A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation.

BACKGROUND & AIMS: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values. METHODS: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. RESULTS: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups and to provide a valid comparator cohort for future clinical trials. LAY SUMMARY: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2,219 liver transplantations following controlled DCD donation in 17 centres worldwide. Donor and recipient combinations with higher risk had significantly worse outcomes. However, the use of novel organ perfusion technology helped high-risk patients achieve similar outcomes as the benchmark cohort.

Early United States experience with liver donation after circulatory determination of death using thoraco-abdominal normothermic regional perfusion: A multi-institutional observational study.

Mortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality. We retrospectively reviewed outcomes of the first 13 livers transplanted from TA-NRP donors in the US. Nine centers transplanted livers from eight organ procurement organizations. Median donor age was 25 years; median agonal phase was 13 minutes. Median recipient age was 60 years; median lab MELD score was 21. Three patients (23%) met early allograft dysfunction (EAD) criteria. Three received simultaneous liver-kidney transplants; neither had EAD nor delayed renal allograft function. One recipient died 186 days post-transplant from sepsis but had normal presepsis liver function. One patient developed a biliary anastomotic stricture, managed endoscopically; no recipient developed clinical evidence of ischemic cholangiopathy (IC). Twelve of 13 (92%) patients are alive with good liver function at 439 days median follow-up; one patient has extrahepatic recurrent HCC. TA-NRP DCD livers in these recipients all functioned well, particularly with respect to IC, and provide a valuable option to decrease deaths on the waiting list.

Hepatitis C-associated focal proliferative glomerulonephritis in an aviremic recipient of a hepatitis C-positive antibody donor liver.

Shortage of organs for liver transplantation (LT) and the availability of highly efficient pan-genotypic direct-acting antivirals (DAAs) against hepatitis C virus (HCV) have allowed the use of livers from HCV-positive antibody/negative nucleic acid test donors (dHCV Ab+/NAT-) into aviremic HCV recipients over the last few years. We report the case of a patient who received an LT from an HCV Ab+/NAT- donor and, after HCV viremic conversion, developed a nephrotic syndrome due to a focal proliferative glomerulonephritis early after LT. Patient's renal function and proteinuria resolved after successful treatment with DAAs. Renal and hepatic function remain normal over 24 months of follow-up. This case restates the success of LT using livers from dHCV Ab+/NAT- in aviremic recipients in the context of DAAs while illustrating the risk for potential complications associated with the HCV transmission and reinforcing the importance of early initiation of anti-HCV therapy.

Liver Transplantation Using Hepatitis C Virus-Viremic Donors Into Hepatitis C Virus-Aviremic Recipients as Standard of Care.

Liver transplantation (LT) using allografts from hepatitis C virus (HCV)-viremic/nucleic acid testing-positive donors' (DNAT+) organs into HCV-aviremic recipients (rHCV-) has been limited owing to nearly universal HCV transmission and concerns regarding availability, safety, and efficacy post-LT with direct-acting antiviral (DAA) therapy. We report our experience of LT using DNAT+ organs into rHCV- as a routine standard of care. Following verification of DAA access, absence of critical drug-drug interactions (DDIs) with DAAs, and informed consent, allocated DNAT+ organs were offered to patients on the waiting list for LT irrespective of recipient HCV status. Between June 2018 and December 2019, 292/339 rHCV- received an LT. Forty-seven patients were excluded from analysis because of recipient HCV viremia, refusal to receive DNAT+ organs, or inability to receive DAA therapy post-LT. Of these 292 patients, 61 rHCV- received DNAT+ livers (study group), and 231 rHCV- received DNAT- (aviremic donors [nuclear acid test-negative donors]) livers (control group). Recipient and donor characteristics as well as 1-year post-LT patient and graft survival were similar between groups. In the study group, 4 patients died, and 1 patient required retransplantation within the first year post-LT (all unrelated to HCV); 56 patients received DAA therapy, with a median time from LT to the start of DAA treatment of 66.9 days (interquartile range [IQR], 36-68.5), and 51 patients completed DAA treatment, all achieving sustained virologic response for 12 or more weeks (SVR-12) (1 patient required retreatment owing to relapse following initial DAA therapy). No patients had evidence of fibrosing cholestatic hepatitis or extrahepatic manifestations of HCV. This report indicates that transplantation of DNAT+ livers into rHCV- and subsequent DAA therapy is associated with clinical outcomes comparable to those achieved with DNAT- allografts.

Assessment of Response to Transcatheter Arterial Chemoembolization with Doxorubicin-eluting Microspheres: Tumor Biology and Hepatocellular Carcinoma Recurrence in a 5-year Transplant Cohort.

Purpose To assess response to transcatheter arterial chemoembolization (TACE) based on immune markers and tumor biology in patients with hepatocellular carcinoma (HCC) who were bridged to liver transplantation, and to produce an optimized pretransplantation model for posttransplantation recurrence risk. Materials and Methods In this institutional review board-approved HIPAA-compliant retrospective analysis, 93 consecutive patients (73 male, 20 female; mean age, 59.6 years; age range, 23-72 years) underwent TACE with doxorubicin-eluting microspheres (DEB) (hereafter, DEB-TACE) and subsequently underwent transplantation over a 5-year period from July 7, 2011, to May 16, 2016. DEB-TACE response was based on modified Response Evaluation Criteria in Solid Tumors. Imaging responses and posttransplantation recurrence were compared with demographics, liver function, basic immune markers, treatment dose, and tumor morphology. Treatment response and recurrence were analyzed with uni- and multivariate statistics, as well as internal validation and propensity score matching of factors known to affect recurrence to assess independent effects of DEB-TACE response on recurrence. Results Low-grade tumors (grade 0, 1, or 2) demonstrated a favorable long-term treatment response in 87% of patients (complete response, 49%; partial response, 38%; stable disease [SD] or local disease progression [DP], 13%) versus 33% of high-grade tumors (grade 3 or 4) (complete response, 0%; partial response, 33%; SD or DP, 67%) (P < .001). Of the 93 patients who underwent treatment, 82 were followed-up after transplantation (mean duration, 757 days). Recurrence occurred in seven (9%) patients (mean time after transplantation, 635 days). Poor response to DEB-TACE (SD or DP) was present in 86% of cases and accounted for 35% of all patients with SD or DP (P < .001). By using only variables routinely available prior to liver transplantation, a validated model of posttransplantation recurrence risk was produced with a concordance statistic of 0.83. The validated model shows sensitivity of 83.6%, specificity of 82.6%, and negative predictive value of 98.4%, which are pessimistic estimates. Conclusion Response to DEB-TACE is correlated with tumor biology and patients at risk for posttransplantation recurrence, and it may be associated with HCC recurrence after liver transplantation. © RSNA, 2017 Online supplemental material is available for this article.

Outcomes utilizing imported liver grafts for recipients with hepatocellular carcinoma.

Liver transplantation (LT) offers the best chance of survival in selected patients with hepatocellular carcinoma (HCC). Wait-list mortality or dropout due to tumor progression can be significant, and therefore, timely transplantation is critical. Liver grafts discarded by outside organ procurement organizations are a potential source of grafts for low Model for End-Stage Liver Disease tumor patients. The primary aim of this study was to assess the disease-free and overall survival of patients with HCC transplanted with imported liver grafts (ILGs). Review of all patients transplanted for HCC between June 2005 and December 2014 was performed. Data on demographics, survival, and HCC recurrence were analyzed. During this time period, 59 out of 190 (31%) recipients with HCC received ILG. Of these 59 grafts, 54 were imported from within the region and 5 were from national offers (outside the region). The mean cold ischemia time for local liver grafts (LLGs) was 4.1 ± 1.5 hours versus 5.1 ± 1.4 hours for ILG (P < 0.001). The 1-, 3-, and 5-year patient survival was 90%, 85%, and 83% and 85%, 80%, and 79% for LLG and ILG (P = 0.08), respectively. The observed disease recurrence rate for both LLG and ILG recipients was equivalent. The median wait-list time for HCC recipients was 43 days (range, 2-1167 days). In conclusion, with careful graft assessment, the use of ILGs results in comparable outcomes following LT and no increased risk of HCC recurrence. Use of ILGs maximizes the donor pool and results in a higher rate of transplantation for HCC recipients. Liver Transplantation 23 299-304 2017 AASLD.

Predictive model and risk factors associated with a revised definition of early allograft dysfunction in liver transplant recipients.

INTRODUCTION: Early allograft dysfunction (EAD) is a well-defined clinical syndrome that reflects overall graft function within the first week after transplant. The aim of this study was to further refine the definition for EAD. METHOD: In this study, 1124 patients were included for analysis. Logistic regression was performed to identify markers of liver injury associated with 6-month patient and graft failure. RESULTS: Recursive partitioning identified cut-points for ALT/AST > 3000/6000 IU/dL observed within first week, with bilirubin ≥ 10 mg/dL and INR ≥ 1.6 on postoperative day 7 for the revised EAD model. The incidence of updated EAD was 15% (164/1124). Multivariable analysis identified eight risk factors associated with EAD: % macrosteatosis, donor location, donor weight, nonheart beating donors, type of organ transplanted, recipient-associated hepatocellular carcinoma, severity of postreperfusion syndrome, and the amount of transfused fresh frozen plasma. In the presence of EAD, the incidence of post-transplant renal replacement therapy and dialysis dependence increases. There was a significant association of the presence of EAD with 6-month mortality (12% vs 3%) and 6-month graft failure (8% vs 1%). CONCLUSION: Higher AST/ALT level needed as cutoff in comparison with the old EAD definition.

Thromboprophylaxis With Heparin During Orthotopic Liver Transplantation: Comparison of Hepcon HMS Plus and Anti-Xa Assays for Low-Range Heparin.

OBJECTIVES: The purpose of this study was to compare the agreement between two heparin assays, Hepcon HMS plus/Kaolin-ACT and Anti-Xa, and their predictive power in detecting circulating heparin levels post-reperfusion of the liver graft when compared with thromboelastogram (TEG) r time ratio in patients undergoing orthotopic liver transplantation (OLT). DESIGN: Prospective, observational cohort study design. SETTING: Single center, university hospital. PARTICIPANTS: Thirty-eight consecutive adults who had undergone liver transplant. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Paired arterial blood samples were collected before surgical incision, 5 minutes after administration of an average dose of 2,054±771 units of intravenous unfractionated heparin before caval cross-clamping, 5 minutes after portal reperfusion, 5 minutes after hepatic artery reperfusion, and 1 hour after hepatic artery reperfusion. The observations that heparin assay measurements were within the predetermined limits of agreement, strongly suggested the two heparin assays (Hepcon HMS plus and Anti-Xa assay) are interchangeable during prophylactic heparin dose therapy during OLT. Post-reperfusion, receiver operating characteristic curve analysis revealed high accuracy in measuring circulating heparin levels with both Anti-Xa and Hepcon HMS assays when compared with the TEG r time ratio assay. CONCLUSIONS: The point-of-care Hepcon HMS plus/Kaolin-ACT (activated clotting time) assay appeared to be a reliable alternative to the more expensive and laboratory-required Anti-Xa assay in monitoring the response to intravenous heparin in patients undergoing OLT.

Elevated Lung Shunt Fraction as a Prognostic Indicator for Disease Progression and Metastasis in Hepatocellular Carcinoma.

PURPOSE: To evaluate lung shunt fraction (LSF) as an early predictor for local disease progression or the development of metastatic disease. MATERIALS AND METHODS: Retrospective analysis was performed on 52 patients with hepatocellular carcinoma who underwent preradioembolization assessment, including the calculation of LSF. Comparison of preprocedural and postprocedural surveillance imaging was performed. Mean patient age was 67 years (range, 50-88 y), with a mean surveillance of 245 days (range, 24-871 d). Statistical analysis was conducted to assess the relationship between LSF and local disease progression or development of new metastatic disease. RESULTS: In patients in whom metastatic disease developed during routine surveillance, the mean LSF was almost double that in patients in whom no metastasis developed (18.3% vs 9.3%; P = .001). Patients with elevated LSFs were also more likely to show intrahepatic disease progression (15.6% vs 8.5%; P = .003). LSFs < 8% corresponded to negative predictive values of 74% for local disease progression and 95% for development of metastasis, signaling a better prognosis. Of pretreatment variables examined (age, sex, previous treatment with disease progression, lesion size, lesion number, LSF, α-fetoprotein level, and portal vein thrombus), only LSF was an independent predictor for new metastasis (odds ratio [OR] = 1.2; P = .01). LSF (OR = 1.2; P = .03) and progression after previous treatment (OR = 4.7; P = .04) were independent predictors for local progression. CONCLUSIONS: As local disease progression and metastatic disease were more likely to occur in patients with elevated LSFs, LSF may be the most sensitive predictor for local disease progression and new metastatic disease.

Epsilon-Aminocaproic Acid Has No Association With Thromboembolic Complications, Renal Failure, or Mortality After Liver Transplantation.

OBJECTIVES: To examine the role of epsilon-aminocaproic acid (EACA) administered after reperfusion of the donor liver in the incidences of thromboembolic events and acute kidney injury within 30 days after orthotopic liver transplantation. One-year survival rates between the EACA-treated and EACA-nontreated groups also were examined. DESIGN: Retrospective, observational, cohort study design. SETTING: Single-center, university hospital. PARTICIPANTS: The study included 708 adult liver transplantations performed from 2008 to 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: EACA administration was not associated with incidences of intracardiac thrombosis/pulmonary embolism (1.3%) or intraoperative death (0.6%). Logistic regression (n = 708) revealed 2 independent risk factors associated with myocardial ischemia (age and pre-transplant vasopressor use) and 8 risk factors associated with the need for post-transplant dialysis (age, female sex, redo orthotopic liver transplantation, preoperative sodium level, pre-transplant acute kidney injury or dialysis, platelet transfusion, and re-exploration within the first week after transplant); EACA was not identified as a risk factor for either outcome. One-year survival rates were similar between groups: 92% in EACA-treated group versus 93% in the EACA-nontreated group. CONCLUSIONS: The antifibrinolytic, EACA, was not associated with an increased incidence of thromboembolic complications or postoperative acute kidney injury, and it did not alter 1-year survival after liver transplantation.

Using on-site liver 3-D reconstruction and volumetric calculations in split liver transplantation.

BACKGROUND: Split liver transplantation increases the number of grafts available for transplantation. Pre-recovery assessment of liver graft volume is essential for selecting suitable recipients. The purpose of this study was to determine the ability and feasibility of constructing a 3-D model to aid in surgical planning and to predict graft weight prior to an in situ division of the donor liver. METHODS: Over 11 months, 3-D volumetric reconstruction of 4 deceased donors was performed using Pathfinder Scout© liver volumetric software. Demographic, laboratory, operative, perioperative and survival data for these patients along with donor demographic data were collected prospectively and analyzed retrospectively. RESULTS: The average predicted weight of the grafts from the adult donors obtained from an in situ split procedure were 1130 g (930-1458 g) for the extended right lobe donors and 312 g (222-396 g) for left lateral segment grafts. Actual adult graft weight was 92% of the predicted weight for both the extended right grafts and the left lateral segment grafts. The predicted and actual graft weights for the pediatric donors were 176 g and 210 g for the left lateral segment grafts and 308 g and 280 g for the extended right lobe grafts, respectively. All grafts were transplanted except for the right lobe from the pediatric donors due to the small graft weight. CONCLUSIONS: On-site volumetric assessment of donors provides useful information for the planning of an in situ split and for selection of recipients. This information may expand the donor pool to recipients previously felt to be unsuitable due to donor and/or recipient weight.

Thrombolytic protocol minimizes ischemic-type biliary complications in liver transplantation from donation after circulatory death donors.

Liver transplantation (LT) with donation after circulatory death (DCD) donors has been associated with a high rate of ischemic-type biliary strictures (ITBSs) and inferior graft survival. To investigate the impact of an intraoperative tissue plasminogen activator (tPA) on outcomes following DCD LT, we conducted a retrospective analysis of DCD LT at the Toronto General Hospital (TGH) and the Ochsner Medical Center (OMC). Between 2009 and 2013, 85 DCD LTs were performed with an intraoperative tPA injection (n = 30 at TGH, n = 55 at OMC), and they were compared with 33 DCD LTs without a tPA. Donor and recipient characteristics were similar in the 2 groups. There was no significant difference in the intraoperative packed red blood cell transfusion requirement (3.2 ± 3.4 versus 3.1 ± 2.3 U, P = 0.74). Overall, biliary strictures occurred less commonly in the tPA-treated group (16.5% versus 33.3%, P = 0.07) with a much lower rate of diffuse intrahepatic strictures (3.5% versus 21.2%, P = 0.005). After 1 and 3 years, the tPA group versus the non-tPA group had superior patient survival (97.6% versus 87.0% and 92.7% versus 79.7%, P = 0.016) and graft survival (96.4% versus 69.7% and 90.2% versus 63.6%, P < 0.001). In conclusion, a tPA injection into the hepatic artery during DCD LT reduces ITBSs and improves graft and patient survival without increasing the risk for bleeding.

US Liver Transplant Outcomes After Normothermic Regional Perfusion vs Standard Super Rapid Recovery.

Importance: Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR). Objective: To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery. Design, Setting, and Participants: This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers. Exposures: cDCD livers were recovered by either NRP or SRR. Main Outcomes and Measures: The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival. Results: A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts. Conclusion and Relevance: There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.

Liver transplantation in hepatitis B core-negative recipients using livers from hepatitis B core-positive donors: a 13-year experience.

The use of livers from hepatitis B surface antigen-negative (HBsAg- )/hepatitis B core antibody-positive (HBcAb+ ) donors in liver transplantation (LT) for HBsAg(-) /HBcAb- recipients is still controversial because of a lack of standard antiviral prophylaxis and long-term follow-up. We present our 13-year experience with the use of HBcAb+ donor livers in HBcAb- recipients. Patients received prophylaxis with hepatitis B immunoglobulin at the time of LT and then lamivudine daily. De novo hepatitis B virus (HBV) was defined as positive HBV DNA detection. Between January 1999 and December 2010, 1013 adult LT procedures were performed at our center. Sixty-four HBsAg- /HBcAb- patients (6.3%) received an HBsAg- /HBcAb+ liver. All donor sera were negative for HBcAb immunoglobulin M and HBV DNA. The mean follow-up was 48.8 ± 40.1 months (range = 1.2-148.8). Both the patient survival rates and the graft survival rates were 92.2% and 69.2% at 1 and 5 years, respectively. No graft losses or deaths were related to de novo HBV. Nine of the 64 patients (14.1%) developed de novo HBV. The mean time from LT to de novo HBV was 21.4 ± 26.1 months (range = 10.8-92.8 months). De novo HBV was successfully treated with adefovir or tenofovir. In conclusion, HBcAb+ allografts can be safely used in HBcAb- recipients without increased mortality or graft loss. Lifelong prophylaxis, continuous surveillance, and compliance are imperative for success. Should a de novo infection occur, our experience suggests that a variety of treatments can be employed to salvage the graft and obtain serum HBV DNA clearance.

Intraoperative Renal Replacement Therapy in Orthotopic Liver Transplantation.

Acute kidney injury in patients admitted to the hospital for liver transplantation is common, with up to 80% of pretransplant patients having some form of acute kidney injury. Many of these patients start on dialysis prior to their transplant and have it continued intraoperatively during their surgery. This review discusses the limited existing literature and expert opinion around the indications and outcomes around intraoperative dialysis (intraoperative renal replacement therapy) during liver transplantation. More specifically, we discuss which patients may benefit from intraoperative renal replacement therapy and the impact of hyponatremia and hyperammonemia on the dialysis prescription. Additionally, we discuss the complex interplay between anesthesia and intraoperative renal replacement therapy and how the need for clearance and ultrafiltration changes throughout the different phases of the transplant (preanhepatic, anhepatic, and postanhepatic). Lastly, this review will cover the limited data around patient outcomes following intraoperative renal replacement therapy during liver transplantation as well as the best evidence for when to stop dialysis.

Antibody-Mediated Rejection: A Review.

BACKGROUND: Chronic antibody injury is a serious threat to allograft outcomes and is therefore the center of active research. In the continuum of allograft rejection, the development of antibodies plays a critical role. In recent years, an increased recognition of molecular and histologic changes has provided a better understanding of antibody-mediated rejection (AMR), as well as potential therapeutic interventions. However, several pathways are still unknown, which accounts for the lack of efficacy of some of the currently available agents that are used to treat rejection. METHODS: We review the current diagnostic criteria for AMR; AMR paradigms; and desensitization, treatment, and prevention strategies. RESULTS: Chronic antibody-mediated endothelial injury results in transplant glomerulopathy, manifested as glomerular basement membrane duplication, double contouring, or splitting. Clinical manifestations of AMR include proteinuria and a rise in serum creatinine. Current strategies for the treatment of AMR include antibody depletion with plasmapheresis (PLEX), immunoadsorption (IA), immunomodulation with intravenous immunoglobulin (IVIG), and T cell- or B cell-depleting agents. Some treatment benefits have been found in using PLEX and IA, and some small nonrandomized trials have identified some benefits in using rituximab and the proteasome inhibitor-based therapy bortezomib. More recent histologic follow-ups of patients treated with bortezomib have not shown significant benefits in terms of allograft outcomes. Furthermore, no specific treatment approaches have been approved by the US Food and Drug Administration. Other agents used for more difficult rejections include bortezomib and eculizumab (an anti-C5 monoclonal antibody). CONCLUSION: AMR is a fascinating field with ample opportunities for research and progress in the future. Despite the use of advanced techniques for the detection of human leukocyte antigen (HLA) or non-HLA donor-specific antibodies, alloimmune response remains an important barrier for successful long-term allograft function. Treatment of AMR with currently available therapies has produced a variety of results, some of them suboptimal, precluding the development of standardized protocols. New therapies are promising, but randomized controlled trials are needed to find surrogate markers and improve the efficacy of therapy.

Novel Biliary Reconstruction Techniques During Liver Transplantation.

BACKGROUND: Biliary complications remain a significant problem following liver transplantation. Several surgical options can be used to deal with a significant size mismatch between the donor and recipient bile ducts during the biliary anastomosis. We compared biliary transposition to recipient biliary ductoplasty in cadaveric liver transplant. METHODS: A total of 33 reconstructions were performed from January 1, 2005 to December 31, 2013. In the biliary transposition group (n=23), 5 reconstructions were performed using an internal stent (5 or 8 French pediatric feeding tube), and 18 were performed without. Of the 10 biliary ductoplasties, 2 were performed with a stent. All patients were managed with standard immunosuppression and ursodiol. Follow-up ranged from 2 months to 5 years. RESULTS: No patients in the biliary transposition group required reoperation; 1 patient had an internal stent removed for recurrent unexplained leukocytosis, and 2 patients required endoscopic retrograde cholangiography and stent placement for evidence of stricture. Three anastomotic leaks occurred in the biliary ductoplasty group, and 2 patients in the biliary ductoplasty group required reoperation for biliary complications. CONCLUSION: Our results indicate that biliary reconstruction can be performed with either biliary transposition or biliary ductoplasty. These techniques are particularly useful when a significant mismatch in diameter exists between the donor and recipient bile ducts.

Balloon-Occlusion Technique for Managing Portal Vein Hemorrhage in Liver Transplantation.

BACKGROUND: Portal vein thrombosis (PVT) is relatively common among candidates for liver transplantation and can present significant intraoperative challenges. Depending on the extent of PVT, thromboendovenectomy (TEV), portal bypass, or systemic inflow may be required to restore portal inflow. While TEV is the most commonly used approach to restore anatomic portal inflow, portal vein injury and life-threatening hemorrhage are risks with this technique. CASE REPORT: We present a salvage technique for managing portal vein injury during TEV using intraluminal balloon occlusion of the portal vein during portal vein repair and reconstruction. This alternative mode of bleeding control optimizes exposure to the retropancreatic space and avoids direct application of vascular clamps that can cause further injury to the vessel and surrounding tissue. CONCLUSION: Careful preoperative planning and anticipation of potential problems are essential for safe and effective management of complex PVT intraoperatively. The balloon-occlusion technique can facilitate safe and efficient repair of a portal vein injury during TEV for liver transplantation.

Post-Liver Transplant Delirium Increases Mortality and Length of Stay.

BACKGROUND: Incidence of delirium after liver transplantation (LT) has been reported to occur in 10%-47% of patients and is associated with increased hospital and intensive care unit lengths of stay and poor outcomes. METHODS: Our primary objective was to evaluate the incidence and predisposing risk factors for developing delirium after LT. Our secondary objectives were to describe how delirium is managed in patients after LT, to examine the utilization of resources associated with delirium after LT, and to analyze the outcomes of patients who were treated for delirium after LT. RESULTS: In a population of 181 consecutive patients who received an LT, 38 (21.0%) developed delirium. In the multivariate analysis, delirium was associated with pretransplant use of antidepressants (odds ratio [OR] 3.34, 95% confidence interval [CI] 1.29-8.70) and pretransplant hospital admission for encephalopathy (OR 4.39, 95% CI 1.77-10.9). Patients with delirium spent more time on mechanical ventilation (2.0 vs 1.3 days, P=0.008) and had longer intensive care unit stays (4.6 vs 2.7 days, P=0.008), longer hospital stays (27.6 vs 11.2 days, P=0.003), and higher 6-month mortality (13.2% vs 1.4%, P=0.003) than patients who did not develop delirium. CONCLUSION: The presence of delirium is common after LT and is associated with high morbidity and mortality within the first 6 months posttransplant. Pretransplant factors independently associated with developing delirium after LT include prior use of antidepressants and pretransplant hospital admission for encephalopathy. Efforts should be made to identify patients at risk for delirium, as protocol-based management may improve outcomes in a cost-effective manner.