The Liver Cirrhosis Network Cohort Study: Cirrhosis Definition, Study Population, and Endpoints.

BACKGROUND: One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrhosis. METHODS: The LCN consists of a Scientific Data Coordinating Center (SDCC) and 10 clinical centers whose investigators populate multiple committees. The LCN Definitions and Measurements Committee developed preliminary definitions of cirrhosis and its complications by literature review, expert opinion, and reviewing definition documents developed by other organizations. The Cohort Committee developed the study protocol with the input of the steering committee. RESULTS: The LCN developed a prospective cohort study to describe and predict the rates of incident clinical events pertaining to first decompensation and patient reported outcomes. The LCN developed a pragmatic definition of compensated cirrhosis incorporating clinical, laboratory, imaging, and histological criteria. Definitions of incident and recompensated ascites, overt hepatic encephalopathy, variceal hemorrhage, bleeding due to portal gastropathy, and hepatocellular carcinoma were also codified. CONCLUSION: The LCN Cohort Study design will inform the natural history of cirrhosis in contemporary patients with compensated cirrhosis. The LCN Definitions and Measures Committee developed criteria for the definition of cirrhosis to standardize entry into this multi-center cohort study and standardized criteria for liver-related outcome measures. This effort has produced definitions intended to be both sensitive and specific as well as easily operationalized by study staff such that outcomes critical to the LCN cohort are identified and reported in an accurate and generalizable fashion.

Association of body mass index with post-liver transplant outcomes.

BACKGROUND: Patients with obesity have inferior outcomes after general surgery procedures, but studies evaluating post-liver transplant (LT) outcomes have been limited by small sample sizes or lack of granularity of outcomes. We evaluated the relationship between obesity and post-LT outcomes, including those observed in other populations to be obesity-related. METHODS: Included were 1357 LT recipients prospectively enrolled in the ambulatory pre-LT setting at 8 U.S. CENTERS: Recipient were categorized by body mass index (BMI, kg/m2 ): non-obese (BMI < 30), class 1 obesity (BMI 30-<35), and classes 2-3 obesity (BMI ≥ 35). Post-transplant complications were compared by BMI using Chi-square and rank-sum testing, logistic regression, Kaplan-Meier curves, and Cox regression. RESULTS: Classes 2-3 obesity was associated with higher adjusted odds than non-obesity of venous thrombosis [adjusted odds ratio (aOR) 2.06, 95% CI 1.01-4.23, p = .047] and wound dehiscence (aOR 2.45, 95% CI 1.19-5.06, p = .02). Compared with non-obese recipients, post-LT hospital stay was significantly longer for recipients with classes 2-3 obesity [p = .01; median (Q1-Q3) 9 (6-14) vs. 8 (6-12) days) or class 1 obesity [p = .002; 9 (6-14) vs. 8 (6-11) days].  Likelihood of ICU readmission, infection, discharge to a non-home facility, rejection, 30-day readmission, and 1-year readmission were similar across BMI categories (all p > .05). CONCLUSION: Compared to non-obese recipients, obese recipients had similar post-LT survival but longer hospital stay and higher likelihood of wound dehiscence and venous thrombosis. These findings underscore that obesity alone should not preclude LT, but recipients with obesity should be monitored for obesity-related complications such as wound dehiscence and venous thrombosis.

Transforming the Future of Surgeon-Scientists.

OBJECTIVE: To create a blueprint for surgical department leaders, academic institutions, and funding agencies to optimally support surgeon-scientists. BACKGROUND: Scientific contributions by surgeons have been transformative across many medical disciplines. Surgeon-scientists provide a distinct approach and mindset toward key scientific questions. However, lack of institutional support, pressure for increased clinical productivity, and growing administrative burden are major challenges for the surgeon-scientist, as is the time-consuming nature of surgical training and practice. METHODS: An American Surgical Association Research Sustainability Task Force was created to outline a blueprint for sustainable science in surgery. Leaders from top NIH-sponsored departments of surgery engaged in video and in-person meetings between January and April 2023. A strength, weakness, opportunities, threats analysis was performed, and workgroups focused on the roles of surgeons, the department and institutions, and funding agencies. RESULTS: Taskforce recommendations: (1) SURGEONS: Growth mindset : identifying research focus, long-term planning, patience/tenacity, team science, collaborations with disparate experts; Skill set : align skills and research, fill critical skill gaps, develop team leadership skills; DEPARTMENT OF SURGERY (DOS): (2) MENTORSHIP: Chair : mentor-mentee matching/regular meetings/accountability, review of junior faculty progress, mentorship training requirement, recognition of mentorship (eg, relative value unit equivalent, awards; Mentor: dedicated time, relevant scientific expertise, extramural funding, experience and/or trained as mentor, trusted advisor; Mentee : enthusiastic/eager, proactive, open to feedback, clear about goals; (3) FINANCIAL SUSTAINABILITY: diversification of research portfolio, identification of matching funding sources, departmental resource awards (eg, T-/P-grants), leveraging of institutional resources, negotiation of formalized/formulaic funds flow investment from academic medical center toward science, philanthropy; (4) STRUCTURAL/STRATEGIC SUPPORT: Structural: grants administrative support, biostats/bioinformatics support, clinical trial and research support, regulatory support, shared departmental laboratory space/equipment; Strategic: hiring diverse surgeon-scientist/scientists faculty across DOS, strategic faculty retention/ recruitment, philanthropy, career development support, progress tracking, grant writing support, DOS-wide research meetings, regular DOS strategic research planning; (5) COMMUNITY AND CULTURE: Community: right mix of faculty, connection surgeon with broad scientific community; Culture: building research infrastructure, financial support for research, projecting importance of research (awards, grand rounds, shoutouts); (6) THE ROLE OF INSTITUTIONS: Foundation: research space co-location, flexible start-up packages, courses/mock study section, awards, diverse institutional mentorship teams; Nurture: institutional infrastructure, funding (eg, endowed chairs), promotion friendly toward surgeon-scientists, surgeon-scientists in institutional leadership positions; Expectations: RVU target relief, salary gap funding, competitive starting salaries, longitudinal salary strategy; (7) THE ROLE OF FUNDING AGENCIES: change surgeon research training paradigm, offer alternate awards to K-awards, increasing salary cap to reflect market reality, time extension for surgeon early-stage investigator status, surgeon representation on study section, focused award strategies for professional societies/foundations. CONCLUSIONS: Authentic recommitment from surgeon leaders with intentional and ambitious actions from institutions, corporations, funders, and society is essential in order to reap the essential benefits of surgeon-scientists toward advancements of science.

The liver frailty index is a predictor of healthcare utilization after liver transplantation in older adults.

BACKGROUND: Older adults have higher healthcare utilization after liver transplantation (LT), yet objective risk stratification tools in this population are lacking. We evaluated the Liver Frailty Index (LFI) as one potential tool. METHODS: Ambulatory LT candidates ≥65 years without hepatocellular carcinoma (HCC) who underwent LT from 1/2012 to 6/2022 at 8 U.S. centers were included. Estimates of the difference in median using quantile regression were used to assess the adjusted association between LFI and hospitalized days within 90 days post-LT. RESULTS: Of 131 LT recipients, median (interquartile range [IQR]) (1st -3rd quartiles) age was 68 years (66-70); median pre-LT MELD-Na was 19 (15-24). Median LFI was 4.1 (3.6-4.7); 27% were frail (LFI≥4.5). Median hospitalized days within 90 days post-LT was 11 (7-20). Compared with non-frail patients, frail patients were hospitalized for a median of 5 days longer post-LT (95% CI .30-9.7, p = .04). Each .5 unit increase in pre-LT LFI was associated with an increase of 1.16 days (95%CI .42-2.69, p = .02) in hospitalized days post-LT. CONCLUSION: Among older adults undergoing LT, frailty was associated with more hospitalized days within 90 days after LT. The LFI can identify older adults who might benefit from pre-LT or early post-LT programs which may reduce post-LT healthcare utilization, such as early rehabilitation or post-hospital discharge programs.

Patient randomised controlled trial of technology enabled strategies to promote treatment adherence in liver transplantation: rationale and design of the TEST trial.

BACKGROUND AND AIMS: Liver transplantation is a life-saving procedure for end-stage liver disease. However, post-transplant medication regimens are complex and non-adherence is common. Post-transplant medication non-adherence is associated with graft rejection, which can have long-term adverse consequences. Transplant centres are equipped with clinical staff that monitor patients post-transplant; however, digital health tools and proactive immunosuppression adherence monitoring has potential to improve outcomes. METHODS AND ANALYSIS: This is a patient-randomised prospective clinical trial at three transplant centres in the Northeast, Midwest and South to investigate the effects of a remotely administered adherence programme compared with usual care. The programme monitors potential non-adherence largely levering text message prompts and phenotypes the nature of the non-adhere as cognitive, psychological, medical, social or economic. Additional reminders for medications, clinical appointments and routine self-management support are incorporated to promote adherence to the entire medical regimen. The primary study outcome is medication adherence via 24-hour recall; secondary outcomes include additional medication adherence (ASK-12 self-reported scale, regimen knowledge scales, tacrolimus values), quality of life, functional health status and clinical outcomes (eg, days hospitalised). Study implementation, acceptability, feasibility, costs and potential cost-effectiveness will also be evaluated. ETHICS AND DISSEMINATION: The University of Pennsylvania Review Board has approved the study as the single IRB of record (protocol # 849575, V.1.4). Results will be published in peer-reviewed journals and summaries will be provided to study funders. TRIAL REGISTRATION NUMBER: NCT05260268.

Physician Preferences when Selecting Candidates for Lower-Quality Kidney Offers.

BACKGROUND: In the United States, more than 50% of kidneys in the lowest 15% quality range (those with Kidney Donor Profile Index >85) are discarded. Studies suggest that using more of these kidneys could benefit patients waiting for a transplant. This study assesses the trade-offs physicians make when selecting recipients for lower-quality kidneys. METHODS: A discrete choice experiment (DCE) was administered to surgeons and nephrologists in the United States who are involved in kidney acceptance decisions. The DCE presented kidneys that varied in terms of Kidney Donor Profile Index, expected cold ischemia time, donor age, pump parameters, serum creatinine levels, glomerulosclerosis, donor diabetes status, and whether donation was made after circulatory death. Candidate characteristics included recipients' age, diabetes history, time on dialysis, ejection fraction, HLA mismatch, calculated panel reactive antibody, and Karnofsky performance score. Regression analysis was used to estimate acceptability weights associated with kidney and recipient characteristics. RESULTS: A total of 108 physicians completed the DCE. The likelihood of acceptance was significantly lower with deterioration of kidney quality, expected cold ischemia time at transplantation, and missing biopsy and pump information. Acceptance was prioritized for patients who were higher on the waiting list, younger recipients, those who have spent less time on dialysis, and those without a history of diabetes. Performance status (Karnofsky score) and calculated panel reactive antibody also had a statistically significant but smaller association. Finally, ejection fraction had a marginally significant association, and HLA match had no significant association with the acceptance of marginal kidneys. A group of respondents were found to be primarily concerned about cold ischemia time. CONCLUSIONS: In this DCE, physicians considered the recipient characteristics that inform expected post-transplant survival score when they decided whether to accept a marginal kidney for a given recipient.

Association of Frailty With Health-Related Quality of Life in Liver Transplant Recipients.

Importance: Frailty has been recognized as a risk factor for mortality after liver transplant (LT) but little is known of its association with functional status and health-related quality of life (HRQL), termed global functional health, in LT recipients. Objective: To evaluate the association between pre-LT and post-LT frailty with post-LT global functional health. Design, Setting, and Participants: This prospective cohort study was conducted at 8 US LT centers and included adults who underwent LT from October 2016 to February 2020. Exposures: Frail was defined by a pre-LT Liver Frailty Index (LFI) score of 4.5 or greater. Main Outcomes and Measures: Global functional health at 1 year after LT, assessed using surveys (Short Form-36 [SF-36; summarized by physical component scores (PFC) and mental component summary scores (MCS)], Instrumental Activities of Daily Living scale) and performance-based tests (LFI, Fried Frailty Phenotype, and Short Physical Performance Battery). Results: Of 358 LT recipients (median [IQR] age, 60 [53-65] years; 115 women [32%]; 25 [7%] Asian/Pacific Islander, 21 [6%] Black, 54 [15%] Hispanic White, and 243 [68%] non-Hispanic White individuals), 68 (19%) had frailty pre-LT. At 1 year post-LT, the median (IQR) PCS was lower in recipients who had frailty vs those without frailty pre-LT (42 [31-53] vs 50 [38-56]; P = .002), but the median MCS was similar. In multivariable regression, pre-LT frailty was associated with a -5.3-unit lower post-LT PCS (P < .001), but not MCS. The proportion who had difficulty with 1 or more Instrumental Activities of Daily Living (21% vs 10%) or who were unemployed/receiving disability (38% vs 29%) was higher in recipients with vs without frailty. In a subgroup of 210 recipients with LFI assessments 1 year post-LT, 13% had frailty at 1 year post-LT. Recipients who had frailty post-LT reported lower adjusted SF-36-PCS scores (coefficient, -11.4; P < .001) but not SF-36-MCS scores. Recipients of LT who had frailty vs those without frailty 1 year post-LT also had worse median (IQR) Fried Frailty Phenotype scores (1 [1-2] vs 1 [0-1]) and higher rates of functional impairment by a Short Physical Performance Battery of 9 or less (42% vs 20%; P = .01). Conclusions and Relevance: In this cohort study, pre-LT frailty was associated with worse global functional health 1 year after LT. The presence of frailty after LT was also associated with worse HRQL in physical, but not mental, subdomains. These data suggest that interventions and therapeutics that target frailty that are administered before and/or early post-LT may help to improve the health and well-being of LT recipients.

The Role of Procurement Biopsies in Kidney Acceptance Decision Making and Kidney Discard: Perceptions of Physicians, Nurse Coordinators, and OPO Staff and Directors.

Procurement biopsies suffer from challenges with quality and reproducibility and are linked to kidney discard. Nonetheless, procurement biopsies are obtained for the majority of kidneys in the United States, and biopsy findings are commonly relied upon in kidney acceptance decisions. Methods: We conducted in-depth, semistructured interviews with 30 surgeons, nephrologists, nurse coordinators, and organ procurement organization (OPO) staff and directors to assess perceptions of factors contributing to kidney discard and strategies to reduce kidney discard, with a focus on the role of procurement biopsies. Thematic analysis was used to analyze qualitative data. Results: Three main themes emerged: (1) participants emphasized the importance of biopsy findings in making acceptance decisions but expressed concerns about a lack of standardization and quality control; (2) participants reported large variations in the level of importance placed on biopsy findings, the level of reliance on glomerulosclerosis in particular, and the cutoffs used; and (3) participants disagreed about how often procurement biopsies should be taken, with some supporting stricter limits on which kidneys are biopsied and others preferring a biopsy for most kidney offers. Conclusions: These findings support the development of standard practices for which kidneys require biopsy, how the biopsy material is prepared, and how the biopsy is interpreted. Variability in kidney acceptance practices across centers and the use of biopsy findings in guiding recipient selection also lend support to policies to allocate kidneys with suboptimal histological findings to the centers that are willing to use such kidneys and the patients who could most benefit from such offers.

Frailty, mortality, and health care utilization after liver transplantation: From the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study.

BACKGROUND AND AIMS: Frailty is a well-established risk factor for poor outcomes in patients with cirrhosis awaiting liver transplantation (LT), but whether it predicts outcomes among those who have undergone LT is unknown. APPROACH AND RESULTS: Adult LT recipients from 8 US centers (2012-2019) were included. Pre-LT frailty was assessed in the ambulatory setting using the Liver Frailty Index (LFI). "Frail" was defined by an optimal cut point of LFI ≥ 4.5. We used the 75th percentile to define "prolonged" post-LT length of stay (LOS; ≥12 days), intensive care unit (ICU) days (≥4 days), and inpatient days within 90 post-LT days (≥17 days). Of 1166 LT recipients, 21% were frail pre-LT. Cumulative incidence of death at 1 and 5 years was 6% and 16% for frail and 4% and 10% for nonfrail patients (overall log-rank p = 0.02). Pre-LT frailty was associated with an unadjusted 62% increased risk of post-LT mortality (95% CI, 1.08-2.44); after adjustment for body mass index, HCC, donor age, and donation after cardiac death status, the HR was 2.13 (95% CI, 1.39-3.26). Patients who were frail versus nonfrail experienced a higher adjusted odds of prolonged LT LOS (OR, 2.00; 95% CI, 1.47-2.73), ICU stay (OR, 1.56; 95% CI, 1.12-2.14), inpatient days within 90 post-LT days (OR, 1.72; 95% CI, 1.25-2.37), and nonhome discharge (OR, 2.50; 95% CI, 1.58-3.97). CONCLUSIONS: Compared with nonfrail patients, frail LT recipients had a higher risk of post-LT death and greater post-LT health care utilization, although overall post-LT survival was acceptable. These data lay the foundation to investigate whether targeting pre-LT frailty will improve post-LT outcomes and reduce resource utilization.

Frailty and the Risk of Acute Kidney Injury Among Patients With Cirrhosis.

Acute kidney injury (AKI) and frailty are major drivers of outcomes among patients with cirrhosis. What is unknown is the impact of physical frailty on the development of AKI. We included adults with cirrhosis without hepatocellular carcinoma listed for liver transplantation at nine US centers (n = 1,033). Frailty was assessed using the Liver Frailty Index (LFI); "frail" was defined by LFI ≥ 4.2. Chronic kidney disease as a baseline estimated glomerular filtration rate <60 mL/min/1.73 m2 . Our primary outcome, AKI, was defined as an increase in serum creatinine ≥0.3 mg/dL or a serum creatinine ≥1.5-fold increase. Wait-list mortality was defined as either a death on the wait list or removal for being too sick. We performed Cox regression analyses to estimate the hazard ratios (HRs) for AKI and wait-list mortality. Of 1,033 participants, 41% were frail and 23% had CKD. Twenty-one percent had an episode of AKI during follow-up. Frail versus nonfrail patients were more likely to develop AKI (25% vs. 19%) and wait-list mortality (21% vs. 13%) (P < 0.01 for each). In multivariable Cox regression, each of the following groups was associated with a higher risk of AKI as compared with not frail/no CKD: frail/no CKD (adjusted HR [aHR] = 1.87, 95% confidence interval [CI] = 1.29-2.72); not frail/CKD (aHR = 4.30, CI = 2.88-6.42); and frail/CKD (aHR = 4.85, CI = 3.33-7.07). We use a readily available metric, LFI, to identify those patients with cirrhosis most at risk for AKI. We highlight that serum creatinine and creatinine-based estimations of glomerular filtration rate may not fully capture a patient's vulnerability to AKI among the frail phenotype. Conclusion: Our work lays the foundation for implementing physical frailty in clinical practice to identify AKI earlier, implement reno-protective strategies, and expedite liver transplantation.

Association of Frailty and Sex With Wait List Mortality in Liver Transplant Candidates in the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study.

Importance: Female liver transplant candidates experience higher rates of wait list mortality than male candidates. Frailty is a critical determinant of mortality in patients with cirrhosis, but how frailty differs between women and men is unknown. Objective: To determine whether frailty is associated with the gap between women and men in mortality among patients with cirrhosis awaiting liver transplantation. Design, Setting, and Participants: This prospective cohort study enrolled 1405 adults with cirrhosis awaiting liver transplant without hepatocellular carcinoma seen during 3436 ambulatory clinic visits at 9 US liver transplant centers. Data were collected from January 1, 2012, to October 1, 2019, and analyzed from August 30, 2019, to October 30, 2020. Exposures: At outpatient evaluation, the Liver Frailty Index (LFI) score was calculated (grip strength, chair stands, and balance). Main Outcomes and Measures: The risk of wait list mortality was quantified using Cox proportional hazards regression by frailty. Mediation analysis was used to quantify the contribution of frailty to the gap in wait list mortality between women and men. Results: Of 1405 participants, 578 (41%) were women and 827 (59%) were men (median age, 58 [interquartile range (IQR), 50-63] years). Women and men had similar median scores on the laboratory-based Model for End-stage Liver Disease incorporating sodium levels (MELDNa) (women, 18 [IQR, 14-23]; men, 18 [IQR, 15-22]), but baseline LFI was higher in women (mean [SD], 4.12 [0.85] vs 4.00 [0.82]; P = .005). Women displayed worse balance of less than 30 seconds (145 [25%] vs 149 [18%]; P = .003), worse sex-adjusted grip (mean [SD], -0.31 [1.08] vs -0.16 [1.08] kg; P = .01), and fewer chair stands per second (median, 0.35 [IQR, 0.23-0.46] vs 0.37 [IQR, 0.25-0.49]; P = .04). In unadjusted mixed-effects models, LFI was 0.15 (95% CI, 0.06-0.23) units higher in women than men (P = .001). After adjustment for other variables associated with frailty, LFI was 0.16 (95% CI, 0.08-0.23) units higher in women than men (P < .001). In unadjusted regression, women experienced a 34% (95% CI, 3%-74%) increased risk of wait list mortality than men (P = .03). Sequential covariable adjustment did not alter the association between sex and wait list mortality; however, adjustment for LFI attenuated the mortality gap between women and men. In mediation analysis, an estimated 13.0% (IQR, 0.5%-132.0%) of the gender gap in wait list mortality was mediated by frailty. Conclusions and Relevance: These findings demonstrate that women with cirrhosis display worse frailty scores than men despite similar MELDNa scores. The higher risk of wait list mortality that women experienced appeared to be explained in part by frailty.

Safety and Efficacy of Segmental Yttrium-90 Radioembolization for Hepatocellular Carcinoma after Transjugular Intrahepatic Portosystemic Shunt Creation.

PURPOSE: To evaluate safety and efficacy of segmental yttrium-90 (Y90) radioembolization for hepatocellular carcinoma (HCC) after transjugular intrahepatic portosystemic shunt (TIPS) placement. The hypothesis was liver sparing segmental Y90 for HCC after TIPS would provide high antitumor response with a tolerable safety profile. MATERIALS AND METHODS: This single-arm retrospective study included 39 patients (16 women, 23 men) with ages 49-81 years old who were treated with Y90. Child-Pugh A/B liver dysfunction was present in 72% (28/39) with a median Model for End-stage Liver Disease score of 18 (95% confidence interval, 16.4-19.4). Primary outcomes were clinical and biochemical toxicities and antitumor imaging response by World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria. Secondary outcomes were orthotopic liver transplantation (OLT), time to progression (TTP), and overall survival (OS) estimates by the Kaplan-Meier method. RESULTS: The 30-day mortality was 0%. Grade 3+ clinical adverse events and grade 3+ hyperbilirubinemia occurred in 5% (2/39) and 0% (0/39), respectively. Imaging response was achieved in 58% (22/38, WHO criteria) and 74% (28/38, EASL criteria), respectively. Median TTP was 16.1 months for any cause and 27.5 months for primary index lesions. OLT was completed in 88% (21/24) of listed patients at a median time of 6.1 months (range, 0.9-11.7 months). Median OS was 31.6 months and 62.9 months censored and uncensored to OLT, respectively. CONCLUSIONS: Segmental Y90 for HCC appears safe and efficacious in patients after TIPS. Preserved transplant eligibility suggests that Y90 is a useful tool for bridging these patients to liver transplantation.

Liver Transplantation Following Yttrium-90 Radioembolization: 15-Year Experience in 207-Patient Cohort.

BACKGROUND AND AIMS: Radioembolization (yttrium-90 [Y90]) is used in hepatocellular carcinoma (HCC) as a bridging as well as downstaging liver-directed therapy to curative liver transplantation (LT). In this study, we report long-term outcomes of LT for patients with HCC who were bridged/downstaged by Y90. APPROACH AND RESULTS: Patients undergoing LT following Y90 between 2004 and 2018 were included, with staging by United Network for Organ Sharing (UNOS) tumor-node-metastasis criteria at baseline pre-Y90 and pre-LT. Post-Y90 toxicities were recorded. Histopathological data of HCC at explant were recorded. Long-term outcomes, including overall survival (OS), recurrence-free survival (RFS), disease-specific mortality (DSM), and time-to-recurrence, were reported. Time-to-endpoint analyses were estimated using Kaplan-Meier. Univariate and multivariate analyses were performed using a log-rank test and Cox proportional-hazards model, respectively. During the 15-year period, 207 patients underwent LT after Y90. OS from LT was 12.5 years, with a median time to LT of 7.5 months [interquartile range, 4.4-10.3]. A total of 169 patients were bridged, whereas 38 were downstaged to LT. Respectively, 94 (45%), 60 (29%), and 53 (26%) patients showed complete, extensive, and partial tumor necrosis on histopathology. Three-year, 5-year, and 10-year OS rates were 84%, 77%, and 60%, respectively. Twenty-four patients developed recurrence, with a median RFS of 120 (95% confidence interval, 69-150) months. DSM at 3, 5, and 10 years was 6%, 11%, and 16%, respectively. There were no differences in OS/RFS for patients who were bridged or downstaged. RFS was higher in patients with complete/extensive versus partial tumor necrosis (P < 0.0001). For patients with UNOS T2 treated during the study period, 5.2% dropped out because of disease progression. CONCLUSIONS: Y90 is an effective treatment for HCC in the setting of bridging/downstaging to LT. Patients who achieved extensive or complete necrosis had better RFS, supporting the practice of neoadjuvant treatment before LT.

Neuropraxia: An Underappreciated Morbidity of Liver Transplantation.

BACKGROUND: Peripheral nerve injuries can be devastating complications of surgery, potentially resulting in severe functional disability and decreased quality of life. Long surgeries with considerable tissue manipulation, for example, liver transplantation, may present increased risk; however, neuropraxia in transplantation has not been well investigated. MATERIALS AND METHODS: This is a retrospective study of all adult patients undergoing liver transplantation at a large academic center between January 2013 and December 2015. Descriptive analyses, logistic regressions, and forward selection procedures were used to determine the odds of developing neuropraxia and associated factors. RESULTS: Of the 283 liver recipients, the mean age was 55.8 y, 35.1% were female, 65.6% were Caucasian, 8.9% were African American, 16.7% were Hispanic, and mean model for end-stage liver disease sodium score at transplant was 24.2 ± 10.9. The underlying etiology was alcohol (26.2%), hepatitis C (34.8%), nonalcoholic steatohepatitis (13.1%), and other (14.2%). The incidence of neuropraxia after liver transplantation was 8.3% (n = 25), with 60% (n = 16) upper extremities, 82% left sided, and 84% male. There was no difference in age, race, body mass index, hypertension, diabetes, hyperlipidemia, or smoking in those with neuropraxia versus those without. In multivariate analysis, neuropraxia was significantly associated with male gender, lower model for end-stage liver disease score, and longer duration of surgery (P < 0.05). Symptoms lasted median 5 d, with a wide range up to 187 d. Neuropraxia-specific treatment (physical therapy or medications) was required in 32% (n = 9). CONCLUSIONS: Peripheral nerve injuries are an unexplored complication of liver transplantation. Although transient, a high number (8.2%) of patients developed neuropraxia, negatively affecting their ability for recovery. Exploration of mechanisms for minimizing risk and intraoperative detection and prevention should be considered to mitigate this complication.

Trends and predictors of multidimensional health-related quality of life after living donor kidney transplantation.

PURPOSE: Living donor kidney transplant (LDKT) imparts the best graft and patient survival for most end-stage kidney disease (ESKD) patients. Yet, there remains variation in post-LDKT health-related quality of life (HRQOL). Improved understanding of post-LDKT HRQOL can help identify patients for interventions to maximize the benefit of LDKT. METHODS: For 477 LDKT recipients transplanted between 11/2007 and 08/2016, we assessed physical, mental, social, and kidney-targeted HRQOL pre-LDKT, as well as 3 and 12 months post-operatively using the SF-36, Kidney Disease Quality of Life-Short Form (KDQOL-SF), and the Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 item version (FKSI-19). We then examined trajectories of each HRQOL domain using latent growth curve models (LGCMs). We also examined associations between decline in HRQOL from 3 months to 12 months post-LDKT and death censored graft failure (DCGF) using Cox regression. RESULTS: Large magnitude effects (d > 0.80) were observed from pre- to post-LDKT change on the SF-36 Vitality scale (d = 0.81) and the KDQOL-SF Burden of Kidney Disease (d = 1.05). Older age and smaller pre- to post-LDKT decreases in serum creatinine were associated with smaller improvements on many HRQOL scales across all domains in LGCMs. Higher DCGF rates were associated with worse physical [e.g., SF-36 PCSoblique hazard ratio (HR) 1.18; 95% CI 1.01-1.38], mental (KDQOL-SF Cognitive Function HR 1.27; 95% CI 1.00-1.62), and kidney-targeted (FKSI-19 HR: 1.18; 95% CI 1.00-1.38) HRQOL domains. CONCLUSION: Clinical HRQOL monitoring may help identify patients who are most likely to have failing grafts and who would benefit from post-LDKT intervention.

Patients With Persistently Low MELD-Na Scores Continue to Be at Risk of Liver-related Death.

BACKGROUND: The vast majority of patients with cirrhosis have low Model for End-Stage Liver Disease-Sodium (MELD-Na) scores; however, the ability for the MELD-Na score to predict patient outcomes at low scores is unclear. METHODS: Adult patients in a multicenter, Chicago-wide database of medical records with International Classification of Disease, Ninth Edition codes of cirrhosis and without a history of hepatocellular carcinoma were included. Records were linked with the state death registry, and death certificates were manually reviewed. Deaths were classified as "liver-related," "non-liver-related," and "non-descript" as adjudicated by a panel comprised of a transplant surgeon, a hepatologist, and an internist. A sensitivity analysis was performed where patients with hepatocellular carcinoma were included. RESULTS: Among 7922 identified patients, 3999 patients had MELD-Na scores that were never higher than 15. In total, 2137 (27%) patients died during the study period with higher mortality rates for the patients in the high MELD-Na group (19.4 (41.6%) versus 4.1 (12.6%) per 100 person-y, P < 0.001). The high MELD-Na group died of a liver-related cause in 1142 out of 1632 (70%) as compared to 240 out of 505 (47.5%) deaths in the low MELD-Na group. There was no difference in the distribution of subcategory of liver-related death between low and high MELD-Na groups. Among subclassification of liver-related deaths, the most common cause of death was "Infectious" in both groups. CONCLUSIONS: Despite persistently low MELD-Na scores, patients with cirrhosis still experience high rates of liver-related mortality.

Real-World Study of Once-Daily, Extended-Release Tacrolimus Versus Twice-Daily, Immediate-Release Tacrolimus in Kidney Transplantation: Clinical Outcomes and Healthcare Resource Utilization.

INTRODUCTION: Real-world data with extended-release tacrolimus (ER-T) are lacking in the USA. This study examined clinical outcomes and healthcare resource utilization in kidney transplant patients receiving ER-T in clinical practice. METHODS: This was a retrospective, single-center analysis (February-June 2016) using data from Northwestern University's Enterprise Data Warehouse. Adult patients receiving a kidney transplant in the preceding 4 years, treated de novo or converted to ER-T from immediate-release tacrolimus (IR-T) within 10 days post-transplantation, and maintained on ER-T (at least 3 months) were included. Patients were matched for demographic and clinical characteristics with IR-T-treated control patients. Endpoints included clinical outcomes and healthcare resource utilization up to 1 year post-transplantation. RESULTS: A total of 19 ER-T-treated patients were matched with 55 IR-T-treated patients. No ER-T-treated patients experienced biopsy-confirmed acute rejection (BCAR) or graft failure versus 3 (5.5%) and 3 (5.5%) IR-T-treated patients, respectively. Mean estimated glomerular filtration rate (eGFR), the number of all-cause outpatient visits, readmissions, and all-cause hospitalization days were comparable between groups. Tacrolimus trough levels, days to target level (6-10 ng/mL), and number of required dose adjustments were also similar. CONCLUSION: Real-world clinical outcomes and healthcare resource utilization were similar with ER-T and IR-T. Larger studies will need to investigate the trend toward fewer BCAR events, and increased graft survival with ER-T. FUNDING: Astellas Pharma Global Development, Inc. Plain language summary available for this article.

Deceased organ donor screening for human immunodeficiency virus, hepatitis B virus and hepatitis C virus: Discordant serology and nucleic acid testing results.

BACKGROUND: Before the 2014 policy change pertaining to infectious disease screening, many organ procurement organizations (OPOs) were supplementing serologic screening of deceased organ donors with nucleic acid testing (NAT) for human immunodeficiency virus (HIV-1), hepatitis B virus (HBV), and hepatitis C virus (HCV). The number of seronegative, NAT-positive donors has not been directly measured. METHODS: HIV, HBV, and HCV screening results of 11 229 donor referrals evaluated from 2010 to 2013 were obtained from 3 OPO-affiliated laboratories, capturing 35% of all donors in the United States. Laboratories used either polymerase chain reaction assay or transcription-mediated amplification assay to test 9643 deceased donors by NAT. RESULTS: The NAT results were positive in 21 (0.2%), 1 (0.02%), and 11 (0.1%) donors who were seronegative for HIV, HBV, and HCV, respectively. All discordant HIV-1 results were from one laboratory using a polymrease chain reaction assay. Thirteen of the reactive HIV NAT results in seronegative referrals were repeated and were non-reproducibly positive (NRP). Ten (0.1%), 452 (7.8%), and 197 (2.2%) of HIV-, HBV-, and HCV-seropositive donors, respectively, were negative by NAT. CONCLUSIONS: This study highlights the importance of robust quality assurance to minimize NRP NAT results. NAT may allow for increased utilization of organs from HBV- and HCV-seropositive, NAT-negative donors.