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Use of grafts from donation after circulatory death (DCD) as a strategy to increase the pool of transplantable livers has been limited due to poorer recipient outcomes compared with donation after brain death (DBD). We examined outcomes of recipients of failed DCD grafts who were selected for relisting with regard to waitlist mortality and patient and graft survival after retransplant. From the Scientific Registry of Transplant Recipients database, we identified 1820 adults who underwent first deceased donor liver transplant January 1, 2004 to June 30, 2011, and were relisted due to graft failure; 12.7% were DCD recipients. Compared with DBD recipients, DCD recipients had better waitlist survival (90-day mortality: 8%, DCD recipients; 14-21%, DBD recipients). Of 950 retransplant patients, 14.5% were prior DCD recipients. Graft survival after second liver transplant was similar for prior DCD (28% graft failure within 1 year) and DBD recipients (30%). Patient survival was slightly better for prior DCD (25% death within 1 year) than DBD recipients (28%). Despite higher overall graft failure and morbidity rates, survival of prior DCD recipients who were selected for relisting and retransplant was not worse than survival of DBD recipients.

This exploratory phase II study evaluated the safety and efficacy of belatacept in de novo adult liver transplant recipients. Patients were randomized (N=260) to one of the following immunosuppressive regimens: (i) basiliximab+belatacept high dose [HD]+myc

We present simulation results on the effect of a helium nanodroplet environment on the fragmentation dynamics of embedded molecular systems. The helium atoms are treated explicitly, with zero-point effects taken into account through an effective helium-helium interaction potential. The ionized neon tetramer is used as a model molecular system because, like all the small rare-gas clusters, it fragments extensively upon ionization. All the nonadiabatic effects between electronic states of the ionized neon cluster are taken into account. The results reveal a predominance of Ne2+ and HepNe2+ fragments and the absence of bare Ne+ fragments, in agreement with available experimental data. The neutral monomer fragments exhibit a rather wide kinetic energy distribution that can be fitted to the sum of two Boltzmann distributions, one with a low kinetic energy and the other with a higher kinetic energy. This indicates that cooling by helium atom evaporation is more efficient than was believed so far, as suggested by recent experimental results. Purely classical calculations are shown to strongly overestimate the amount of cage effect (cooling), clearly indicating the need to take into account zero-point effects. [ABSTRACT FROM AUTHOR]

We present simulation results on the effect of a helium nanodroplet environment on the fragmentation dynamics of embedded molecular systems. The helium atoms are treated explicitly, with zero-point effects taken into account through an effective helium-helium interaction potential. The ionized neon tetramer is used as a model molecular system because, like all the small rare-gas clusters, it fragments extensively upon ionization. All the nonadiabatic effects between electronic states of the ionized neon cluster are taken into account. The results reveal a predominance of Ne2+ and HepNe2+ fragments and the absence of bare Ne+ fragments, in agreement with available experimental data. The neutral monomer fragments exhibit a rather wide kinetic energy distribution that can be fitted to the sum of two Boltzmann distributions, one with a low kinetic energy and the other with a higher kinetic energy. This indicates that cooling by helium atom evaporation is more efficient than was believed so far, as suggested by recent experimental results. Purely classical calculations are shown to strongly overestimate the amount of cage effect (cooling), clearly indicating the need to take into account zero-point effects. [ABSTRACT FROM AUTHOR]

The article presents a brief ethnographic study of the Chilula Indians who formerly occupied the Redwood Creek Basin of Humboldt County, California. The focus of the study includes the religion and worldview of the Chilula as perceived and practiced during the processes of childbirth, puberty ceremony, death and healing. The author believes the information is important for several reasons: although extensive research has been conducted on the neighboring tribes of the Chilula such as the Yurok and Hupa, relatively little is known about the Chilula. Except for a small collection of notes provided by anthropologist Pliny Goddard in the year 1914, an actual analysis of the Chilula religion and worldview is not available for interpretation and study. Secondly, the new study includes material on the role, function, and perspective of Chilula women. Cultural material on the significance of Indian women is critically lacking in contemporary curriculum. And thirdly, the author believes the Chilula religious processes and psychological world view may have particular meaning and relevance to the concepts of humanistic psychology, which focuses on growth, being, self-actualization, higher values, naturalness, transcendental experience, peak experience and spirituality of the self and group.

The adverse effects of electrochemical bubbles on the performance of gas-evolving electrodes are well known, but studies on the degree of adhered bubble-caused inactivation, and how inactivation changes during bubble evolution are limited. We study electrode inactivation caused by oxygen evolution while using surface engineering to control bubble formation. We find that the inactivation of the entire projected area, as is currently believed, is a poor approximation which leads to non-physical results. Using a machine learning-based image-based bubble detection method to analyze large quantities of experimental data, we show that bubble impacts are small for surface engineered electrodes which promote high bubble projected areas while maintaining low direct bubble contact. We thus propose a simple methodology for more accurately estimating the true extent of bubble inactivation, which is closer to the area which is directly in contact with the bubbles.

Background & Aims: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes., Methods: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection., Results: Among 91 eligible patients, with a median (IQR) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years 0.72, 95% CI 0.53-0.99, p = 0.044) and ICI washout time (aHR per 1 week 0.92, 95% CI 0.86-0.99, p = 0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p = 0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8] vs. 8.0 [9.0]; p = 0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p = 0.032)., Conclusion: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations., Impact and Implications: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitor use prior to liver transplantation suggest acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without immune checkpoint inhibitor exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

In 2022, liver transplant activity continued to increase in the United States, with an all-time high of 9,527 transplants performed, representing a 52% increase over the past decade (2012-2022). Of these transplants, 8,924 (93.7%) were from deceased donors and 603 (6.3%) were from living donors. Liver transplant recipients were 94.5% adult and 5.5% pediatric. The overall size of the liver transplant waiting list contracted, with more patients being removed than added, although 10,548 adult patients still remained on the waiting list at the end of 2022. Alcohol-associated liver disease continued to be the leading diagnosis among both candidates and recipients, followed by metabolic dysfunction-associated steatohepatitis. Simultaneous liver-kidney transplant was the most common multiorgan combination, with 800 liver-kidney transplants performed in 2022; in addition, there were 303 new listings for kidney transplant via the safety net mechanism. Among adults added to the liver waiting list in 2021, 39.9% received a deceased donor liver transplant within 3 months; 45.7%, within 6 months; and 54.5%, within 1 year. Pretransplant mortality decreased to 12.3 deaths per 100 patient-years in 2022, although still 15.6% of removals from the waiting list were for death or being too sick for transplant. Graft and patient survival outcomes after deceased donor liver transplant improved, approximating pre-COVID-19 pandemic levels, with 5.1% mortality observed at 6 months; 6.8%, at 1 year; 12.7%, at 3 years; 19.8%, at 5 years; and 35.7%, at 10 years. Five-year graft and patient survival rates after living donor liver transplant exceeded those of deceased donor liver transplant. Candidates receiving model for end-stage liver disease exception points for hepatocellular carcinoma constituted 15.5% of transplants performed in 2022, with similar transplant rates and posttransplant outcomes compared to cases without hepatocellular carcinoma exception. In 2022, more pediatric liver transplant candidates were added to the waiting list and underwent transplant compared with either of the preceding 2 years, with an uptick in living donor liver transplant volume. Although pretransplant mortality has improved after the recent policy change prioritizing pediatric donors for pediatric recipients, still, in 2022, 50 children died or were removed from the waiting list for being too sick to undergo transplant. Posttransplant mortality among pediatric liver transplant recipients remained notable, with death occurring in 4.0% at 6 months, 6.0% at 1 year, 8.2% at 3 years, 9.8% at 5 years, and 13.9% at 10 years. Similar to adult living donor recipients, pediatric living donor recipients had better 5-year patient survival compared with deceased donor recipients., (Copyright © 2024. Published by Elsevier Inc.)

Acute Liver Failure (ALF) is a life-threatening illness characterized by the rapid onset of abnormal liver biochemistries, coagulopathy, and the development of hepatic encephalopathy. Extracorporeal bioengineered liver (BEL) grafts could offer a bridge therapy to transplant or recovery. The present study describes the manufacture of clinical scale BELs created from decellularized porcine-derived liver extracellular matrix seeded entirely with human cells: human umbilical vein endothelial cells (HUVECs) and primary human liver cells (PHLCs). Decellularized scaffolds seeded entirely with human cells were shown to adhere to stringent sterility and safety guidelines and demonstrated increased functionality when compared to grafts seeded with primary porcine liver cells (PPLCs). BELs with PHLCs were able to clear more ammonia than PPLCs and demonstrated lower perfusion pressures during patency testing. Additionally, to determine the full therapeutic potential of BELs seeded with PHLCs, longer culture periods were assessed to address the logistical constraints associated with manufacturing and transporting a product to a patient. The fully humanized BELs were able to retain their function after cold storage simulating a product transport period. Therefore, this study demonstrates the manufacture of bioengineered liver grafts and their potential in the clinical setting as a treatment for ALF.

A recently discovered phenomenon in which crystalline structures grown from evaporating drops of saline water self-eject from superhydrophobic materials has introduced new possibilities for the design of anti-fouling materials and sustainable processes. Some of these possibilities include evaporative heat exchange systems using drops of saline water and new strategies for handling/processing waste brines. However, the practical limits of this effect using realistic, non-ideal source waters have yet to be explored. Here, we explore how the presence of various model aquatic contaminants (colloids, surfactants, and calcium salt) influences the self-ejection phenomena. Counterintuitively, we find that the addition of "contaminant" chemistries can enable ejection under conditions where ejection was not observed for waters containing only sodium chloride salt (e.g., from smooth hydrophobic surfaces), and that increased concentrations of both surfactants and colloids lead to longer ejection lengths. This result can be attributed to decreased crystallization nucleation time caused by the presence of other species in water.

Liver transplantation (LT) is a life-saving treatment for patients with acute liver failure (ALF). Currently, there are few detailed data regarding long-term outcomes after LT for ALF. We combined prospective data from the Acute Liver Failure Study Group (ALFSG) Registry with those of the Scientific Registry of Transplant Recipients (SRTR) to assess outcomes among consecutive patients with ALF listed for LT. Cohort analysis of detailed pretransplantation data for patients listed for LT for ALF in the ALFSG Registry between January 1998 and October 2018 matched with transplantation-related data from the SRTR. Primary outcomes were 1- and 3-year post-LT patient survival. Secondary outcome was receipt of LT; independent associations with successful receipt of LT were determined using multivariable logistic regression. Of 624 patients with ALF listed for LT, 398 (64%) underwent LT, 100 (16%) died without LT, and 126 (20%) recovered spontaneously. Among LT recipients, etiologies included seronegative/indeterminate (22%), drug-induced liver injury (18%), acetaminophen overdose (APAP; 16%), and viral hepatitis (15%). The 1- and 3-year post-LT patient survival rates were 91% and 90%, respectively. Comparing those dying on the waiting list versus with those who received LT, the former had more severe multiorgan failure, reflected by increased vasopressor use (65% vs. 22%), mechanical ventilation (84% vs. 57%), and renal replacement therapy (57% vs. 30%; p  < 0.0001 for all). After adjusting for relevant covariates, age (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.00-1.04), APAP etiology (aOR 2.72, 95% CI 1.42-5.23), requirement for vasopressors (aOR 4.19, 95% CI 2.44-7.20), Grade III/IV hepatic encephalopathy (aOR 2.47, 95% CI 1.29-4.72), and Model for End-Stage Liver Disease (MELD) scores (aOR 1.05, 95% CI 1.02-1.09; p  < 0.05 for all) were independently associated with death without receipt of LT. Post-LT outcomes for ALF are excellent in this cohort of very ill patients. The development of multiorgan failure while on the transplantation list and APAP ALF etiology were associated with a lower likelihood of successful receipt of LT., (Copyright © 2023 American Association for the Study of Liver Diseases.)

In 2021, liver transplant volume continued to grow, with a record 9,234 transplants performed in the United States, 8,665 (93.8%) from deceased donors and 569 (6.2%) from living donors. There were 8,733 (94.6%) adult and 501 (5.4%) pediatric liver transplant recipients. An increase in the number of deceased donor livers corresponded to an increase in the overall transplant rate and shorter waiting times, although still 10.0% of livers that were recovered were not transplanted. Alcohol-associated liver disease was the leading indication for both waitlist registration and liver transplant in adults, outpacing nonalcoholic steatohepatitis, while biliary atresia remained the leading indication for children. Related to allocation policy changes implemented in 2019, the proportion of liver transplants performed for hepatocellular carcinoma has decreased. Among adult candidates listed for liver transplant in 2020, 37.7% received a deceased donor liver transplant within 3 months, 43.8% within 6 months, and 53.3% within 1 year. Pretransplant mortality improved for children following implementation of acuity circle-based distribution. Short-term graft and patient survival outcomes up to 1 year worsened for adult deceased and living donor liver transplant recipients, which is a reversal of previous trends and coincided with the onset of the COVID-19 pandemic in early 2020. Longer-term outcomes among adult deceased donor liver transplant recipients were unaffected, with overall posttransplant mortality rates of 13.3% at 3 years, 18.6% at 5 years, and 35.9% at 10 years. Pretransplant mortality improved for children following implementation of acuity circle-based distribution and prioritization of pediatric donors to pediatric recipients in 2020. Pediatric living donor recipients had superior graft and patient survival outcomes compared with deceased donor recipients at all time points., (Copyright © 2023. Published by Elsevier Inc.)

Objective: The incidence of alcohol-associated liver disease (ALD) is increasing, and weight loss surgery is more common due to the obesity epidemic. Roux-en-Y gastric bypass (RYGB) is associated with alcohol use disorder and ALD; however, its impact on outcomes in patients hospitalised for alcohol-associated hepatitis (AH) is unclear., Design: We performed a single-centre, retrospective study of patients with AH from June 2011 to December 2019. Primary exposure was the presence of RYGB. The primary outcome was inpatient mortality. Secondary outcomes included overall mortality, readmissions and cirrhosis progression., Results: 2634 patients with AH met the inclusion criteria; 153 patients had RYGB. Median age of the entire cohort was 47.3 years; median Model for End Stage Liver Disease - Sodium (MELD-Na) was 15.1 in the study group versus 10.9 in the control group. There was no difference in inpatient mortality between the two groups. On logistic regression, increased age, elevated body mass index, MELD-Na >20 and haemodialysis were all associated with higher inpatient mortality. RYGB status was associated with increased 30-day readmission (20.3% vs 11.7%, p<0.01), development of cirrhosis (37.5% vs 20.9%, p<0.01) and overall mortality (31.4% vs 24%, p=0.03)., Conclusions: Patients with RYGB have higher rates of readmissions, cirrhosis and overall mortality after discharge from hospital for AH. Allocation of additional resources on discharge may improve clinical outcomes and reduce healthcare expenditure in this unique patient population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: HCC is a leading cause of mortality in patients with advanced liver disease and is associated with significant morbidity. Despite multiple available curative and palliative treatments, there is a lack of systematic evaluation of patient-reported outcomes (PROs) in HCC., Approach and Results: The American Association for the Study of Liver Diseases Practice Metrics Committee conducted a scoping review of PROs in HCC from 1990 to 2021 to (1) synthesize the evidence on PROs in HCC and (2) provide recommendations on incorporating PROs into clinical practice and quality improvement efforts. A total of 63 studies met inclusion criteria investigating factors associated with PROs, the relationship between PROs and survival, and associations between HCC therapy and PROs. Studies recruited heterogeneous populations, and most were cross-sectional. Poor PROs were associated with worse prognosis after adjusting for clinical factors and with more advanced disease stage, although some studies showed better PROs in patients with HCC compared to those with cirrhosis. Locoregional and systemic therapies were generally associated with a high symptom burden; however, some studies showed lower symptom burden for transarterial radiotherapy and radiation therapy. Qualitative studies identified additional symptoms not routinely assessed with structured questionnaires. Gaps in the literature include lack of integration of PROs into clinical care to guide HCC treatment decisions, unknown impact of HCC on caregivers, and the effect of palliative or supportive care quality of life and health outcomes., Conclusion: Evidence supports assessment of PROs in HCC; however, clinical implementation and the impact of PRO measurement on quality of care and longitudinal outcomes need future investigation., (© 2022 American Association for the Study of Liver Diseases.)

The adverse effects of electrochemical bubbles on the performance of gas-evolving electrodes have been extensively studied. However, the ways in which bubbles dynamically alter the electrochemically active surface area during bubble evolution are not well understood. Here, we study hydrogen evolution at industrially relevant current densities by using controlled microtexture to examine this fundamental relationship. Surprisingly, the most densely microtextured electrodes have the lowest performance on an active surface area basis. Using high-speed imaging, we show that the benefits of microtexture to release smaller bubbles more consistently are outweighed by the inactivation induced by bubbles growing within the denser microtexture, causing these performance limitations. Additionally, we show that the area beneath adhered bubbles is electrochemically active, contrary to currently held assumptions. Our study therefore has broad implications for electrode design to avoid ineffective use of precious catalyst materials, which is especially critical for porous electrodes and three-dimensional structures with high specific surface areas.

Competing Interests: The authors declare no funding or conflicts of interest.

This year was marked by the COVID-19 pandemic, which altered transplant program activity and affected waitlist and transplant outcomes. Still, 8906 liver transplants were performed, an all-time high, across 142 centers in the United States, and pretransplant as well as graft and patient survival metrics, continued to improve. Living donation activity decreased after several years of growth. As of June 30, 2020, 98989 liver transplant recipients were alive with a functioning graft, and in the context of increasing liver transplant volume, the size of both the adult and pediatric liver transplant waitlists have decreased. On February 4, 2020, shortly before the pandemic began, a new liver distribution policy based on acuity circles was implemented, replacing donor service area- and region-based boundaries. A policy change to direct pediatric livers to pediatric recipients led to an increase in deceased donor transplant rates and a decrease in pretransplant mortality rate among children, although the absolute number of pediatric transplants did not increase in 2020. Among adults, alcohol-associated liver disease became the predominant indication for liver transplant in 2020. After implementation of the National Liver Review Board and lower waitlist priority for most exception cases in 2019, fewer liver transplants were being performed via exception points, and the transplant rate between those with and without hepatocellular carcinoma has equalized. Women continue to experience higher pretransplant mortality and lower rates of liver transplant than men., (.)

The novel use of carbon dioxide (CO 2 ) electroreduction to generate carbon-based products which do not contribute to the greenhouse effect has promoted the vision of carbon dioxide as a renewable feedstock for future clean fuel production. Depending on the material choice for the electrocatalysis, a certain variety of products is expected from the carbon dioxide reduction reaction (CO2RR). However, as the CO 2 concentration in areas close to the working electrode (relative to the diffusive boundary layer) decreases as it is being consumed and transformed into other products, the generation of H 2 is favored to the detriment of CO 2 electroreduction. Therefore, the extent to which H 2 is produced can be used as a metric to evaluate the efficiency of CO2RR. This article proposes a model that accounts for the modes in which aqueous gas depletion evolves over time and affects the long-term CO 2 electroreduction and the corresponding pH evolution near the electrode's surface. For the latter, two main contributions are distinguished: gas depletion due to CO 2 consumption and ion generation in areas close to the electrocatalyst surface. pH is then suggested as an accurate and indirect means to measure CO 2 concentration in a liquid electrolyte. We conclude that CO 2 depletion causes a strong decay in the electrochemical reaction efficiency. In the end, we discuss several methods which may delay the onset of the adverse effects caused by gas depletion, such as the utilization of pulsed electroreduction, cycling the applied current to electrodes on and off periodically.

Background: Bariatric surgery (BS) may be associated with significant malabsorption and nutritional deficiencies., Methods: Between March 1987 and January 2017, we performed 922 liver transplants (LT) at our institution; 33 had antecedent BS. We matched the BS cohort to LT recipients without BS (1:3 matching) based on exact matching for gender and cancer and inverse variance matching for age, LT body mass index, MELD score, and transplant date., Results: We analyzed outcomes in 132 LT recipients (33 BS; 99 non-BS). The BS cohort comprised 26 (79%) women with a mean age of 52.4 years. The BS procedures included 20 Roux-en-Y gastric bypass (61%), 6 jejunoileal bypass (18%), 3 gastric band (9%), 2 sleeve gastrectomy (6%), and 1 duodenal switch (3%). The primary indications for LT listing were alcoholic cirrhosis (9; 27%), nonalcoholic steatohepatitis (7; 21%), hepatitis C (8; 24%), and hepatocellular carcinoma (3; 9%). At LT, body mass index for the BS cohort was 29.6, and MELD was 24. Compared with matched controls, BS recipients did not have longer LT length of hospital stay (17.8 versus 15.7 d, P = 0.71), longer intensive care unit length of stay (5.3 versus 4.1 d, P = 0.16), or higher 30-day complication rate (76% versus 85%, P = 0.43). Overall patient survival was similar (1- and 3-y survival was 90.1% and 75.9% for BS; 90.9% and 76.4% for non-BS, P = 0.34)., Conclusions: A history of BS does not portend a deleterious effect on LT outcomes., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: For liver transplant candidates on the waiting list, deciding to accept a donor organ with known or potential risk factors can be stressful and can lead to declined offers. Current education for patients and family often takes place during transplant evaluations and can be overwhelming and result in low retention and poor understanding of donor quality., Methods: In the first phase, we sought to understand provider experiences when counseling patients about donor risks and donor offers. We conducted interviews and focus groups with liver transplant providers at 1 local center and at a national clinician conference. Twenty providers participated: 15 hepatologists and 5 surgeons. The provider feedback was used to create an initial outline of content that is consistent with decision support frameworks. In a second phase, graphic design collaborators created mockups of a patient-friendly tool. We reviewed mockups with 4 transplant coordinators and 9 liver transplant candidates for feedback on clarity and utility to prepare for an organ offer. Patient responses allowed a comparison of perceived readiness to receive an offer call before and after viewing mockups., Results: We identified themes relating to the offer process, repetition and timing of education, and standardization and tailoring of content. The results indicated a gap in available education after the evaluation session, and information specific to offer decisions is needed. Patient feedback emphasized the need to review the offer process before a real offer., Conclusions: Patients and providers responded favorably to a patient tool addressing existing gaps in education while waiting for a donor offer. Additional patient, family, and provider feedback will guide the development of an interactive tool to prepare patients and families for an offer decision., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

This year was notable for changes to exception points determined by the geographic median allocation Model for End-Stage Liver Disease (MELD) and implementation of the National Liver Review Board, which took place on May 14, 2019. The national acuity circle liver distribution policy was also implemented but reverted to donor service area- and region-based boundaries after 1 week. In 2019, growth continued in the number of new waiting list registrations (12,767) and transplants performed (8,896), including living-donor transplants (524). Compared with 2018, living-donor liver transplants increased 31%. Women continued to have a lower deceased-donor transplant rate and a higher pretransplant mortality rate than men. The median waiting time for candidates with a MELD of 15-34 decreased, while the number of transplants performed for patients with exception points decreased. These changes may have been related to the policy changes that took effect in May 2019, which increased waiting list priority for candidates without exception status. Hepatitis C continued to decline as an indication for liver transplant, as the proportion of liver transplant recipients with alcohol-related liver disease and clinical profiles consistent with non-alcoholic steatohepatitis increased. Graft and patient survival have improved despite changing recipient demographics including older age, higher MELD, and higher prevalence of obesity and diabetes., (.)

Competing Interests: The authors declare no funding or conflicts of interest.

Background: Tenofovir disoproxil fumarate (TDF) is associated with reduced bone density in patients with human immunodeficiency virus, but the effect of TDF on bone density in liver transplant (LT) recipients is unknown., Methods: We performed a single-center, retrospective study of LT recipients with hepatitis B taking TDF compared to a control group with non-hepatitis B virus viral hepatitis. The primary outcome was reduced bone density, defined as femoral neck or lumbar T-score less than -1. Other outcomes included mean T-score and fractures., Results: Three hundred ninety-three patients were studied: 52 patients in the TDF group and 341 patients in the control group; 64.3% patients in the TDF group had reduced bone density vs 71.4% in the control group (P = .58) before LT, compared to 75% and 81.5% (P = .57), respectively, after LT. Mean posttransplant lumbar T-scores were lower in the TDF group (-1.74 vs -0.75, P = .04). There was no difference between the 2 groups for the other outcomes. In a multivariate Cox proportional hazards model, TDF use did not affect the risk of post-LT reduced bone density (hazard ratio = 0.99; 95% confidence interval, 0.56-1.76; P = .97)., Conclusion: TDF use was not associated with reduced bone mineral density or increased rates of fractures in LT recipients compared to controls in this study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV). The impact of DAAs on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains uncertain., Objective: We aimed to evaluate the risk of HCC recurrence in LT recipients cleared of HCV with DAAs at the time of LT compared to a control group of LT recipients who were viremic at the time of LT., Methods: The study was a single-center, retrospective cohort study of patients undergoing LT for HCV-related HCC from 2002 to 2017. We compared time to post-LT HCC recurrence in patients with a sustained virological response (SVR) from DAAs prior to LT (DAA group) to patients who were viremic at LT (HCV+ group) using Kaplan-Meier analysis. We performed a secondary analysis comparing post-LT HCC recurrence in the DAA group to LT recipients with SVR from interferon-based treatment prior to LT (IFN group)., Results: One hundred fifty-one patients underwent LT for HCC related to HCV: 34 patients in DAA group, 95 patients in HCV+ group, and 22 in IFN group. Kaplan-Meier estimates of being HCC free were 96.2, 96.2, and 78.8% at 6, 12, and 24 months in DAA group, respectively, and 100, 98.6, and 95.8% at 6, 12, and 24 months in the HCV+ group, respectively; p = 0.08. There was no difference observed for HCC recurrence between the DAA and IFN groups. In a multivariate Cox proportional hazards model, DAA use increased the risk of post-LT HCC recurrence (HR 5.2, 95% CI 0.9-29.81, p = 0.07)., Conclusions: A strong trend was observed on both Kaplan-Meier and multivariate analyses toward increased post-LT HCC recurrence in patients who achieved SVR prior to LT with DAAs compared to patients who were viremic at LT. Caution is required when considering pre-LT treatment of HCV with DAAs in patients with HCC., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

Purpose of Review: Prior to the enactment of the National Organ Transplant Act in 1984, there was no organized system to allocate donor organs in the United States. The process of liver allocation has come a long way since then, including the development and implementation of the Model for End-stage Liver Disease, which is an objective estimate of risk of mortality among candidates awaiting liver transplantation., Recent Findings: The Liver Transplant Community is constantly working to optimize the distribution and allocation of scare organs, which is essential to promote equitable access to a life-saving procedure in the setting of clinical advances in the treatment of liver disease. Over the past 17 years, many changes have been made. Most recently, liver distribution changed such that deceased donor livers will be distributed based on units established by geographic circles around a donor hospital rather than the current policy, which uses donor service areas as the unit of distribution. In addition, a National Liver Review Board was created to standardize the process of determining liver transplant priority for candidates with exceptional medical conditions. The aim of these changes is to allocate and distribute organs in an efficient and equitable fashion., Summary: The current review provides a historical perspective of liver allocation and the changing landscape in the United States.

Variations in candidate and donor acceptance criteria may influence access and mortality for liver transplantation. We sought to understand how recipient and donor characteristics vary across centers and how patients interpret this information, and we used these data to develop a tool to provide tailored information to candidates seeking a center (www.transplantcentersearch.org). We analyzed liver recipient data from the Scientific Registry of Transplant Recipients to determine how recipient and donor characteristics (eg, age, Medicaid use, and human immunodeficiency virus status) varied across programs. Data included recipients and donors at each US program between January 1, 2015, and December 31, 2017. The variation in characteristics was plotted with centers stratified by total transplant volume and by volume of each characteristic. A subset of characteristics was plotted to show variation over 3 years. We created mockups of potential reports displaying recipient characteristics alongside pretransplant and posttransplant outcomes and solicited feedback at patient and family interviews and focus groups, which included 39 individuals: 10 pilot interviews with candidates seeking liver transplant at the University of Minnesota-Fairview (UMNF) and 5 focus groups with 13 UMNF candidates, 6 UMNF family members, and 10 national recipients. Transcripts were analyzed using a thematic analysis. Several themes emerged: (1) Candidates experience gaps in existing education about center options; (2) patients requested information about how selection criteria might impact access to transplant; and (3) information tailored to a candidate's medical characteristics can inform decisions. Characteristics shown on mockups varied across centers (P < 0.01). Variation was widespread for small and large centers. In conclusion, variation exists in recipient and donor characteristics across centers. Liver transplant patients provide positive feedback upon viewing patient-specific search tools., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Background: In response to calls for an increased focus on pretransplant outcomes and other patient-centered metrics in public reports of center outcomes, a mixed methods study evaluated how the content and presentation style of new information influences decision-making. The mixed methods design utilized qualitative and quantitative phases where the strengths of one method help address limitations of the other, and multiple methods facilitate comparing results., Methods: First, a series of organ-specific focus groups of kidney, liver, heart, and lung patients helped to develop and refine potential displays of center outcomes and understand patient perceptions. A subsequent randomized survey included adult internet users who viewed a single, randomly-selected variation of 6 potential online information displays. Multinomial regression evaluated the effects of graphical presentations of information on decision-making., Results: One hundred twenty-seven candidates and recipients joined 23 focus groups. Survey responses were analyzed from 975 adults. Qualitative feedback identified patient perceptions of uncertainty in outcome metrics, in particular pretransplant metrics, and suggested a need for clear guidance to interpret the most important metric for organ-specific patient mortality. In the randomized survey, only respondents who viewed a note indicating that transplant rate had the largest impact on survival chose the hospital with the best transplant rate over the hospital with the best posttransplant outcomes (marginal relative risk and 95% confidence interval, 1.161.501.95)., Conclusions: The presentation of public reports influenced decision-making behavior. The combination of qualitative and quantitative research helped to guide and enhance understanding of the impacts of proposed changes in reported metrics.

We report a case of liver transplant patient who presented with lung masses, found to be Mycobacterium spindle cell pseudotumors. The masses demonstrated hypermetabolic activities on positron emission tomography. Core biopsy revealed sheets of spindle histiocytic cells with abundant acid-fast bacilli identified as Mycobacterium avium-intracellulare complex. This finding is a rare presentation of Mycobacterium infection, mainly nontuberculous Mycobaterium. It is characterized by a benign, spindle cell mass-forming reaction. Most of the reported cases had acquired immune deficiency syndrome or organ transplant. Histopathology illustrating the proliferation of spindle cell shaped histiocytes containing numerous acid-fast bacilli is the gold standard for diagnosis. The standard treatment has not been well established; previously reported cases followed the standard treatment for Mycobacterium based on organ involvement. Our case is the first case to our knowledge that reports pulmonary Mycobacterium spindle cell pseudotumors in a liver transplant recipient., (Copyright © 2019 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Direct acting antivirals (DAAs) have fundamentally changed the treatment of hepatitis C virus (HCV) infection and reduced the discard rate of HCV-infected organs by offering a treatment option with a high likelihood of cure posttransplant. This has spurred increased interest in transplanting organs from HCV-positive donors into recipients both with and without HCV. In this chapter, we examine data from 2007 to 2018 to determine trends in HCV (+) donor transplants across various organ types. Since 2015, willingness to accept HCV (+) organs increased for candidates waitlisted for kidney, lung, heart, and pancreas transplant, but decreased for those listed for intestine transplant. For candidates listed for liver transplant, willingness to accept HCV (+) organs decreased from 2007 to 2017, but began increasing in 2017. Willingness to accept was not concentrated in a single US geographic area, and there was substantial variation among transplant programs and donation service areas. Numbers of anti-HCV (+) donor kidney, heart, lung, and liver transplants have increased considerably in the past few years. Short-term allograft survival for kidney and liver transplant recipients of anti-HCV (+) organs appears to be comparable to that for recipients of anti-HCV (-) organs in an unadjusted analysis. However, an unadjusted analysis indicates that long-term allograft survival may be worse. Kidney transplant between HCV-infected donors and uninfected recipients with posttransplant DAA treatment is an emerging area. Short-term data are promising, with similar 1-year allograft survival compared with HCV-uninfected donor to HCV-uninfected recipient kidney transplants in unadjusted analyses. However, long-term data are lacking and close monitoring in the future is warranted., (.)

Data on adult liver transplants performed in the US in 2018 are notable for (1) continued growth in numbers of new waitlist registrants (11,844) and transplants performed (8250); (2) continued increase in the transplant rate (54.5 per 100 waitlist-years); (3) a precipitous decline in waitlist registrations and transplants for hepatitis-C-related indications; (4) increases in waitlist registrants and recipients with alcoholic liver disease and with clinical profiles consistent with non-alcoholic fatty liver disease; (5) increased use of hepatitis C virus antibody-positive donor livers; and (6) continued improvement in graft survival despite changing recipient characteristics such as older age and higher rates of obesity and diabetes. Variability in transplant rates remained by candidate race, hepatocellular carcinoma status, urgency status, and geography. The volume of pediatric liver transplants was relatively unchanged. The highest rate of pre-transplant mortality persisted for children aged younger than 1 year. Children underwent transplant at higher acuity than in the past, as evidenced by higher model for end-stage liver disease/pediatric end-stage liver disease scores and listings at status 1A and 1B at transplant. Despite higher illness severity scores at transplant, pediatric graft and patient survival posttransplant have improved over time., (.)

Hepatitis C treatment has rapidly evolved with the arrival of direct-acting antiviral therapy. Sustained virologic response (SVR) rates in clinical trials are high but it is unknown how this translates to the immigrant community. Data from December 2013 to September 2015 was collected from a Midwest academic and community practice with a large immigrant population. There were 802 patients with an overall SVR rate of 88%. Ledipasvir/sofosbuvir was associated with favorable response among genotype 1 and 4 patients compared to other regimens (p < 0.001 and p = 0.05). Factors associated with treatment failure included advanced liver disease, male gender, East African/Middle Eastern ethnicity, and non-compliance. Patients with genotype 4 had lower SVR rates than other genotypes (58% vs. 89%, p < 0.001), particularly among East Africans (40% vs. 82% for other ethnicities). Our SVR rate for genotype 4 infection is lower than clinical trials and may be related to cultural, biologic and socioeconomic factors.

Data on adult liver transplants performed in the US in 2017 are notable for (1) continued growth in numbers of new waitlist registrants (11,514) and of transplants performed (8,082); (2) continued increase in the transplant rate (51.5 per 100 waitlist-years); (3) a precipitous decrease in waitlist registrations and transplants for hepatitis C-related indications; (4) reciprocal increases in waitlist registrants and recipients with alcoholic liver disease and with clinical profiles consistent with non-alcoholic fatty liver disease; and (5) continued improvement in graft survival despite changing recipient characteristics such as older age and higher rates of obesity. Variability in transplant rates remained by candidate race, presence of hepatocellular carcinoma, urgency status (status 1A versus model for end-stage liver disease (MELD) score >35), and geography. More than half of all children listed for liver transplant in 2017 were aged younger than 5 years in 2017, and the highest rate of pretransplant mortality persisted for children aged younger than 1 year. Children underwent transplant at higher acuity than the past, as evidenced by higher MELD/pediatric end-stage liver disease scores and listings at status 1A and 1B. Higher acuity at transplant is likely due to lack of access to suitable donor organs, which has been compensated for by persistent trends toward use of partial or split liver grafts and ABO-incompatible grafts. Despite higher illness severity scores at transplant, pediatric graft and patient survival posttransplant have improved over time., (.)

Microfluidics has become a critical tool in research across the biological, chemical, and physical sciences. One important component of microfluidic experimentation is a stable fluid handling system capable of accurately providing an inlet flow rate or inlet pressure. Here, we have developed a syringe pump system capable of controlling and regulating the inlet fluid pressure delivered to a microfluidic device. This system was designed using low-cost materials and additive manufacturing principles, leveraging three-dimensional (3D) printing of thermoplastic materials and off-the-shelf components whenever possible. This system is composed of three main components: a syringe pump, a pressure transducer, and a programmable microcontroller. Within this paper, we detail a set of protocols for fabricating, assembling, and programming this syringe pump system. Furthermore, we have included representative results that demonstrate high-fidelity, feedback control of inlet pressure using this system. We expect this protocol will allow researchers to fabricate low-cost syringe pump systems, lowering the entry barrier for the use of microfluidics in biomedical, chemical, and materials research.

Objectives: Pulmonary nodules are common in patients with hepatocellular carcinoma who are being evaluated for a possible liver transplant., Materials and Methods: In this retrospective study, we analyzed the records of liver transplant recipients at our institution with a primary diagnosis of hepatocellular carcinoma who received transplants between 2000 and 2015. All patients had magnetic resonance imaging-confirmed disease within Milan criteria and a concurrent staging chest computed tomography. Patient survival was estimated using Kaplan-Meier methods and compared between pulmonary nodule characteristic groups. A Cox proportional hazards model was constructed for adjusted analysis., Results: Of the 197 liver transplant recipients who met our study inclusion criteria (median follow-up, 40 mo), 115 (58.4%) had a total of 231 pulmonary nodules, with 57 (49.6%) having multiple nodules and 108 (93.9%) having nodules ≤ 1 cm. The presence of pulmonary nodules did not negatively affect patient survival, per our univariate and multivariate analysis, nor did their presence affect their number, location, laterality, shape, edge, density, or the presence of calcifications (P ≥.05). However, pulmonary nodules ≥ 1 cm were associated with decreased overall survival., Conclusions: In our pretransplant evaluation of patients with hepatocellular carcinoma, pulmonary nodules ≤ 1 cm did not portend worse patient or graft survival posttransplant.

Background: The liver simulated allocation model (LSAM) can be used to study likely effects of liver transplant allocation policy changes on organ offers, acceptance, waitlist survival, and posttransplant survival. Implementation of Share 35 in June 2013 allowed for testing how well LSAM predicted actual changes., Methods: LSAM projections for 1 year of liver transplants before and after the Share 35 policy change were compared with observed data during the same period. Numbers of organs recovered, organ sharing, transplant rates, and waitlist mortality rates (per 100 waitlist years) were evaluated by LSAM and compared with observed data., Results: Candidate, recipient, and donor characteristics in the LSAM cohorts were similar to those in the observed population before and after Share 35. LSAM correctly predicted more accepted organs and fewer discarded organs with Share 35. LSAM also predicted increased regional and national sharing, consistent with observed data, although the magnitude was overestimated. Transplant rates were correctly projected to increase and waitlist death rates to decrease., Conclusions: Although the absolute number of transplants was underestimated and waitlist deaths overestimated, the direction of change was consistent with observed data. LSAM correctly predicted change in discarded organs, regional and national sharing, waitlist mortality, and transplants after Share 35 implementation.

Data on adult liver transplants performed in the US in 2016 are no-table for (1) the largest total number of transplants performed (7841); (2) the shortest median waiting time in recent history (11.3 months); (3) continued reduction in waitlist registrations and transplants for hepatitis C-related indications; (4) increasing numbers of patients whose clinical profiles are consistent with non-alcoholic fatty liver disease; and (5) equilibration of transplant rates in patients with and without hepatocellular carcinoma. Despite the increase in the number of available organs, waitlist mortality remained an important concern. Graft survival rates continued to improve. In 2016, 723 new active candidates were added to the pediatric liver transplant waiting list, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) was stable, 408 active and 169 inactive. The number of pediatric living donor liver transplants decreased from a peak of 79 in 2015 to 62 in 2016, with most from donors closely related to the recipients. Graft survival continued to improve over the past decade among recipients of deceased donor and living donor livers., (.)

Microfluidics are widely used in research ranging from bioengineering and biomedical disciplines to chemistry and nanotechnology. As such, there are a large number of options for the devices used to drive and control flow through microfluidic channels. Commercially available syringe pumps are probably the most commonly used instruments for this purpose, but are relatively high-cost and have inherent limitations due to their flow profiles when they are run open-loop. Here, we present a low-cost ($110) syringe pressure pump that uses feedback control to regulate the pressure into microfluidic chips. Using an open-source microcontroller board (Arduino), we demonstrate an easily operated and programmable syringe pump that can be run using either a PID or bang-bang control method. Through feedback control of the pressure at the inlets of two microfluidic geometries, we have shown stability of our device to within ±1% of the set point using a PID control method and within ±5% of the set point using a bang-bang control method with response times of less than 1 second. This device offers a low-cost option to drive and control well-regulated pressure-driven flow through microfluidic chips.

Several notable developments in adult liver transplantation in the US occurred in 2015. The year saw the largest number of liver transplants to date, leading to reductions in median waiting time, in waitlist mortality for all model for end-stage liver disease categories, and in the number of candidates on the waiting list at the end of the year. Numbers of additions to the waiting list and of liver transplants performed in patients with hepatitis C virus infection decreased for the first time in recent years. However, other diagnoses, such as non-alcoholic fatty liver disease and alcoholic cirrhosis, became more prevalent. Despite large numbers of severely ill patients undergoing liver transplant, graft survival rates continued to improve. The number of new active candidates added to the pediatric liver transplant waiting list in 2015 was 689, down from a peak of 826 in 2005. The number of prevalent pediatric candidates (on the list on December 31 of the given year) continued to decline, to 373 active and 195 inactive candidates. The number of pediatric liver transplants peaked at 613 in 2008 and was 580 in 2015. The number of living donor pediatric liver transplants increased to its highest level, 79, in 2015; most were from donors closely related to the recipients. Pediatric graft survival rates continued to improve., (.)

Background: The probability of liver transplant and death on the waiting list in the United States varies greatly by donation service area (DSA) due to geographic differences in availability of organs and allocation of priority points, making it difficult for providers to predict likely outcomes after listing. We aimed to develop an online calculator to report outcomes by region and patient characteristics., Methods: Using the Scientific Registry of Transplant Recipients database, we included all prevalent US adults aged 18 years or older waitlisted for liver transplant, examined on 24 days at least 30 days apart over a 2-year period. Outcomes were determined at intervals of 30 to 365 days. Outcomes are reported by transplant program, DSA, region, and the nation for comparison, and can be shown by allocation or by laboratory model for end-stage liver disease (MELD) score (6-14, 15-24, 25-29, 30-34, 35-40), age, and blood type., Results: Outcomes varied greatly by DSA; for candidates with allocation MELD 25-29, the 25th and 75th percentiles of liver transplant probability were 30% and 67%, respectively, at 90 days. Corresponding percentiles for death or becoming too sick to undergo transplant were 5% and 9%. Outcomes also varied greatly for candidates with and without MELD exception points., Conclusions: The waitlist outcome calculator highlights ongoing disparities in access to liver transplant and may assist providers in understanding and counseling their patients about likely outcomes on the waiting list.

Background & Aims: Hepatorenal syndrome type 1 (HRS-1) in patients with cirrhosis and ascites is a functional, potentially reversible, form of acute kidney injury characterized by rapid (<2 wk) and progressive deterioration of renal function. Terlipressin is a synthetic vasopressin analogue that acts, via vascular vasopressin V1 receptors, as a systemic vasoconstrictor. We performed a phase 3 study to evaluate the efficacy and safety of intravenous terlipressin plus albumin vs placebo plus albumin in patients with HRS-1., Methods: Adult patients with cirrhosis, ascites, and HRS-1 (based on the 2007 International Club of Ascites criteria of rapidly deteriorating renal function) were assigned randomly to groups given intravenous terlipressin (1 mg, n = 97) or placebo (n = 99) every 6 hours with concomitant albumin. Treatment continued through day 14 unless the following occurred: confirmed HRS reversal (CHRSR, defined as 2 serum creatinine [SCr] values ≤1.5 mg/dL, at least 40 hours apart, on treatment without renal replacement therapy or liver transplantation) or SCr at or above baseline on day 4. The primary end point was the percentage of patients with confirmed CHRSR. Secondary end points included the incidence of HRS reversal (defined as at least 1 SCr value ≤1.5 mg/dL while on treatment), transplant-free survival, and overall survival. The study was performed at 50 investigational sites in the United States and 2 in Canada, from October 2010 through February 2013., Results: Baseline demographic/clinical characteristics were similar between groups. CHRSR was observed in 19 of 97 patients (19.6%) receiving terlipressin vs 13 of 99 patients (13.1%) receiving placebo (P = .22). HRS reversal was achieved in 23 of 97 (23.7%) patients receiving terlipressin vs 15 of 99 (15.2%) receiving placebo (P = .13). SCr decreased by 1.1 mg/dL in patients receiving terlipressin and by only 0.6 mg/dL in patients receiving placebo (P < .001). Decreases in SCr and survival were correlated (r(2) = .882; P < .001). Transplant-free and overall survival were similar between groups. A significantly greater proportion of patients with CHRSR who received terlipressin survived until day 90 than patients who did not have CHRSR after receiving terlipressin (P < .001); this difference was not observed in patients who did vs did not have CHRSR after receiving placebo (P = .28). There were similar numbers of adverse events in each group, but patients in the terlipressin group had more ischemic events., Conclusions: Terlipressin plus albumin was associated with greater improvement in renal function vs albumin alone in patients with cirrhosis and HRS-1. Patients had similar rates of HRS reversal with terlipressin as they did with albumin. ClinicalTrials.gov no: NCT01143246., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)