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Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT.Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59).During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone (P0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD.Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.

This systematic review and expert panel recommendation aims to answer the question regarding the routine use of T-tubes or abdominal drains to better manage complications and thereby improve outcomes after liver transplantation.Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel to assess the potential risks and benefits of T-tubes and intra-abdominal drainage in liver transplantation (CRD42021243036).Of the 2996 screened records, 33 studies were included in the systematic review, of which 29 (6 RCT) assessed the use of T-tubes and 4 regarding surgical drains. Although some studies reported less strictures when using a T-tube, there was a trend towards more biliary complications with T-tubes, mainly related to biliary leakage. Due to the small number of studies, there was a paucity of evidence on the effect of abdominal drains with no clear benefit for or against the use of drainage. However, one study investigating the open vs. closed circuit drains found a significantly higher incidence of intra-abdominal infections when open-circuit drains were used.Due to the potential risk of biliary leakage and infections, the routine intraoperative insertion of T-tubes is not recommended (Level of Evidence moderate - very low; grade of recommendation strong). However, a T-tube can be considered in cases at risk for biliary stenosis. Due to the scant evidence on abdominal drainage, no change in clinical practice in individual centers is recommended. (Level of Evidence very low; weak recommendation). This article is protected by copyright. All rights reserved.

Introduction Diffuse splanchnic vein thrombosis (DSVT) remains a serious challenge in liver transplantation (LT). Reno-portal anastomosis (RPA) has previously been reported as a valid option for management of patients with DSVT during LT. The aim of this study was to evaluate posttransplant renal function and surgical outcomes of patients with DSVT who underwent RPA during LT. Methods Between January 2005 and December 2017, 1,270 patients underwent LT at our institution, including 16 with DSVT managed with RPA (RPA group). We compared renal function and surgical outcomes in these patients to outcomes in 48 propensity-score (PS) matched patients without thrombosis (control group), using a 1:3 matching model. Results The two groups had similar rates of postoperative portal vein thrombosis (PVT), renal dysfunction as measured by estimated glomerular filtration rate (eGFR), and overall postoperative complications (Clavien grade III), although the RPA group had a higher incidence of postoperative upper gastrointestinal (GI) bleeding (31.3% vs 4.2%; p=0.009) that had no clinical consequence. There were no significant differences in five-year graft and patient survival rates between the groups (p=0.133 and p=0.166, respectively). Conclusion RPA is an established technique in the management of patients with DSVT during LT, with comparable outcomes to patients without thrombosis. Our report is the first to demonstrate similar surgical outcomes, including long-term renal function, in LT recipients with or without RPA.

Background Calcineurin inhibitor (CNI) based immunosuppression in liver transplantation (LTx) is associated with acute and chronic deterioration of kidney function. Delaying CNI initiation by using induction rabbit anti-thymocyte globulin (rATG) may provide kidneys with adequate time to recover from a perioperative insult reducing the risk of early post-LTx renal deterioration. Methods This was an open-label, multicenter, randomized controlled clinical trial comparing use of induction rATG with delayed CNI initiation (day-10) against upfront CNI commencement (SOC; standard of care) in those patients deemed at standard risk of postoperative renal dysfunction following LTx. The primary end point was change in (delta) creatinine from baseline to month-12. Results Fifty-five patients were enrolled in each study arm. Mean Tacrolimus levels remained comparable in both groups from day-10 throughout the study period. A significant difference in delta creatinine was observed between rATG and SOC groups at 9-months (p=0.03) but not at month-12 (p=0.05). eGFR levels remained comparable between cohorts at all time points. Rates of biopsy-proven acute rejection at 1-year were similar between groups (16.3 vs 12.7%, p= 0.58). rATG showed no significant adverse effects. Survival at 12-months was comparable between groups (p= 0.48). Conclusions Although the use of induction rATG and concurrent CNI deferral in this study did not demonstrate a significant difference in delta creatinine at 1 year, these results indicate a potential role for rATG in preserving early kidney function, especially when considered with CNI deferral beyond 10 days and/or lower target Tacrolimus levels, with acceptable safety and treatment efficacy.

The use of livers from donation after circulatory death (DCD) is historically characterized by increased rates of biliary complications and inferior short-term graft survival (GS) compared to donation after brain death (DBD) allografts. This study aimed to evaluate the dynamic prognostic impact of DCD livers to reveal whether they remain an adverse factor even after patients survive a certain period following liver transplant (LT). This study used 74 961 LT patients including 4065 DCD LT in the scientific registry of transplant recipients from 2002-2017. The actual, 1 and 3-year conditional hazard ratio (HR) of 1-year GS in DCD LT were calculated using a conditional version of Cox regression model. The actual 1-, 3-, and 5-year GS of DCD LT recipients were 83.3%, 73.3%, and 66.3%, which were significantly worse than those of DBD (all P

Postcapillary pulmonary hypertension (PH) can be seen in cirrhosis. Research and treatment goals exist for patients with portopulmonary hypertension but not for postcapillary PH. The aim of this study was to investigate outcomes after liver transplant (LT) for patients with postcapillary PH.This was a retrospective cohort study of 1173 patients who underwent LT at our center between 2010 and 2020. Using a propensity score matched analysis followed by multivariable Cox modeling on matched patients, we compared post-LT survival between patients with and without postcapillary PH. We also compared several post-LT outcomes between patient with different types of PH.Sixty-eight patients had PH, and 50 had postcapillary PH. The median age was 59 y and the sample was 54% male. There was no significant difference in mortality between patients with postcapillary PH and patients without PH (hazard ratio, 1.72; 95% confidence interval, 0.90-3.31;Postcapillary PH does not appear to convey a negative impact on post-LT survival. A higher cardiac output may be protective against mortality in patients with postcapillary PH.

Transjugular intrahepatic portosystemic shunt has been established as an effective treatment for complicated portal hypertension. This retrospective study investigated the effect of pretransplant transjugular intrahepatic portosystemic shunt placement on intraoperative graft hemodynamics and surgical outcomes after liver transplantation.Of 1,081 patients who underwent liver transplantation between January 2007 and June 2017 at Cleveland Clinic (OH, USA), 130 patients had transjugular intrahepatic portosystemic shunt placement before liver transplant. We performed a 1:2 propensity score matching to compare intraoperative graft hemodynamics and surgical outcomes between the transjugular intrahepatic portosystemic shunt group (n = 130) and the no-transjugular intrahepatic portosystemic shunt group (n = 260).The transjugular intrahepatic portosystemic shunt did not increase operative time, the volume of blood transfusion, duration of hospital stay, or complication rates. Graft and patient survivals were similar between the groups. Mean intraoperative cardiac output and graft portal flow in the transjugular intrahepatic portosystemic shunt group were greater than in the no-transjugular intrahepatic portosystemic shunt group (P = .03 and P = .003, respectively). In multivariate analysis, male sex, younger age, low platelet count, absence of portal vein thrombosis, and pretransplant transjugular intrahepatic portosystemic shunt placement were independently associated with increased portal flow volume (Por = 0.03 each). Transjugular intrahepatic portosystemic shunt malposition was observed in 17 patients (13.1%). The 1-year patient survival was 70.6% with transjugular intrahepatic portosystemic shunt malposition and 92.0% without transjugular intrahepatic portosystemic shunt malposition (P = .01).Our findings suggest that pretransplant transjugular intrahepatic portosystemic shunt placement increases graft portal flow but does not compromise surgical outcomes after liver transplantation. Transjugular intrahepatic portosystemic shunt malposition, however, is not uncommon and may increase the complexity of transplantation.

Donation after circulatory death (DCD) liver transplantation improves deceased donor liver use and decreases waitlist burden, albeit at an increased risk of biliary complications and inferior graft survival. Employing liver vascular inflow measurements intraoperatively permits allograft prognostication. However, its use in DCD liver transplantation is hitherto largely unknown and further explored here. DCD liver transplantation patient records at a single center from 2005 to 2018 were retrospectively scrutinized. Intraoperative flow data and relevant donor parameters were analyzed against endpoints of biliary events and graft survival. A total of 138 cases were chosen. The incidence of cumulative biliary complications was 38%, the majority of which were anastomotic strictures and managed successfully by endoscopic means. The ischemic cholangiopathy rate was 6%. At median thresholds of a portal vein (PV) flow rate of92 mL/minute/100 g and buffer capacity (BC) of0.04, both variables were independently associated with risk of biliary events (P = 0.01 and 0.04, respectively). Graft survival was 90% at 12 months and 75% at 5 years. Cox regression analysis revealed a PV flow rate of50 mL/minute/100 g as predictive of poorer graft survival (P = 0.01). Furthermore, 126 of these DCD livers were analyzed against a propensity-matched group of 378 contemporaneous donation after brain death liver allografts (1:3), revealing significantly higher rates (P 0.001) of both early allograft dysfunction (70% versus 30%) and biliary complications (37% versus 20%) in the former group. Although flow data were comparable between both sets, PV flow and BC were predictive of biliary events only in the DCD cohort. Intraoperative inflow measurements therefore provide valuable prognostication on biliary/graft outcomes in DCD liver transplantation, can help inform graft surveillance, and its routine use is recommended.

BACKGROUND Rates of withdrawal of life-sustaining treatment are higher among critically ill pediatric patients compared to adults. Therefore, livers from pediatric donation after circulatory death (pDCD) could improve graft organ shortage and waiting time for listed patients. As knowledge on the utilization of pDCD is limited, this study used US national registry data (2002-2017) to estimate the prognostic impact of pDCD in both adult and pediatric liver transplant (LT). METHODS In adult LT, the short-term (1-year) and long-term (overall) graft survival (GS) between pDCD and adult donation after circulatory death (aDCD) grafts was compared. In pediatric LT, the short- and long-term prognostic outcomes of pDCD were compared with other type of grafts (brain dead, split, and living donor). RESULTS Of 80 843 LTs in the study, 8967 (11.1%) were from pediatric donors. Among these, only 443 were pDCD, which were utilized mainly in adult recipients (91.9%). In adult recipients, short- and long-term GS did not differ significantly between pDCD and aDCD grafts (hazard ratio = 0.82 in short term and 0.73 in long term, both P > 0.05, respectively). Even "very young" (≤12 y) pDCD grafts had similar GS to aDCD grafts, although the rate of graft loss from vascular complications was higher in the former (14.0% versus 3.6%, P < 0.01). In pediatric recipients, pDCD grafts showed similar GS with other graft types whereas waiting time for DCD livers was significantly shorter (36.5 d versus 53.0 d, P < 0.01). CONCLUSIONS Given the comparable survival seen to aDCDs, this data show that there is still much scope to improve the utilization of pDCD liver grafts.

Although experimental studies have reported that hepatic ischemia-reperfusion injury promotes tumor growth and metastases, the impact of graft hemodynamics on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is unclear. To investigate the association between graft hemodynamics and HCC recurrence after LT, we conducted a retrospective analysis of 279 patients who underwent LT for HCC. Graft hemodynamics including portal vein flow (PVF), hepatic artery flow (HAF), and total hepatic flow (THF) was analyzed as a predictor of HCC recurrence, using competing risk regression analyses. The cutoff values of PVF, HAF, and THF were set at the lower quartile of distribution. A cumulative recurrence curve demonstrated that low THF (

Coronavirus disease 2019 (COVID‐19), mediated by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), can manifest with flu‐like illness and severe pneumonia with acute respiratory distress syndrome (ARDS). Immunocompromised patients merit particular attention as altered host immunity may influence both disease severity and duration of viral shedding as is described with several other ribonucleic acid respiratory viruses. Yet immunocompromised status alone, in the absence of other comorbidities, may not necessarily predict severe illness presentations and poorer clinical outcomes as indicated by recent reports of COVID‐19‐infected solid organ transplant recipients and people living with human immunodeficiency virus (HIV). Such patients may even be spared the robust inflammatory response that precipitates ARDS associated with COVID‐19, complicating the management of iatrogenic immunosuppression in this setting. We present a case of an orthotopic liver transplant recipient with well‐controlled HIV who successfully recovered from a mild, flu‐like illness attributed to SARS‐CoV‐2.

BACKGROUND Dobutamine stress echocardiography (DSE) is commonly used for cardiovascular assessment before orthotopic liver transplantation (OLT). The coronary artery calcium score (CACS) is a useful screening tool for coronary artery disease (CAD). We aimed to compare the sensitivity and specificity of DSE and CACS for CAD in OLT candidates. MATERIAL AND METHODS A total of 265 of the 1589 patients who underwent OLT at our center between 2008 and 2019 had preoperative coronary angiography (CAG). Of these, 173 had DSE and 133 had a CT scan suitable for CACS calculation within 1 year of OLT. Patients with a nondiagnostic DSE were excluded (n=100). Two reviewers evaluated CACS on CT scans. The sensitivity/specificity of DSE and CACS for detection of angiographically significant CAD were calculated for patients with both tests (n=36). A separate analysis compared the sensitivity/specificity of a diagnostic DSE (n=73) and CACS (n=133) against CAG for all patients with either test. RESULTS Sensitivity and specificity were 57.1% and 89.7%, respectively, for DSE, compared with 71.4% and 62.1% for CACS at ≥100 Agatston score. For the analysis of all patients with either test, the sensitivity/specificity of DSE for detection of CAD and CACS were 30.8% and 85.0% and 80.0% and 62.8%, respectively. On ROC analysis, CACS was a satisfactory predictor of obstructive CAD (AUC, 0.76±0.06, 95% CI, 0.66-0.87; P0.001). CONCLUSIONS CACS may be an important tool for cardiovascular assessment in patients undergoing OLT. DSE was nondiagnostic in a large percentage of OLT candidates, limiting its use in this population.

Tumour morphological criteria for determining the appropriateness of liver transplantation in patients with hepatocellular carcinoma poorly estimate post-transplantation mortality. The aim of this study was to develop and assess the utility of a continuous risk score in predicting overall survival following liver transplantation for hepatocellular carcinoma.We did a retrospective cohort analysis to develop a continuous multivariable risk score for assessment of overall survival following liver transplantation for hepatocellular carcinoma. We used data from 420 patients with hepatocellular carcinoma who underwent liver transplantation between Jan 1, 2002, and Oct 31, 2014, at the Cleveland Clinic Foundation (CCF), Cleveland, OH, USA. The model we developed (Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma; HALT-HCC) assessed the association of the following previously reported variables of interest with overall survival by use of multivariate Cox regression: MELD-sodium (MELD-Na), tumour burden score (TBS), alpha-fetoprotein (AFP), year of transplantation, underlying cause of cirrhosis, neutrophil-lymphocyte ratio, history of locoregional therapy, and Milan criteria status. Once the risk equation was generated, validation and calibration of risk assessment was done with nationwide data for the same time period from the Scientific Registry of Transplant Recipients (SRTR; n=13 717).The risk equation was generated as (1·27 × TBS) + (1·85 × lnAFP) + (0·26 × MELD-Na) and the HALT-HCC score ranged from 2·40 to 46·42 in the CCF cohort. In the validation cohort, prognosis worsened with increasing HALT-HCC score (5-year overall survival of 78·7% [95% CI 76·9-80·4] for quartile 1, 74·5% [72·6-76·2] for quartile 2, 71·8% [70·1-73·5] for quartile 3, and 61·5% [59·6-63·3] for quartile 4; p0·0001). Multivariate Cox modelling showed that HALT-HCC was significantly associated with overall survival (hazard ratio [HR] 1·06 per point, 95% CI 1·05-1·07), even after adjustment for risk factors not related to hepatocellular carcinoma. Assessment of discrimination revealed a C-index of 0·613 (95% CI 0·602-0·623). Calibration coefficients for linear regressions of observed versus predicted mortality were 1·001 (95% CI 0·998-1·007) at 1 year and 0·982 (0·980-0·987) at 2 years after transplantation. Patients within and outside the Milan criteria showed similar risk of death when stratified by HALT-HCC score. Among the 12 754 patients who met the Milan criteria, 2714 were shown to have poor prognosis after transplantation after stratification by HALT-HCC score with a cutoff of 17; conversely, among the 963 patients who did not meet the Milan criteria, 287 had demonstrably good prognosis.The HALT-HCC score might enable clinicians to accurately assess post-transplantation survival in patients with hepatocellular carcinoma by use of individualised, preoperatively assessed characteristics. However, further studies are needed before adoption.None.

Uterus transplantation is the only known potential treatment for absolute uterine factor infertility. It offers a unique setting for the investigation of immunologic adaptations of pregnancy in the context of the pharmacologic-induced tolerance of solid organ transplants, thus providing valuable insights into the early maternal-fetal interface. Until recently, all live births resulting from uterus transplantation involved living donors, with only 1 prior birth from a deceased donor. The Cleveland Clinic clinical trial of uterus transplantation opened in 2015. In 2017, a 35 year old woman with congenital absence of the uterus was matched to a 24 year old parous deceased brain-dead donor. Transplantation of the uterus was performed with vaginal anastomosis and vascular anastomoses bilaterally from internal iliac vessels of the donor to the external iliac vessels of the recipient. Induction and maintenance immunosuppression were achieved and subsequently modified in anticipation of pregnancy 6 months after transplant. Prior to planned embryo transfer, ectocervical biopsy revealed ulceration and a significant diffuse, plasma cell-rich mixed inflammatory cell infiltrate, with histology interpreted as grade 3 rejection suspicious for an antibody-mediated component. Aggressive immunosuppressive regimen targeting both cellular and humoral rejection was initiated. After 3 months of treatment, there was no histologic evidence of rejection, and after 3 months from complete clearance of rejection, an uneventful embryo transfer was performed and a pregnancy was established. At 21 weeks, central placenta previa with accreta was diagnosed. A healthy neonate was delivered by cesarean hysterectomy at 34 weeks' gestation. In summary, this paper highlights the first live birth in North America resulting from a deceased donor uterus transplant. This achievement underscores the capacity of the transplanted uterus to recover from a severe, prolonged rejection and yet produce a viable neonate. This is the first delivery from our ongoing clinical trial in uterus transplantation, including the first reported incidence of severe mixed cellular/humoral rejection as well as the first reported placenta accreta.

OBJECTIVE The objective of this retrospective study was to characterize the neutrophil to lymphocyte ratio (NLR) on the waitlist and determine its prognostic utility in liver transplantation (LT) for hepatocellular carcinoma (HCC) with special focus on longitudinal data. Biomarkers such as pre-operative NLR have been suggested to predict poor oncological outcomes for patients with HCC seeking LT. NLR's utility is thought to be related to tumor biology. However, recent studies have demonstrated that a high NLR conveys worse outcomes in non-HCC cirrhotics. This study investigated the relationship between NLR, liver function, tumor factors and patient prognosis. METHODS Patients with HCC undergoing LT were identified between 2002 and 2014 (n = 422). Variables of interest were collected longitudinally from time of listing until LT. The prognostic utility of NLR was assessed using Kaplan-Meier and Cox Proportional Hazard regression. Associations between NLR and MELD-Na, AFP, and tumor morphology were also assessed. RESULTS NLR demonstrated a positive correlation with MELD-Na at LT (R2 = 0.125, P

Objective Portal vein thrombosis (PVT) does not preclude liver transplantation (LT), but poor portal vein (PV) flow after LT remains a predictor of poor outcomes. Given the physiologic tendency of the hepatic artery (HA) to compensate for low PV flow via vasodilation, we investigated whether adequate HA flow would have a favorable prognostic impact among patients with low PV flow following LT. Methods This study included 163 patients with PVT who underwent LT between 2004 and 2015. PV and HA flow were categorized into quartiles, and their association with 1-year graft survival (GS) and biliary complication rates was assessed. For both the HA and the PV, patients at the lowest two quartiles were categorized as having low flow and the remainder as having high flow. Results The median MELD score was 22 and 1-year GS was 87.3%. As expected, GS paralleled PV flow with patients at the lowest flow quartile faring the worst. In combination of PV and HA flows, high HA flow was associated with improved 1-year GS among patients with low PV flow (P = .03). Similar findings were observed with respect to biliary complication rates. Conclusions Sufficient HA flow may compensate for poor PV flow. Consequently, meticulous HA reconstruction may be central to achieving optimal outcomes in PVT cases.

BACKGROUND While portal flow (PF) plays an important role in determining graft outcomes in living donor liver transplantation, its impact in deceased donor liver transplantation (DDLT) is unclear. The aim of this study was to investigate the correlations between graft PF and graft outcomes in DDLT. METHODS We retrospectively investigated 1001 patients who underwent DDLT between January 2007 and June 2017 at our institution. The patients were divided into 3 groups according to hazard ratio for 1-year graft loss at each PF value, which was standardized with graft weight. Graft and recipient outcomes were compared between the groups. RESULTS The low-PF group (PF < 65 mL/min/100 g, n = 210, P = 0.011) and the high-PF group (PF ≥ 155 mL/min/100 g, n = 159, P = 0.018) showed significantly poorer 1-year graft survival compared with the intermediate-PF group (PF ≥ 65 mL/min/100 g and < 155 mL/min/100 g, n = 632). The patients in the low-PF group had severe reperfusion injury and were more frequently complicated with primary nonfunction (P = 0.013) and early allograft dysfunction (P < 0.001) compared with the other groups. In contrast, the patients in the high-PF group had milder reperfusion injury, but had lower intraoperative hepatic artery flow with higher incidence of hepatic artery thrombosis (P = 0.043) and biliary complication (P = 0.041) compared with the other groups. CONCLUSIONS These results suggest that intraoperative PF plays an important role in determining early graft outcomes after DDLT.

The primary aim of this single-center, phase 1 exploratory study was to investigate the safety, feasibility, and impact on intrahepatic hemodynamics of a fresh frozen plasma (FFP)-based perfusate in ex situ liver normothermic machine perfusion (NMP) preservation. Using an institutionally developed perfusion device, 21 livers (13 donations after brain death and 8 donations after circulatory death) were perfused for 3 hours 21 minutes to 7 hours 52 minutes and successfully transplanted. Outcomes were compared in a 1:4 ratio to historical control patients matched according to donor and recipient characteristics and preservation time. Perfused livers presented a very low resistance state with high flow during ex situ perfusion (arterial and portal flows 340 ± 150 and 890 ± 70 mL/minute/kg liver, respectively). This hemodynamic state was maintained even after reperfusion as demonstrated by higher arterial flow observed in the NMP group compared with control patients (220 ± 120 versus 160 ± 80 mL/minute/kg liver, P = 0.03). The early allograft dysfunction (EAD) rate, peak alanine aminotransferase (ALT), and peak aspartate aminotransferase (AST) levels within 7 days after transplantation were lower in the NMP group compared with the control patients (EAD 19% versus 46%, P = 0.02; peak ALT 363 ± 318 versus 1021 ± 999 U/L, P = 0.001; peak AST 1357 ± 1492 versus 2615 ± 2541 U/L, P = 0.001 of the NMP and control groups, respectively). No patient developed ischemic type biliary stricture. One patient died, and all other patients are alive and well at a follow-up of 12-35 months. No device-related adverse events were recorded. In conclusion, with this study, we showed that ex situ NMP of human livers can be performed safely and effectively using a noncommercial device and an FFP-based preservation solution. Future studies should further investigate the impact of an FFP-based perfusion solution on liver hemodynamics during ex situ normothermic machine preservation.

This study estimated the utility of technical variant grafts (TVGs), such as split/reduced liver transplantation (SRLT) and living donor liver transplantation (LDLT), in pediatric acute liver failure (PALF). PALF is a devastating condition portending a poor prognosis without liver transplantation (LT). Pediatric candidates have fewer suitable deceased donor liver transplantation (DDLT) donor organs, and the efficacy of TVG in this setting remains incompletely investigated. PALF patients from 1995 to 2015 (age18 years) were identified using the Scientific Registry of Transplant Recipients (n = 2419). Cox proportional hazards model and Kaplan-Meier curves were used to assess outcomes. Although wait-list mortality decreased (19.1% to 9.7%) and successful transplantations increased (53.7% to 62.2%), patients1 year of age had persistently higher wait-list mortality rates (20%) compared with other age groups (P 0.001). TVGs accounted for only 25.7% of LT for PALF. In the adjusted model for wait-list mortality, among other factors, increased age (subhazard ratio [SHR], 0.97 per year; P = 0.020) and access to TVG were associated with decreased risk (SHR, 0.37; P 0.0001). LDLT recipients had shorter median waiting times compared with DDLT (LDLT versus DDLT versus SRLT, 3 versus 4 versus 5 days, respectively; P = 0.017). In the adjusted model for post-LT survival, LDLT was superior to DDLT using whole grafts (SHR, 0.41; P = 0.004). However, patient survival after SRLT was not statistically different from DDLT (SHR, 0.75; P = 0.165). In conclusion, despite clear advantages to reduce wait-list mortality, TVGs have been underutilized in PALF. Early access to TVG, especially from LDLT, should be sought to further improve outcomes.

Purpose of review Neuroendocrine tumor (NET) metastasis localized to the liver is an accepted indication for liver transplantation as such tumors have a low biological aggressiveness in terms of malignancy and are slow growing. Recent findings The long-term results are comparable with and in some cases even better than those of transplantations performed for primary liver cancer. However, compared with nonmalignant conditions, neuroendocrine liver metastasis (NELM) may result in an inferior outcome of transplantation. In the face of the scarcity of donated organs and recent improved results of non-surgical treatment for NELM, controversy over patient selection and timing for liver transplantation continues. Summary In this review, we provide an overview of the diagnostic work-up and selection criteria of patients with NELM being considered for liver transplantation. Thereafter, we provide a critical analysis of the reported outcomes of OLT.

Background Uterine transplantation is a novel treatment for uterine factor infertility (UFI), a condition which affects women who have an absent or nonfunctioning uterus and cannot carry their own biological children. Traditionally, surrogacy and adoption have been the only options for women with UFI. With recent successful living donor transplants in a clinical trial from Sweden, there is new hope for women with UFI to be able to experience pregnancy.

Objective: To review the use of rabbit antithymocyte globulin (rATG) induction therapy in liver transplant recipients. Data Sources: A MEDLINE literature search (inception to March 2016) was conducted using the search terms rabbit antithymocyte globulin, liver transplantation, and induction. References from extracted sources were further searched for any relevant, missed data sources. Study Selection and Data Extraction: All English-language randomized and observational studies were included. Data Synthesis: A total of 9 studies were included in this review evaluating rATG’s use for induction therapy. All studies were single-center analyses. rATG induction is utilized to delay calcineurin inhibitor initiation and to minimize or avoid steroids. Patients receiving rATG induction tended to have improved renal function compared with patients not receiving induction. Overall, rejection rates tended to be lower in recipients administered rATG. Regimens varied in each study, with most recipients receiving 2 to 3 doses of induction therapy. Conclusions: rATG induction therapy may lead to improved renal function and lower rejection rates following liver transplant. The use of this medication can help avoid unwanted adverse effects from other immunosuppression agents. Because of the potential benefits with this induction agent, rATG may have a larger role in induction therapy for liver transplant recipients.

Background The aim of this study was to assess the effect of low-dose adenosine on hepatic artery flow (HAF) when administered intraoperatively by continuous infusion. Materials and Methods Between January 2009 and August 2009, 74 patients underwent orthotopic liver transplantation (OLT). Ten patients were enrolled for adenosine treatment, and 64 non-study patients served as controls. After arterial reperfusion, a 16-G central venous catheter was placed in the gastroduodenal artery, and adenosine was continuously infused at doses ranging from 0.7 to 2.8 μg/kg/min for 30 min. HAF and portal vein flow were measured using a transit time flow meter before adenosine infusion, during infusion, and 10 min after infusion. Liver function tests were monitored routinely, duplex ultrasonography was performed on postoperative day 1, and the hepatic artery resistive index measured. The patients were followed for 1 year. Results Adenosine significantly increased HAF at doses from 0.7 to 2.8 μg/kg/min. The smallest increase in HAF was 24% above the baseline; in 80% of patients, the increase in HAF was >50% of the baseline values. In 2 patients, HAF was increased by >300%. The dosing started at 0.7 μg/kg/min, and 6 of 10 patients responded. Three patients required an increase to 1.4 μg/kg/min. Doses >2.8 μg/kg/min did not further increase HAF. One patient showed a minimal response regardless of the dose. There were no differences between the adenosine group and control group with respect to liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and International Normalized Ratio), platelet count on POD2, hepatic artery resistive index, and post-transplant length of stay, intensive care days, or 1-year patient survival rates. Conclusions This pilot study established that adenosine administered directly into the hepatic artery produces a similar effect on HAF in cadaveric liver transplant recipients to that found in the laboratory without producing systemic side effects.

The hepatic venous pressure gradient (HVPG) measurement is known to correlate with the severity of portal hypertension in patients with liver cirrhosis. This retrospective study investigated the clinical value of preoperative measurement of HVPG in patients who underwent adult-to-adult living donor liver transplantation (LDLT) and its predictive value for hepatic hemodynamics after graft reperfusion. For this study, 75 patients who underwent adult-to-adult LDLT were divided into 2 groups (HVPG

Portal vein thrombosis (PVT) is commonly encountered during liver transplantation (LT). Depending on the grade of thrombosis, varied management strategies are indicated. The aims of this study are to clarify the contemporary role of renoportal anastomosis (RPA) in patients with splanchnic vein thrombosis (SVT) undergoing LT and to systematically analyze all reported cases of RPA. A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta- Analyses statement guidelines. The study was limited to studies reported in English between January 1997 and May 2017. Only retrospective single center studies were included in the analysis. A total of 66 patients with SVT were reported to have undergone RPA during LT. Transient renal dysfunction was reported in 12 patients (18.1%), variceal hemorrhage in 2 patients (3%), early portal vein (PV) re-thrombosis in 2 patients (3%), chronic renal dysfunction in 2 patients (3%), and late PV re-thrombosis in 1 patient (1.5%). The overall patient and graft survival were each 80%. This analysis illustrates the decades-long evolution of a technique practiced across the field of transplantation. Postoperative complications and graft survival appear to be encouraging, even in the setting of SVT.

Background Higher rates of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in patients with chronic hepatitis B virus (HBV) infection have been reported. This can influence their selection for LT and post-LT monitoring. Objective The aim of this work was to compare the rates of post-LT HCC recurrence and survival in HBV and non-HBV patients with the use of the United Network for Organ Sharing (UNOS) database. Methods After accessing the UNOS database, we analyzed patients with HCC stage T2 who underwent LT from cadaveric donors on or after August 24, 1998. Propensity score matching based on age, Model for End-Stage Liver Disease (MELD), and donor risk index was used to match HBV-HCC patients to HCC patients with other underlying liver diseases: hepatitis C virus (HCV), alcoholic liver disease (ALD), both HCV + ALD, and nonalcoholic steatohepatitis (NASH). Kaplan-Meier plots and multivariable analysis (with the use of propensity score, age, sex, and race) were used to assess post-LT HCC recurrence and overall survival. Results A total of 4,480 HCC patients were matched. Their average age was 57 ± 7.8 years and average calculated MELD score was 13. Within 5 years of LT, 5.5% of patients had HCC recurrence and 20% died. HBV-HCC patients had 1.9 and 1.8 times higher hazard of tumor recurrence compared with ALD and NASH patients, respectively, and a 32% lower hazard of death than patients with HCV + ALD. There was no evidence of any other significant difference in HCC recurrence or survival among the etiology groups. Conclusions HCC recurrence and survival rates following LT for HCC patients with chronic HBV infection are similar to those of HCC patients with other underlying liver diseases. These findings support LT as a viable option for HCC-HBV patients.

Severe portal hyperperfusion (PHP) after liver transplantation has been shown to cause intrahepatic arterial vasoconstriction secondary to increased adenosine washout (hepatic artery buffer response). Clinically, posttransplant PHP can cause severe cases of refractory ascites and hydrothorax. In the past, we reported our preliminary experience with the use of splenic artery embolization (SAE) as a way to reduce PHP. Here we present our 5-year experience with SAE in orthotopic liver transplantation (OLT). Between January 2007 and December 2011, 681 patients underwent OLT at our institution, and 54 of these patients underwent SAE for increased hepatic arterial resistance and PHP (n=42) or refractory ascites/hepatic hydrothorax (n=12). Patients undergoing SAE were compared to a control group matched by year of embolization, calculated Model for End-Stage Liver Disease score, and liver weight. SAE resulted in improvements in hepatic artery resistive indices (0.92±0.14 and 0.76±0.10 before and after SAE, respectively; P

Introduction De novo autoimmune hepatitis, also known as plasma cell hepatitis, is an increasingly recognized entity following liver transplantation. The aim of this study is to investigate the long-term outcomes of patients with de novo autoimmune hepatitis. Methods Using transplant liver biopsy database, we identified all patients showing plasma cell hepatitis following liver transplantation between 2008 and 2013. The diagnosis of plasma cell hepatitis was based on the histologic features from liver biopsies. Results A total of 30 patients with plasma cell hepatitis were identified. Underling liver disease were hepatitis C virus (n = 11) and non–hepatitis C virus-related disease (n = 19). The interval period from liver transplantation to development of plasma cell hepatitis was 20 (2–246) months during 6 (1.5–25.8) years after liver transplantation. The mean international autoimmune hepatitis score and frequency of acute cellular rejection episode prior to the diagnosis of plasma cell hepatitis were lower in the patients with hepatitis C virus than those underlying non–hepatitis C virus-related disease. Twenty-seven patients (90.0%) showed complete biochemical response to plasma cell hepatitis treatment, but 10 (37.0%) patients relapsed. During the median 72 months' follow-up after liver transplantation, 9 (30.0%) patients progressed to cirrhosis (median 37 months) and 10 (33.3%) patients died or were retransplanted. Conclusions This long-term clinical observation shows that de novo autoimmune hepatitis represents one cause of graft loss in patients with or without hepatitis C virus. Although most patients exhibit a good response to medical therapy, de novo autoimmune hepatitis is likely to recur and progress to liver cirrhosis.

The MetS and cardiovascular disease are leading causes of late morbidity in adult liver transplantation recipients; however, limited data are available in pediatric liver transplantation. A single-center retrospective review was undertaken for patients who had a liver transplantation before 18 yr of age and were >5 yr post-transplantation, to study the prevalence of MetS, its components, and cardiac disorders. Fifty-eight patients were included in the study with a mean age at transplantation of 6.3 ± 6.1 yr and mean follow-up of 14.1 ± 6.0 yr. Of the study group, 41.4% were overweight or obese, with ongoing prednisone use and increased duration of follow-up being significant risk factors. Fifty-three patients had sufficient data for determining MetS, which was present in 17% of the patients. Although the prevalence of MetS is low in pediatric liver transplant recipients, it is associated with CKD and prednisone therapy (p

Under the “sickest first” Model for End-Stage Liver Disease (MELD) allocation, livers amenable to splitting are most often allocated to patients unsuitable for split liver transplantation (SLT). Our experience with SLT using hemilivers was reviewed. From April 2004 to June 2012, we used 25 lobar grafts (10 left lobes and 15 right lobes) for adult-sized recipients. Twelve recipients were transplanted with primary offers, and 13 were transplanted with leftover grafts. Six grafts were shared with other centers. The data were compared with matched whole liver grafts (n = 121). In 92% of donors, the livers were split in situ. Hemiliver recipients with severe portal hypertension had a greater graft-to-recipient weight ratio than those without severe portal hypertension (1.96% vs. 1.40%, p

Bacterial and fungal infections are major causes of morbidity and mortality after liver transplantation (LT). The role of intestinal decontamination in the prevention of post-LT infections is controversial. Rifaximin is widely used for the treatment of hepatic encephalopathy. The effect of rifaximin on post-LT infections is unknown. The aim of our study was to determine the effect of rifaximin therapy in the pretransplant period on early bacterial infections (EBIs) and fungal infections within the first 30 days after LT. All adult patients who underwent LT at our institution (January 2009 to July 2011) were included in this retrospective cohort study. Patients receiving antibiotics other than pretransplant protocol antibiotics were excluded. Patients were stratified into 2 groups based on the presence or absence of rifaximin therapy for at least 2 days before LT. Infections were defined by the isolation of any bacterial or fungal organisms within 30 days of LT. Multivariate regression analysis, Student t tests, and Pearson's chi-square tests were used to compare the 2 groups. Two hundred sixty-eight patients were included, and 71 of these patients (26.5%) were on rifaximin at the time of LT. The 2 groups were comparable with respect to age, sex, race, and Model for End-Stage Liver Disease score. There were no significant differences in the rates of EBIs (30% for the non-rifaximin group and 25% for the rifaximin group, P = 0.48) or fungal infections between the 2 groups. There was no increase in antimicrobial resistance among the infecting organisms. There was no difference in survival between the rifaximin and non-rifaximin groups (98% versus 97%, P = 0.36). In conclusion, the use of rifaximin in the pre-LT period was not associated with an increased risk of bacterial or fungal infections in the early post-LT period. Liver Transpl 20:544–551, 2014. © 2014 AASLD.

Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis characterized by fibrosis and calcification of the intestine that, in severe cases, can progress to intestinal failure and total parenteral nutrition dependency. Medical and surgical interventions carry a poor prognosis in these patients. We describe a case of a 36-year-old female with end-stage kidney disease and severe EPS not amenable to surgical intervention who underwent a combined intestinal and kidney transplantation. At 3 years posttransplantation, the patient has normal intestinal and kidney function. This represents, to our knowledge, the first report of severe EPS and end-stage kidney disease treated with a combined transplant.

The growing demand for liver transplantation and the concomitant scarcity of cadaveric livers have increased the need for living donor liver transplantation (LDLT). Ensuring the safety of donors and recipients is critical. The preoperative identification of the vascular and biliary tract anatomy with 3-dimensional (3D) printing may allow better preoperative surgical planning, avert unnecessary surgery in patients with potentially unsuitable anatomy, and thereby decrease the complications of liver transplant surgery. We developed a protocol and successfully 3D-printed synthetic livers (along with their complex networks of vascular and biliary structures) replicating the native livers of 6 patients: 3 living donors and 3 respective recipients who underwent LDLT. To our knowledge, these are the first complete 3D-printed livers. Using standardized preoperative, intraoperative, and postoperative assessments, we demonstrated identical anatomical and geometrical landmarks in the 3D-printed models and native livers.

Hepatitis C virus (HCV) infection is the leading cause of liver disease in hemophilia patients. In those with human immunodeficiency virus (HIV)/HCV coinfection, the rate of liver disease progression is greater than in HCV monoinfected individuals. Despite antiretroviral therapy, which slows HCV liver disease progression, some require transplantation. Whether transplant outcomes are worse in hemophilic (H) rather than nonhemophilic (NH) candidates is unknown. In order to determine rates and predictors of pretransplant and posttransplant survival, we conducted a retrospective observational study using United Network for Organ Sharing national transplant registry data, comparing HCV+ H and NH candidates. We identified 2502 HCV+ liver transplant candidates from 8 US university-based transplant centers, between January 1, 2004 to December 31, 2010, including 144 HIV+ (6%) and 2358 HIV–; 36 H (1%) and 2466 NH; 1213 (48%) transplanted and 1289 not transplanted. Other than male predominance and younger age, each were P

Objective To share our experience in performing the first-ever deceased-donor uterine transplant in the United States. Design This video uses an animation and footage from a uterine transplantation procedure to review the steps and techniques involved in performing a uterine transplant. Setting Academic, multisite medical center. Patient(s) A reproductive-age patient with Mayer-Rokitansky-Kuster-Hauser syndrome. Intervention(s) Transplantation of a viable uterus from a deceased donor. Main Outcome Measure(s) Assessment of posttransplantation uterine graft viability. Result(s) This video article describes the essential steps in the uterine transplant process, including selecting an appropriate donor with no history of infertility or uterine malformations. Furthermore, a deceased donor should exhibit brain death but not cardiac death. We also review our inclusion criteria for suitable recipients. In this video we outline the key steps in a uterine transplantation procedure and demonstrate footage from an actual transplant procedure. These steps include establishing bilateral end-to-side vascular anastomoses between the donor uterine artery and vein and the recipient's external iliac vessels. Once this has been completed and reperfusion noted of the donor uterus, connection to the recipient vaginal cuff is then performed. Conclusion(s) Uterine transplantation, although currently experimental, has gained the potential to become the first true treatment for uterine factor infertility. This procedure can become a promising option for the approximately 1.5 million women worldwide for whom pregnancy is not possible because of the absence of the uterus or presence of a nonfunctional uterus. Deceased donor uterine transplantation will further serve to broaden accessibility for this procedure.

Background Current recommended regimens to treat patients with hepatitis C virus (HCV) infection after liver transplantation include the use of ribavirin (RBV). Limited data are available on the efficacy of RBV-free regimens posttransplant, particularly the use of sofosbuvir (SOF)/ledipasvir (LDV) without RBV in this patient population. We aimed to assess the efficacy and safety of SOF/LDV fixed-dose combination without RBV in patients with HCV recurrence posttransplant. Methods This is a retrospective study of 46 patients with HCV recurrence posttransplant. SOF/LDV without RBV was used for 12 weeks in patients with early-stage fibrosis (F0-F2) or for 24 weeks in those with advanced fibrosis (F3-F4) and/or cholestatic hepatitis. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment. Secondary outcomes included relapse after treatment and adverse events. Results Forty-six patients, with a mean age of 62 ± 8 years, a median duration since time of transplant of 904 days (range, 78-3525 days), an HCV genotype 1, and a mean baseline viral load of 7.79 million IU/mL, were treated. Of these, 32 patients were treated for 12 weeks, and 14 patients were treated for 24 weeks. Twenty-five patients (54%) were treatment experienced (21 with interferon and 4 with SOF). All 46 patients (100%) achieved sustained virological response (SVR) 12. Neither virologic relapses nor serious adverse events were noted. Conclusions The combination of SOF/LDV without RBV for 12 or 24 weeks produced 100% SVR 12 in patients with HCV recurrence after liver transplantation. The use of RBV may not be necessary to achieve SVR in this patient population.

Donation after circulatory death (DCD)donors show heterogeneous hemodynamic trajectories following withdrawal of life support. Impact of hemodynamics in DCD liver transplant isunclear and objective measures of graft viability would ease transplant surgeon decision making and inform safe expansion of the donor organ pool. This retrospective study tested whether hemodynamic trajectories associated withtransplant outcomes in DCD liver transplantation (n = 87). Using longitudinal clustering statistical techniques we phenotyped DCD donors based on hemodynamic trajectory for both mean arterial pressure (MAP) and peripheral oxygen saturation (SpO2) following withdrawal of life support. Donors were categorized into 3 clusters: those who gradually decline after withdrawal of life support (cluster 1), those who maintain stable hemodynamics followed by rapid decline (cluster 2), and those who decline rapidly (cluster 3). Clustering outputs were used to compare characteristics and transplant outcomes. Cox proportional hazards modeling revealed hepatocellular carcinoma (HR = 2.53, P = 0.047), cold ischemia time (HR = 1.50 per hour, P = 0.027), and MAP cluster 1 were associated with increased risk of graft loss (HR =3.13, P = 0.021), but not SpO2 cluster (P = 0.172) or donor warm ischemia time (DWIT) (P = 0.154). Despite longer DWIT, MAP and SpO2 clusters 2 showed similar graft survival to MAP and SpO2 clusters 3, respectively. Conclusion – Despite heterogeneity in hemodynamic trajectories, DCD donors can be categorized into 3 clinically meaningful subgroups that help predict graft prognosis. Further studies should confirm the utility of liver grafts from cluster 2. This article is protected by copyright. All rights reserved.

Nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of obesity and insulin resistance. The aim of this study was to determine the frequency of NASH as an indication for liver transplantation (LT) in children and young adults and to characterize patient and graft survival. The study included all children and young adult patients (up to the age of 40 years) who underwent LT in the United States for NASH cirrhosis from the 1987 to 2012 United Network for Organ Sharing (UNOS) database. Kaplan-Meier analysis was used to assess patient and graft survival. A total of 330 patients were included, 68% were Caucasian, and the mean BMI was 33.6 ± 6.3. Age at time of LT ranged between 4 and 40 years (mean 33.9 ± 6.6 years). Fourteen subjects were

Liver transplantation (LT) has been the preferred method for the treatment of patients with end-stage liver disease of variety of causes. Recurrence of the primary disease after liver transplantation is well known and is more common in certain etiologies of liver disease than others. Transplantation of liver for metabolic disorders not only replaces the diseased liver and corrects the metabolic defect, but also cures the disease permanently and potentially reverses the consequences and complications of the initial abnormalities depending on the severity of the complications, reversibility, and time interval between the diagnosis of the problem and replacement of the liver.

The aim of this study was to develop a tool for preoperatively predicting the need of a patient to attend an extended care facility after orthotopic liver transplantation (OLT). A multidisciplinary group, which included 2 transplant surgeons, 2 transplant nurses, 1 nurse manager, 2 physical therapists, 1 case manager, 1 home health care professional, 1 rehabilitation physician, and 1 statistician, met to identify preoperative factors relevant to discharge planning. The parameters that were examined as potential predictors of the discharge status were as follows: age, sex, language, Karnofsky score, OLT alone (versus a combined procedure), creatinine, bilirubin, international normalized ratio (INR), albumin, body mass index (BMI), Child-Turcotte-Pugh score, chemical Model for End-Stage Liver Disease score, renal dialysis, location before transplantation, comorbidities (encephalopathy, ascites, hydrothorax, and hepatopulmonary syndrome), diabetes mellitus (DM), cardiac ejection fraction and right ventricular systolic pressure, sex and availability of the primary caregiver, donor risk index, and donor characteristics. Between January 2004 and April 2010, 730 of 777 patients (94%) underwent only liver transplantation, and 47 patients (6%) underwent combined procedures. Five hundred nineteen patients (67%) were discharged home, 215 (28%) were discharged to a facility, and 43 (6%) died early after OLT. A multivariate logistic regression analysis identified the following parameters as significantly influencing the discharge status: a low Karnofsky score, an older age, female sex, an INR of 2.0, a creatinine level of 2.0 mg/dL, DM, a high bilirubin level, a low albumin level, a low or high BMI, and renal dialysis before OLT. The nomogram was prospectively validated with a population of 126 OLT recipients with a concordance index of 0.813. In conclusion, a new approach to improving the efficiency of hospital care is essential. We believe that this tool will aid in reducing lengths of stay and improving the experience of patients by facilitating early discharge planning. Liver Transpl, 2012. © 2012 AASLD.

As survival after orthotopic liver transplantation (OLT) improves, cardiovascular (CV) disease has emerged as the leading cause of non-graft-related deaths. The aims of our study were to determine the cumulative risk of CV events after OLT and to analyze predictive risk factors for those experiencing a CV event after OLT. We identified all adult patients who underwent OLT at our institution for end-stage liver disease between October 1996 and July 2008. The cumulative risk of CV events after OLT was analyzed with the Kaplan-Meier method. Multivariate logistic regression analysis was used to identify factors independently associated with CV events after OLT. In all, 775 patients were included in our study cohort (mean age of 53.3 years, female proportion = 44%, Caucasian proportion = 84%, median follow-up = 40 months). The most common indications for OLT were hepatitis C virus (33.2%), alcohol (14.5%), and cryptogenic cirrhosis (12.7%). Eighty-three patients suffered 1 or more CV events after OLT. Posttransplant metabolic syndrome was more prevalent in patients with CV events versus patients with no CV events (61.4% versus 34.1%, P < 0.001). According to a multivariate analysis, independent predictors of CV events were an older age at transplantation [odds ratio (OR) = 1.2, addition of 95% confidence interval (CI) = 1.1-1.3, P = 0.006], male sex (OR = 2.0, 95% CI = 1.2-3.3, P = 0.01), posttransplant diabetes (OR = 2.0, 95% CI = 1.3-3.3, P = 0.003), posttransplant hypertension (OR = 1.8, 95% CI = 1.1-3.0, P = 0.02), and mycophenolate mofetil (OR = 2.0, 95% CI = 1.3-3.2, P = 0.003). Among post-OLT patients, the cumulative risk at 5 years of 13.5%, respectively. In conclusion, cardiac complications after liver transplantation are common (Approximately 10% of patients experience 1 or move cv events). Patients with posttransplant hypertension and diabetes, which are modifiable risk factors, are approximately twice as likely to experience a CV event.

Severe ischemia/reperfusion (IR) injury is associated with poor hepatic microperfusion. The aim of this study was to investigate the role of hepatic artery flow (HAF) and portal vein flow (PVF) in IR injury. From January 2004 to June 2008, 566 patients underwent orthotopic liver transplantation (OLT). The data were retrospectively reviewed via the transplant database. Patients with hepatic artery (HA) or portal vein (PV) thrombosis and retransplant patients were excluded. Intraoperative PVF and HAF values and graft weights were measured routinely, and the central venous pressure, mean arterial pressure, cardiac output, and cardiac index were recorded with hepatic blood flow measurements. Complete data were available for 312 primary OLT recipients (215 males and 97 females; mean age = 54 ± 10 years). The patients' follow-up ranged from 215 to 1746 days (705 ± 408 days). IR injury was defined by the aspartate aminotransferase (AST) level on postoperative day (POD) 2, and the patients were divided into 3 groups: (1) mild IR injury [AST 1000 U/L; n = 67 (21%)]. The demographics and pre-OLT variables (the Model for End-Stage Liver Disease score (MELD), platelet counts, PV thrombosis, transjugular intrahepatic portosystemic shunts, and shunts on computed tomography scans) were similar in all groups. The graft survival rate was 99% in group 1, 95.2% in group 2 (P = 0.02), and 92.3% in group 3 (P = 0.016). The patient survival rates were similar in the 3 groups. The cold ischemia time (CIT) was significantly higher in group 3 versus group 1 (P < 0.007). In the statistical analysis, low HAF, PVF, total liver blood flow (TLBF), and augmented HAF values were associated with a greater likelihood of elevated AST levels on POD 2. The strongest univariate predictors of AST were reduced augmented HAF (mL/minute/100 g) values (P < 0.001) and reduced TLBF (mL/minute/100 g) values (P < 0.001). In a covariate analysis with adjustments for CIT and donor variables, the blood flow parameters remained important predictors of graft function. In conclusion, this report demonstrates for the first time that reduced hepatic blood flow is a significant finding in patients with severe hepatic IR injury.

Key Points 1. Our increasing understanding of signaling pathways and cellular interactions in transplant immunobiology and the availability of novel immunosuppressive agents have facilitated targeted strategies. 2. The driving forces behind the development of new immunosuppressive regimens are the long-term complications of current immunosuppressive regimens (particularly renal dysfunction and metabolic disturbances). 3. By regulatory mandate, the requirement for the primary endpoint to be a composite of death, graft loss, and rejection remains intact; however, current and future clinical trials could incorporate key secondary endpoints that address renal and metabolic derangements. Liver Transpl, 2011. © 2011 AASLD.

Background. A pretransplant positive crossmatch in combined liver kidney transplants (CLK) is not considered a contraindication based on the reported immunoprotection conferred by the liver allograft. However, antibody-mediated rejection of the kidney in CLK has been reported recently. This prompted our study to investigate the impact of presensitization on CLK recipient outcomes. Methods. We examined kidney allograft and patient survival by indication of sensitization using Scientific Registry of Transplant Recipients data on CLK performed from 1995 to 2008. We defined sensitization as panel reactive antibody (PRA) more than 10% or a positive T-cell crossmatch (TXM). Results. Among 2484 CLK recipients with available PRA or TXM information, 30% had positive TXM or PRA more than 10%. Among those with TXM information, 12% had a positive crossmatch (n=234). In univariate analyses, patient (P=0.002) and overall kidney graft survival (P=0.015) were significantly diminished among sensitized patients. Differences in patient survival translated to estimated half-lives of 10.3 years among nonsensitized recipients versus 7.8 years among sensitized recipients, In multivariable Cox models, allosensitization was independently associated with patient death (adjusted hazard ratio=1.22, 95% CI, 1.04–1.43) and overall kidney graft loss (adjusted hazard ratio=1.16, 95% CI, 1.00–1.36). Conclusions. These results suggest a negative impact of presensitization on patient and overall renal allograft survival in CLK. Accordingly, presensitization may need to be considered in risk stratification and clinical management of CLK.

Refractory ascites (RA) is a challenging complication after orthotopic liver transplantation. Its treatment consists of the removal of the precipitating factors. When the etiology is unknown, supportive treatment can be attempted. In severe cases, transjugular intrahepatic portosystemic shunts, portocaval shunts, and liver retransplantation have been used with marginal results. Recently, splenic artery embolization (SAE) has been described as an effective procedure for reducing portal hyperperfusion in patients undergoing partial or whole liver transplantation. Here we describe our experience with SAE for the treatment of RA. Between June 2004 and June 2010, 6 patients underwent proximal SAE for RA. Intraoperative flow measurements, graft characteristics, embolization portal vein (PV) velocities before and after SAE, and spleen/liver volume ratios were collected and analyzed. The response to treatment was assessed with imaging (ultrasound/computed tomography) and on the basis of clinical outcomes (weight changes, diuretic requirements, and the time to ascites resolution). The PV velocity decreased significantly for each patient after the embolization (median = 66.5 cm/second before SAE and median = 27.5 cm/second after SAE, P < 0.01). All patients experienced a significant postprocedural weight loss (mean = 88.1 ± 28.4 kg before SAE and mean = 75.8 ± 28.4 kg after SAE, P < 0.01) and a dramatic decrease in their diuretic requirements. All but 1 of the patients experienced a complete resolution of ascites after a median time of 49.5 days (range = 12-295 days). No patient presented with postembolization complications. In conclusion, SAE was effective in reducing the PV velocity immediately after the procedure. Clinically, this translated into a dramatic weight loss, a reduction of diuretic use, and a resolution of ascites. SAE appears to be a safe and effective treatment for RA.