretransplant diabetes or prior solid organ transplantation could have amplified risk effects. The main causes of graft loss were death in older recipients and chronic rejection in younger recipients. CONCLUSION: OLK is safe for young recipients. Nevertheless, adequate immunosuppression should be maintained to prevent rejection and subsequent graft loss, especially for those receiving second kidney transplantation. In contrast, older recipients should avoid overt immunosuppression and control their comorbidities, such as diabetes-related complications to improve their long-term outcomes.

Safety and long-term outcomes of early liver transplantation for pediatric methylmalonic acidemia patients.

BACKGROUND: LT is a treatment option for MMA patients, but renal function impairment is one of the long-term concerns. The aim of this study was to evaluate the outcomes of early LT in these patients. METHODS: A total of 11 MMA mut-type patients (including 10 mut0 cases and 1 mut-case) who received LT in our institute were reviewed. Their metabolic profiles were compared between the pre/post-transplant periods. Their immunosuppressant and renal function changes after transplantation were assessed. RESULTS: After a mean follow-up of 97.5 ± 38.4 months, there were two deaths, and the actual survival rate was 81.8%. Their metabolic profiles had improved (mean blood ammonia level 366.8 ± 105.5 vs. 53.1 ± 17.4 µg/dl, p < .001; C3/C2 ratio 2.68 ± 0.87 vs. 0.73 ± 0.22, p = .003; mean urine MMA level 920.5 ± 376.6 vs. 196.2 ± 85.4, p = .067), and hospital stays were decreased (78.8 ± 74.5 vs. 7.4 ± 7.0 days/year, p = .009) after transplantation. The mean age at transplant was 1.81 ± 2.02 years old, and nine of these patients received LT before the age of 1.5 years old (early LT). Under prospective immunosuppressant dose reduction, three of these early LT patients discontinued the drug and were sustained for more than 5 years. Most of the patients had a preserved renal function, and no patient is currently on dialysis. CONCLUSIONS: In addition to the improvement in the metabolic parameters, early LT in MMA patients may allow for a dose reduction of the immunosuppressant, and the patient's renal function could be preserved in the long term.

Drug-Drug Interactions With Cyclosporine in the Anti-Hepatitis C Viral PrOD Combination Regimen of Paritaprevir/Ritonavir-Ombitasvir and Dasabuvir in Organ Transplant Recipients With Severe Hepatic Fibrosis or Cirrhosis.

BACKGROUND: The clinical guidelines suggest that the dosing of cyclosporine (CsA), during combination therapy with paritaprevir/ritonavir-ombitasvir and dasabuvir (PrOD), would be only one-fifth of the pre-PrOD total daily dose to be administered once daily. However, this dosing may not be applicable to all patients depending on their clinical condition. This study focuses on the pharmacokinetic dynamics of PrOD with CsA in Asian organ transplant recipients with severe liver fibrosis or cirrhosis who undergo concurrent treatment with PrOD treatment and CsA. The efficacy and safety of PrOD treatment was also evaluated. METHODS: Data from 7 patients obtained between January 2017 and September 2017 were retrospectively analyzed. Determinations of the blood concentrations of CsA were made, whether used as a single treatment or in combination therapy with PrOD. RESULTS: The combination regimen compared with CsA administered alone resulted in a 4.53-fold and 5.52-fold increase in the area under the concentration-time curve from time 0-12 hours (AUC0-12 h) of CsA on days 1 and 15, respectively. In addition, the maximal concentration, time to maximum concentration, and terminal phase elimination half-life (t1/2) of CsA were increased during the combined treatment of PrOD and CsA. The authors proposed reducing the CsA dosage during PrOD treatment to one-seventh of that of the pre-PrOD treatment of the total daily dose to maintain target CsA levels. All patients achieved sustained virologic responses at week 12. There were no episodes of serious adverse events or graft rejections observed. CONCLUSIONS: Although the combination with PrOD significantly affects the pharmacokinetics of CsA, it is effective and safe with regular monitoring of the CsA blood concentrations and appropriate CsA dose adjustment.

Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients.

BACKGROUND: Liver transplantation is the definitive treatment for defined stage hepatocellular carcinoma (HCC) in cirrhotic patients. Loco-regional therapy (LRT) may be considered before transplantation to prevent the disease progression and the patient from dropping out of the waiting list. This study aims to evaluate the impact of repeated pretransplant LRTs on the long-term outcomes in HCC liver transplant recipients. METHODS: Between 2004 and 2019, living donor liver transplantation (LDLT) recipients with viable HCC on the explant livers were enrolled. Uni- and multivariate analysis was performed with the Cox regression model to stratify the risk factors associated with HCC recurrence and patent survival after LDLT. RESULTS: A total of 124 patients were enrolled, in which 65.3% (n = 81) were Barcelona Clinic Liver Cancer classification stage B or D and 89% (n = 110) had advanced fibrosis or cirrhosis on the explanted livers. After a median follow-up of 41 months (IQR: 24-86.5), there were 18 cases (13.7%) of HCC recurrence. Univariate analysis showed that the model of end-stage liver disease and Child-Turcotte-Pugh score, pretransplant alpha-fetoprotein value (>500 ng/ml), repeated pretransplant LRTs (N > 4), increased tumor numbers and maximal size, presence of microvascular invasion, and the histological grading of the tumors are risk factors of inferior outcomes. In multivariate analysis, only repeated pretransplant LRTs (N > 4) had a significant impact on both the overall- and recurrence-free survival. The impact of pretransplant LRT was consistently significant among subgroups based on their LRT episodes (N = 0, 1-4, >4 respectively). CONCLUSION: Repeated LRT for HCC can be associated with the risk of tumor recurrence and inferior patient survival after LDLT in cirrhotic patients. Early referral of those eligible for transplantation may improve the treatment outcomes in these patients.

A comparative study of pancreas transplantation between type 1 and 2 diabetes mellitus.

BACKGROUND: Pancreas transplantation remains the best long-term treatment option to achieve physiological euglycemia and insulin independence in patients with labile diabetes mellitus (DM). It is widely accepted as an optimal procedure for type 1 DM (T1DM), but its application in type 2 DM (T2DM) is not unanimously acknowledged. METHODS: In total, 146 diabetes patients undergoing pancreas transplantation were included in this study. Clinical data and outcomes were compared between the T1DM and T2DM groups. RESULTS: Majority (93%) of the pancreas transplantations in T2DM were for uremic recipients. Complications occurred in 106 (73%) patients, including 70 (48%) with early complications before discharge and 79 (54%) with late complications during follow-up period. Overall, rejection of pancreas graft occurred in 37 (25%) patients. Total rejection rate in T2DM recipients was significantly lower than that in T1DM. The short- and long-term outcomes for endocrine function in terms of fasting blood sugar and hemoglobin A1c levels and graft survival rates are comparable between the T2DM and T1DM groups. CONCLUSIONS: T2DM is not inferior to T1DM after pancreas transplantation in terms of surgical risks, immunological and endocrine outcomes, and graft survival rates. Therefore, pancreas transplantation could be an effective option to treat selected uremic T2DM patients without significant insulin resistance.

First-Pass Arrival Interval of Ultrasound Contrast Medium in the Hepatic Artery and Portal Vein as a Marker for Assessment of Liver Transplant Recipients.

BACKGROUND: This study measures the first-pass arrival times in the hepatic artery and portal vein of the transplanted liver using contrast-enhanced ultrasound (CEUS) and assess its correlation with graft performance in the early posttransplant period. METHODS: This study evaluated 35 liver transplant recipients who underwent CEUS examination within 1 month of transplant surgery. CEUS under contrast-specific harmonic imaging mode were recorded for 60 seconds immediately after intravenous administration of microbubble ultrasound contrast medium (Sonazoid, GE Healthcare, Oslo, Norway). The recorded video clips were reviewed by 2 readers to determine the first-pass arrival times in the hepatic artery and portal vein, and the difference between the 2 was defined as the arterial-portal arrival interval (APAI). Laboratory data on the same date of CEUS examination were collected as indicators to correlate with APAI. RESULTS: The intra- and inter-rater reliability for APAI measurement were excellent, with intraclass correlation coefficients > .95. The mean APAI was 4.5 ± 1.8 seconds (range, 2.0-10.5 seconds). The APAI was positively correlated with the serum total bilirubin level (r = 0.357, P = .035) and negatively correlated with the platelet count (r = -0.354, P = .037). At the 5 second cutoff point, a total serum bilirubin of >8 mg/dL was reported in 5 of 11 patients (45.4%) with APAI of >5 seconds and in only 3 of 24 patients (12.5%) with APAI of <5 seconds (P < .05). CONCLUSIONS: The APAI is a quantitative marker that links the hemodynamics and the clinical status of the liver graft.

Living donor liver transplantation for small infants aged less than 6 months: The experience of a single institute.

PURPOSE: Liver transplantation (LT) for small infants < 6 months old is rare but becoming common as perioperative care improves. In Taiwan, living donor LT (LDLT) has expanded indications but is rarely performed for this age group because of unfavorable outcomes in the literature. We evaluated LDLT outcomes of patients <6 months old. METHODS: We identified infants < 6 months old undergoing LDLT between 2004 and 2019 at our hospital. Variables related to recipients, donors, surgeries, and outcomes were analyzed. RESULTS: Nine patients were identified. Indications for LT were biliary atresia (n = 2), Alagille syndrome (n = 1), protein C deficiency (n = 1), and acute liver failure (n = 5), including two patients with neonatal hemochromatosis, one with herpes simplex hepatitis, one with giant cell hepatitis with autoimmune hemolytic anemia, and one with hemophagocytic lymphohistiocytosis. Median age and weight at LT were 129 days and 4.8 kg, respectively. Graft types included left lateral segment (LLS, n = 4), hyper-reduced LLS (n = 4), and monosegment (n = 1). The median graft-to-recipient weight ratio was 4%. The median follow-up period was 14 months (range, 8 days to 127 months) with two mortalities, and two patients were totally weaned off immunosuppressants. Adjuvant therapies were required for patients with giant cell hepatitis and hemophagocytosis. Preoperative reconstructive imaging for estimating graft thickness facilitated surgical planning. CONCLUSION: Although LDLT is difficult to perform for small infants, outcomes are favorable and mainly dependent on underlying causes in addition to technical innovations.

Safe Strategy to Initiate Total Laparoscopic Donor Right Hepatectomy: A Stepwise Approach From a Laparoscopy-Assisted Method.

BACKGROUND: Total laparoscopic donor right hepatectomy (TLDRH) for adult living liver donors has been reported by a few experienced centers, but with limited cases, its safety and feasibility remain controversial. We report our experience initiating TLDRH using a stepwise approach to gradually convert laparoscopy-assisted donor right hepatectomy (LADRH) to TLDRH. METHODS: We retrospectively analyzed the data of 61 LADRHs, 56 conventional open donor right hepatectomies (CODRHs), and 3 TLDRHs performed between March 2014 and June 2018. RESULTS: There were no significant differences in perioperative outcomes between donors undergoing LADRH and CODRH, except for a slight elevations in the operative time (436.5 vs 392.9 min, p < 0.001) and the graft warm ischemic time (5.4 vs 4.0 min, p < 0.001) in the LADRH group. The recipients' posttransplant one-year survival rates in the LADRH and CODRH groups were also similar (93.2% and 94.6%, p = 0.384). For three donors in whom TLDRH was converted from LADRH in a stepwise manner, the average operative time and blood loss were 570 min and 316.7 ml, respectively. Donors were discharged on postoperative day 10 without any surgical complications. CONCLUSIONS: LADRH can be performed routinely on liver living donors. A stepwise approach could be adopted to "covert" suitable donors from LADRH to a total laparoscopic procedure to maximize donor safety. This strategy is reliable and could be reproduced in most LDLT centers.

Highly effective treatment response and well tolerability by all oral direct acting antivirals for chronic hepatitis C patients post organ transplantation.

BACKGROUND: Immunosuppressant-related acceleration of fibrosis has been documented in chronic hepatitis C (CHC) patients who receive organ transplantation (Tx), and sustained virological response (SVR) rates for these patients by pegylated interferon (IFN)-based therapy are generally poor and associated with unfavorable safety profiles. In addition, IFN treatment varies by patient and poses a high risk of post-renal Tx graft rejection. This study was aimed to investigate the efficacy and safety of all oral direct acting antivirals (DAAs) for CHC patients following organ Tx. METHODS: A total of 32 organ Tx (liver: 17, kidney: 13, kidney then liver: 1, and heart: 1) patients with CHC on an oral DAA (paritaprevir/ritonavir, ombitasvir, and dasabuvir: 11, daclatasvir and asunaprevir: 4, sofosbuvir-based: 17) were enrolled in the study. DAAs regimen was based by genotype/subtype, patient characteristics, drug interaction profiles, and health insurance coverage. RESULTS: Mean patient age was 61.4 ± 9.5 years, 50.0% male, and 15.6% with cirrhosis. Fourteen (43.7%) patients experienced unsuccessful IFN treatment. Genotype distribution was as follows: 1a: 6, 1b: 17, 2: 7, 3: 1, and 6: 1. Mean time between Tx and DAAs therapy was 77.3 ± 11.0 months. Baseline HCV RNA before DAAs was 6.20 ± 0.19 log10 IU/mL. After DAAs, the distribution of week 2 HCV RNA was as follows: <15 IU/mL (53.1%), 15 to 50 IU/mL (15.6%), 50 to 100 IU/mL (6.3%), and >100 IU/mL (25.0%), respectively. The rates of undetectable HCV RNA (<15 IU/mL) at week 4 and end-of-treatment were 93.8% and 100%, respectively. Subjective adverse events during therapy were generally mild, with no treatment terminations. After posttreatment follow-up, all 32 patients (100%) achieved SVR12. CONCLUSION: Highly responsive treatment and favorable tolerability were achieved by all oral DAAs in this difficult-to-treat patient population.

Sphingosine-1-phosphate improves endothelialization with reduction of thrombosis in recellularized human umbilical vein graft by inhibiting syndecan-1 shedding in vitro.

Sphingosine-1-phosphate (S1P) has been known to promote endothelial cell (EC) proliferation and protect Syndecan-1 (SDC1) from shedding, thereby maintaining this antithrombotic signal. In the present study, we investigated the effect of S1P in the construction of a functional tissue-engineered blood vessel by using human endothelial cells and decellularized human umbilical vein (DHUV) scaffolds. Both human umbilical vein endothelial cells (HUVEC) and human cord blood derived endothelial progenitor cells (EPC) were seeded onto the scaffold with or without the S1P treatment. The efficacy of re-cellularization was determined by using the fluorescent marker CellTracker CMFDA and anti-CD31 immunostaining. The antithrombotic effect of S1P was examined by the anti-aggregation tests measuring platelet adherence and clotting time. Finally, we altered the expression of SDC1, a major glycocalyx protein on the endothelial cell surface, using MMP-7 digestion to explore its role using platelet adhesion tests in vitro. The result showed that S1P enhanced the attachment of HUVEC and EPC. Based on the anti-aggregation tests, S1P-treated HUVEC recellularized vessels when grafted showed reduced thrombus formation compared to controls. Our results also identified reduced SDC1 shedding from HUVEC responsible for inhibition of platelet adherence. However, no significant antithrombogenic effect of S1P was observed on EPC. In conclusion, S1P is an effective agent capable of decreasing thrombotic risk in engineered blood vessel grafts. STATEMENT OF SIGNIFICANCE: Sphingosine-1phosphate (S1P) is a low molecular-weight phospholipid mediator that regulates diverse biological activities of endothelial cell, including survival, proliferation, cell barrier integrity, and also influences the development of the vascular system. Based on these characters, we the first time to use it as an additive during the process of a small caliber blood vessel construction by decellularized human umbilical vein and endothelial cell/endothelial progenitor. We further explored the function and mechanism of S1P in promoting revascularization and protection against thrombosis in this tissue engineered vascular grafts. The results showed that S1P could not only accelerate the generation but also reduce thrombus formation of small caliber blood vessel.

Exchange of Partial Liver Transplantation Between Children with Different Non-Cirrhotic Metabolic Liver Diseases: How Do We Arrive There?

Hepatic-based metabolic disorders are characterized by an enzyme deficiency expressed solely or mainly in the liver. They are divided into cirrhotic or non-cirrhotic metabolic liver diseases (NCMLDs), and most of them can be treated by liver transplantation. Because the livers with NCMLDs are usually structurally and functionally normal, the primary aim of the liver graft is to support the deficient enzymes rather than maintaining liver functions. Hence, we hypothesize that the exchange of partial liver grafts by the technique of auxiliary partial orthotopic liver transplantation (APOLT) between patients with 2 different NCMLDs may be feasible to replace the deficient enzymes in each patient. This hypothesis is based on the following conditions: (i) the patients have no chance of undergoing timely liver transplantation, (ii) the symptoms of each NCMLD may be alleviated after exchanging partial liver grafts, and (iii) each graft is anatomically appropriate for APOLT. In addition, we evaluate it with a focus on selection of cases, designing of graft sizes, and surgical techniques for reciprocal APOLT.

Suppressor of cytokine signaling (SOCS) 1 is down-regulated in renal transplant recipients with rejection.

The role of suppressor of cytokine signaling (SOCS) in maintaining the immunotolerance of renal allograft is unknown. To clarify this, peripheral blood mononuclear cells (PBMCs) from renal transplant patients with or without rejection were analyzed for the expression of SOCS family proteins by cell culture, immunoblot, flowcytometry and quantitative reverse transcription-polymerase chain reaction (qPCR). Patients with renal graft rejection expressed lower levels of SOCS1 while those without rejection showed a higher SOCS1 expression in the PBMC either on stimulation or not. In addition, SOCS1 was constitutively expressed in normal individuals as well as renal transplant patients with graft tolerance while patients with rejection exhibited down-regulation of the SOCS1 but not SOCS3. The qPCR tests and flowcytometric measurements have also showed that the reduction of SOCS1 expression in rejection could be quantitatively evaluated. These results have suggested that down-regulation of SOCS1 may be regarded as a biomarker for early detection of renal allograft rejection.

Trends in the use of maintenance immunosuppressive drugs among liver transplant recipients in Taiwan: a nationwide population-based study.

PURPOSE: During the past two decades, many novel immunosuppressive drugs have been approved for transplant recipients. Trends in the use of maintenance immunosuppressants after liver transplantation in Asia are unclear. Thus, we aimed to analyze the prescription trends in maintenance immunosuppressive drugs among liver transplant recipients in Taiwan and compare the results with the trends reported from western countries. METHODS: We conducted a retrospective nationwide population-based study utilizing the National Health Insurance Research Database (NHIRD) to analyze the prescribing patterns of immunosuppressants used in Taiwanese liver transplant recipients from 2000 to 2009. RESULTS: A total of 1686 liver transplant patients and their prescriptions of immunosuppressants were analyzed. The 5-year survival rate of liver transplant recipients was 79.6%. In 2009, the major immunosuppressive therapy among liver transplant recipients was a dual-drug regimen with tacrolimus and mycophenolic acid (57.3%). Among the calcineurin inhibitors (CNI), the use of cyclosporine decreased from 58.9% to 12.5%, while the use of tacrolimus notably increased from 23.3% to 77.5%. The use of azathioprine decreased from 21.3% to 0.4%, while the use of mycophenolic acid increased from 56.1% to 76.5%. Among the mammalian target of rapamycin (mTOR) inhibitors, sirolimus was approved in 2002, and its use increased to 8.7% in 2009. In the first 3 months after liver transplantation, a total of 17 different regimens were used in 2009, compared with seven regimens in 2000. CONCLUSIONS: Although the CNI-based combination obviously remains the major regimen, our results reveal a trend toward individualized immunosuppressive regimens among Taiwanese liver transplant recipients. Copyright © 2016 John Wiley & Sons, Ltd.

Minimization or withdrawal of immunosuppressants in pediatric liver transplant recipients.

BACKGROUND: We aimed to minimize the dose of tacrolimus in pediatric patients undergoing liver transplantation prospectively. METHODS: Pediatric liver transplant recipients with stable graft function >1year (transplant at <1year of age), or 2years (transplant at >1year of age) post transplant were screened. After baseline graft biopsy, patients were enrolled into our protocol for elective tacrolimus dose reduction. Patients were assessed by liver function test and protocol biopsy during and after tacrolimus dose reduction. RESULTS: From January 2011 to December 2012, 16 patients were recruited, of whom 15 completed follow-up at a mean 40.75±5.98months. Six patients were preliminarily weaned off tacrolimus, and five remained tacrolimus-free for more than 2years. Of the 10 patients who were not weaned off tacrolimus, six experienced seven episodes of clinical rejection. Five patients had a reduction in tacrolimus dosage to an undetectable trough level, another five to a trough level <4ng/ml, including one patient who was off the study. At the last patient visit, all of the patients had normal liver function test results with no graft loss. Three patients had low-grade graft fibrosis. The patients with metabolic liver disease (p=0.039) and who were recruited earlier after transplantation (p=0.028) were more likely to be weaned off tacrolimus. CONCLUSION: Tacrolimus withdrawal is feasible in select pediatric liver transplant recipients, and long-term follow-up for these patients is suggested.

Outcomes of kidney transplant tourism and risk factors for de novo urothelial carcinoma.

BACKGROUND: To date, the outcomes of transplant tourism have not been reported extensively. In addition, data about the accuracy of urine cytology for the detection and the role of the BK virus (BKV) in the carcinogenesis of urothelial carcinoma (UC) after renal transplantation are lacking. METHODS: Three hundred seven patients who received deceased donor kidney transplants between January 2003 and December 2009 were retrospectively studied. The clinical parameters and outcomes between the domestic and tourist groups were compared. We also investigated the risk factors and role of BKV in the carcinogenesis of de novo UC by quantitative real-time polymerase chain reaction. RESULTS: The subjects in the tourist group were older at transplantation and had a shorter dialysis time before transplantation. There were significantly higher incidence rates of BKV viruria, Pneumocystis jiroveci pneumonia, and malignancy in the tourist group. Graft and patient survival were superior in the domestic group. A total of 43 cancers were identified, and the most common type of malignancy was UC (23 patients, 53.5%). The tourist group had a significantly higher incidence of tumors. The sensitivity and specificity of urine cytology for detecting UC were 73.9% and 94.7%, respectively. Independent predictors of UC included female sex, use of Chinese herbal medicine, and transplant tourism. Only two patients (8.7%) with UC had detectable BKV. CONCLUSIONS: Transplant tourism was a risk factor for infection and de novo malignancy. Urothelial carcinoma was the most common malignancy after kidney transplantation. Regular screening for the early detection of UC by urine cytology or periodic sonographic surveys is mandatory, especially for those at high risk.

A bidirectional approach for portal vein stent placement in a child with complete portal vein occlusion after living donor liver transplantation.

Delayed PV complications are not rare in pediatric liver transplantation. Although PTPV offers a treatment and minimizes surgical revision, in case of complete PV thrombosis (PVT), the failure rate of PTPV is high. Herein, we report a successful technique of PTPV in a case of complete PVT with a stent placement using a bidirectional approach in a child with living donor liver transplantation.