Emamaullee, Juliet

Patients with cirrhosis have abnormal coagulation indices such as a high international normalized ratio and low platelet count, but these do not correlate well with periprocedural bleeding risk. We sought to develop a consensus among the multiple stakeholders in cirrhosis care to inform process measures that can help improve the quality of the periprocedural management of coagulopathy in cirrhosis. We identified candidate process measures for periprocedural coagulopathy management in multiple contexts relating to the performance of paracentesis and upper endoscopy. An 11-member panel with content expertise was convened. It included nominees from professional societies for interventional radiology, transfusion medicine, and anesthesia as well as representatives from hematology, emergency medicine, transplant surgery, and community practice. Each measure was evaluated for agreement using a modified Delphi approach (3 rounds of rating) to define the final set of measures. Out of 286 possible measures, 33 measures made the final set. International normalized ratio testing was not required for diagnostic or therapeutic paracentesis as well as diagnostic endoscopy. Plasma transfusion should be avoided for all paracenteses and diagnostic endoscopy. No consensus was achieved for these items in therapeutic intent or emergent endoscopy. The risks of prophylactic platelet transfusions exceed their benefits for outpatient diagnostic paracentesis and diagnostic endosopies. For the other procedures examined, the risks outweigh benefits when platelet count is >20,000/mm 3 . It is uncertain whether risks outweigh benefits below 20,000/mm 3 in other contexts. No consensus was achieved on whether it was permissible to continue or stop systemic anticoagulation. Continuous aspirin was permissible for each procedure. Clopidogrel was permissible for diagnostic and therapeutic paracentesis and diagnostic endoscopy. We found many areas of consensus that may serve as a foundation for a common set of practice metrics for the periprocedural management of coagulopathy in cirrhosis.

Objective: To evaluate long-term oncologic outcomes of patients post–living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. Background: LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). Methods: Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. Results: Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% (P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% (P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%. Conclusions: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.

Immunosuppression after liver transplantation is essential for preventing allograft rejection. However, long-term drug toxicity and associated complications necessitate investigation of immunosuppression minimization and withdrawal protocols. Development of such protocols is hindered by reliance on current paradigms for monitoring allograft function and rejection status. The current standard of care for diagnosis of rejection is histopathologic assessment and grading of liver biopsies in accordance with the Banff Rejection Activity Index. However, this method is limited by cost, sampling variability, and interobserver variation. Moreover, the invasive nature of biopsy increases the risk of patient complications. Incorporating noninvasive techniques may supplement existing methods through improved understanding of rejection causes, hepatic spatial architecture, and the role of idiopathic fibroinflammatory regions. These techniques may also aid in quantification and help integrate emerging -omics analyses with current assessments. Alternatively, emerging noninvasive methods show potential to detect and distinguish between different types of rejection while minimizing risk of adverse advents. Although biomarkers have yet to replace biopsy, preliminary studies suggest that several classes of analytes may be used to detect rejection with greater sensitivity and in earlier stages than traditional methods, possibly when coupled with artificial intelligence. Here, we provide an overview of the latest efforts in optimizing the diagnosis of rejection in liver transplantation.

Abstract Interest in anonymous nondirected living organ donation is increasing in the United States and a small number of transplantation centers are accumulating an experience regarding nondirected donation in living donor liver transplantation. Herein, we review current transplant policy, discuss emerging data, draw parallels from nondirected kidney donation, and examine relevant considerations in nondirected living liver donation. We aim to provide a consensus guidance to ensure safe evaluation and selection of nondirected living liver donors and a schema for just allocation of nondirected grafts.

Background. Survival after living donor liver transplantation (LDLT) in the United States is excellent. However, the significance of pretransplant kidney disease on outcomes in this population is poorly understood. Methods. This was a retrospective cohort study of 2806 LDLT recipients nationally between January 2010 and June 2020. Recipients with estimated glomerular filtration rate <40 mL/min/1.73 m2 (eGFR-low) or requiring dialysis were compared. Multivariable survival analyses evaluated (1) eGFR-low as a predictor of post-LDLT survival and (2) the survival of LDLT versus deceased donor liver transplant (DDLT) alone with eGFR-low. Results. From 2010 to 2020, 140 (5.0%) patients had eGFR-low and 18 (0.6%) required dialysis pre-LDLT. The number of LDLTs requiring dialysis between 2017 and 2020 outnumbered the prior 7 y. Overall LDLT experience was greater at centers performing LDLT in recipients with renal dysfunction (P < 0.001). LDLT recipients with eGFR-low had longstanding renal dysfunction: mean eGFR 3–6 mo before LDLT 42.7 (±15.1) mL/min/1.73 m2. Nearly half (5/12) of eGFR-low recipients with active kidney transplant (KT) listing at LDLT experienced renal recovery. Five patients underwent early KT after LDLT via the new “safety net” policy. Unadjusted survival after LDLT was worse with eGFR-low (hazard ratio 2.12 versus eGFR ≥40 mL/min/1.73 m2; 95% confidence interval, 1.47-3.05; P < 0.001), but no longer so when accounting for mean eGFR 3–6 mo pre-LDLT (hazard ratio, 1.27; 95% confidence interval, 0.82-1.95; P = 0.3). The adjusted survival of patients with eGFR-low receiving LDLT versus deceased donor liver transplant alone was not different (P = 0.08). Conclusions. Overall, outcomes after LDLT with advanced renal dysfunction are acceptable. These findings are relevant given the recent “safety net” KT policy.

Since the introduction of simultaneous liver-kidney transplantation (SLKT) in the 1960s, the potential for immunological protection from the liver allograft to a simultaneously transplanted kidney has been recognized. Due to expanded indications and changes in allocation policies, there has been increased utilization of SLKT. Despite growing experience, a lack of consensus exists regarding the extent of the immunological privilege of the liver the role for donor-specific HLA antibody (DSA) and crossmatch testing, and appropriateness of modern immunosuppression protocols in SLKT recipients. This review provides a detailed analysis of SLKT outcomes in the context of these factors, suggesting that although the liver can reduce the incidence of antibody-mediated rejection, attention should be given to liver allograft function, previous failed transplants, and other risk factors in pretransplant risk assessment. Current methods of DSA and crossmatch testing in SLKT are also discussed, and the role of specific DSA (high mean fluorescence intensity antibody, C1q+ binding) and their potential importance in posttransplant risk assessment are examined. Finally, trends in SLKT immunosuppression are discussed, including the use of nondepleting agents for induction and de-escalating use of steroids for maintenance immunosuppression. Ongoing research, including multicenter or randomized trials, will be necessary to optimize immune-related outcomes in SLKT recipients.

Surgical innovation and multidisciplinary management have allowed children born with univentricular physiology congenital heart disease to survive into adulthood. An estimated global population of 70 000 patients have undergone the Fontan procedure and are alive today, most of whom are <25 years of age. Several unexpected consequences of the Fontan circulation include Fontan-associated liver disease. Surveillance biopsies have demonstrated that virtually 100% of these patients develop clinically silent fibrosis by adolescence. As they mature, there are increasing reports of combined heart-liver transplantation resulting from advanced liver disease, including bridging fibrosis, cirrhosis, and hepatocellular carcinoma, in this population. In the absence of a transplantation option, these young patients face a poor quality of life and overall survival. Acknowledging that there are no consensus guidelines for diagnosing and monitoring Fontan-associated liver disease or when to consider heart transplantation versus combined heart-liver transplantation in these patients, a multidisciplinary working group reviewed the literature surrounding Fontan-associated liver disease, with a specific focus on considerations for transplantation.