Implications of drug intoxication on donor utilization and outcomes in liver transplantation.

INTRODUCTION: This study evaluates the implications of drug intoxication (DI) on donor utilization and outcomes in liver transplantation (LT). METHODS: The UNOS STAR database was evaluated for all potential donors and adult, first-time, whole LT between 2005 and 2019. Logistic regression analyses evaluated liver utilization; proportional hazards modeling assessed risk of 1-year graft loss. RESULTS: A total of 132 783 potential donors (10 205, 7.7% from DI), and 90 612 adult LT were identified (7490, 8.3% from DI). DI donors had median age 32 years (IQR 26-40 years, p < .001), were 42.6% female (n = 4346), and 15.5% were DCD donors (n = 1583). Utilization of DI donors changed over time, such that by 2015-2019 they were the most likely donor cause of death (COD) to be utilized. Among LT recipients, there were insignificant differences (<2% variance) in age, gender, ethnicity, and etiology of liver disease according to donor COD. Recipients with MELD scores >30 more frequently received grafts from donors with trauma (23.8%) and DI (21.8%) versus cardiovascular (20.0%) and CVA/stroke (19.9%, p < .001). Among DBD donors, DI-COD was associated with superior 1-year graft survival compared to donors from trauma (HR 1.172, 95% CI 1.057-1.300) and CVA/stroke (HR 1.404, 95% CI 1.264-1.561, p < .001). Donor COD was not significantly associated with 1-year graft loss among DCD donors. CONCLUSIONS: There is an increased likelihood of donor utilization when COD is drug overdose and an increased likelihood of 1-year graft survival compared to donors from trauma, CVA/stroke, and other COD.

Incidence and Outcomes of Simultaneous Thoracoabdominal Triple Organ Transplantation in the United States.

BACKGROUND: This study aims to evaluate patient outcomes of simultaneous triple organ transplants, which may provide insight into optimal donor allocation while maximizing recipient benefit. METHODS: Triple organ transplants and their corollary dual organ transplants were identified using the United Network for Organ Sharing database. Triple organ transplants evaluated included heart-lung-kidney (n = 12) and heart-liver-kidney (n = 37). Heart-lung-kidney recipients were compared with heart-lung (n = 325), lung-kidney (n = 91), and heart-kidney (n = 2022) groups. Heart-liver-kidney recipients were compared with heart-liver (n = 451), liver-kidney (n = 10422), and heart-kidney (n = 2517) recipients. Patient survival outcomes were calculated using the Kaplan-Meier method and compared using log-rank tests. RESULTS: Patients undergoing triple organ transplants showed similar 10-year survival as their corresponding dual organ transplant cohorts. Patient survival estimate at 10 years for the heart-lung-kidney group was 45%, with no statistically significant difference in survival when compared with dual organ groups (P = .16). Survival estimates at 10 years for the heart-liver-kidney group was 49%, with no statistically significant difference in survival when compared with dual organ groups (P = .06). CONCLUSION: Despite the surgical burden of adding a third organ transplant, heart-liver-kidney and heart-lung-kidney have similar survival outcomes to dual organ equivalents and represent a reasonable allocation option in well-selected patients.

Preserved 2-y Liver Transplant Outcomes Following Simultaneous Thoracoabdominal DCD Organ Procurement Despite Effects on Liver Utilization Rate.

Background: Current techniques for donation after circulatory determination of death (DCD) heart procurement, through either direct procurement and machine perfusion or thoracoabdominal normothermic regional perfusion (NRP), have demonstrated excellent heart transplant outcomes. However, the impact of thoracoabdominal DCD (TA-DCD) heart procurement on liver allograft outcomes and utilization is poorly understood. Methods: One hundred sixty simultaneous heart and liver DCD donors were identified using the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between December 2019 and July 2021. Liver outcomes from TA-DCD donors were stratified by heart procurement technique and evaluated for organ utilization, graft survival, and patient survival. Results were compared with abdominal-only DCD (A-DCD; n = 1332) and donation after brain death (DBD; n = 12 891) liver transplants during the study interval. Kaplan-Meier methods with log-rank testing were used to evaluate patient and graft survival. Results: One hundred thirty-three of 160 livers procured from TA-DCD donors proceeded to transplant. TA-DCD donors were younger (mean 28.26 y; P < 0.0001) with lower body mass index (mean 26.61; P < 0.0001) than A-DCD and DBD donors. TA-DCD livers had equivalent patient survival ( P = 0.893) and superior graft survival (P = 0.009) compared with A-DCD. TA-DCD livers had higher rates of organ discard for long warm ischemia time (37.0%) than A-DCD (20.5%) and DBD (0.5%; P < 0.0001), with direct procurement and machine perfusion procurements leading to a higher discard rate (18.5%) than NRP procurements (7.4%). Conclusions: Liver transplants after TA-DCD donation demonstrated equivalent patient outcomes and excellent graft outcomes. NRP procurements resulted in the lowest rate of organ discard after DCD donation and may represent an optimal strategy to maximize organ utilization.

Robotic bilateral nephrectomy for large polycystic kidney disease.

Objective: This study aims to describe our technique and review our experience with synchronous robotic bilateral nephrectomy for large kidneys in ADPKD with the da Vinci XI and da Vinci Single Port platforms (Intuitive Surgical, Sunnyvale, CA). Materials and Methods: We performed a retrospective review of all robotic bilateral nephrectomy cases from January 2020 to present at a high-volume robotic single centre. Demographic data and perioperative details including preoperative CT scans, indication for nephrectomy and renal function were collected. We also collected post-op course data and final specimen data details. Results: Fourteen cases were included. Patient demographics, indications for surgery and specimen data are outlined in Table 1. The largest kidney removed has a measurement of 32 cm in the largest dimension on preoperative imaging. Median operating time from incision to closure was 299 min (IQR 260, 339). Median estimated blood loss was 75 cc (IQR 50, 187.5). Two patients were transfused intraoperatively. Median pre- and post-operative Hgb was 11.0 and 9.6, respectively. Median length of stay was 3 days (IQR 2, 3.5). There were no intraoperative complications and no open conversions. Post-operative complications included one incisional hematoma and one superficial wound infection. One patient was admitted to the surgical ICU post operatively for ventilatory support. Two patients were readmitted within 30 days of surgery. Conclusion: The robotic approach to bilateral native nephrectomy for ADPKD should be considered when native nephrectomies are indicated. The operative times and outcomes are favourable compared with prior series, and this technique works even for very large kidneys.

Drug Overdose and Cardiovascular Deaths Among Deceased Organ Donors: Implications for Donor Utilization and Data Reporting.

BACKGROUND The present study evaluated expanded cause of death (COD) definitions and its implications on donor utilization for solid organ transplantation. MATERIAL AND METHODS The OPTN Standard Transplant and Research file was queried for potential donors between 2005 and 2019. Donor- and organ-specific utilization were evaluated. Expanded donor COD were identified: trauma, cardiovascular (CV), cerebrovascular accident (CVA) or stroke, drug intoxication (DI), anoxia not otherwise specified (NOS), and other. Descriptive analyses and multivariable logistic regression analyses for donor utilization were performed. RESULTS Among 132 783 potential donors identified, the most common COD was CVA/Stroke (n=44 707, 33.7%), followed by trauma (n=43 356, 32.7%), CV (n=20 053, 15.1%), anoxia-NOS (n=12 261, 9.2%), DI (n=10 205, 7.7%), and other causes (n=2201, 1.7%). Significant differences between CV, DI, and anoxia-NOS groups existed for donor age, sex, ethnicity, body mass index, and comorbidities. Donors from trauma had the highest unadjusted utilization rate (97.2%) while CV donors had the lowest (90.1%). Multivariable analysis of brain-dead donors (DBD) showed that compared to trauma, donors from DI had higher likelihood of utilization (odds ratio 1.217, 95% 1.025-1.446) while CV donors were lower (OR 0.717, 95% CI 0.642-0.800, P<0.001). Among donation after circulatory death (DCD) donors, there was decreased utilization compared to trauma for both CV (OR 0.607, 95% CI 0.523-0.705) and DI (OR 0.754, 95% CI 0.603-0.914, P<0.001). CONCLUSIONS Current COD definitions should be expanded to capture significant differences in the donor population. DI donors are the fastest growing cohort and the most likely utilized DBD donors, while trauma donors remain the most likely utilized DCD donors.

A Retrospective Evaluation of Changing Health Characteristics Amongst Deceased Organ Donors in the United States.

BACKGROUND: The availability of suitable donor organs remains a limiting factor to performing life-saving transplant operations. This study evaluates changes in the health of the donor population and its influence on organ use in the United States. METHODS: A retrospective analysis was performed using the OPTN STAR data file from 2005 to 2019. Three donor eras were defined: 1) 2005 to 2009, 2) 2010 to 2014, and 3) 2015 to 2019. The primary outcome was donor use, defined as transplantation of at least one solid organ. Descriptive analyses were performed, and associations of donor use were examined with multivariable logistic regression models. P values <.01 were considered significant. RESULTS: The cohort included 132,783 potential donors of which 124,729 (93.9%) were used for transplantation. Donor median age was 42 years (interquartile range 26-54), 53,566 (40.3%) were female, and 88,209 (66.4%) were White, 21,834 (16.4%) were black, and 18,509 (13.9%) were Hispanic. Compared with donors from Eras 1 and 2, donors in Era 3 were younger (P < .001), had higher body mass index (BMI) (P < .001), increased rates of diabetes mellitus (DM) (P < .001), hepatitis C virus (HCV) positivity (P < .001) and more comorbidities (P < .001). Multivariable modeling found donor BMI, DM, hypertension, and HCV status as health factors significantly associated with donor use. Compared with Era 1, there was increased use in Era 3 of donors with BMI ≥30 kg/m2, DM, hypertension, HCV-positive status, and donors with ≥3 comorbidities. CONCLUSIONS: Despite an increasing prevalence of chronic health problems in the donor population, donors with multiple comorbid conditions are more likely to be used for transplantation in recent years.

HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma.

BACKGROUND AND AIMS: The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC. APPROACH AND RESULTS: Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n  = 106) and an independent validation cohort ( n  = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99). CONCLUSION: HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.

Machine learning models are superior to noninvasive tests in identifying clinically significant stages of NAFLD and NAFLD-related cirrhosis.

BACKGROUND AND AIMS: We assessed the performance of machine learning (ML) models in identifying clinically significant NAFLD-associated liver fibrosis and cirrhosis. APPROACH AND RESULTS: We implemented ML models including logistic regression (LR), random forest (RF), and artificial neural network to predict histological stages of fibrosis using 17 demographic/clinical features in 1370 patients with NAFLD who underwent liver biopsy, FibroScan, and labs within a 6-month period at multiple U.S. centers. Histological stages of fibrosis (≥F2, ≥F3, and F4) were predicted using ML, FibroScan liver stiffness measurements, and Fibrosis-4 index (FIB-4). NASH with significant fibrosis (NAS ≥ 4 + ≥F2) was assessed using ML, FibroScan-AST (FAST) score, FIB-4, and NAFLD fibrosis score (NFS). We used 80% of the cohort to train and 20% to test the ML models. For ≥F2, ≥F3, F4, and NASH + NAS ≥ 4 + ≥F2, all ML models, especially RF, had primarily higher accuracy and AUC compared with FibroScan, FIB-4, FAST, and NFS. AUC for RF versus FibroScan and FIB-4 for ≥F2, ≥F3, and F4 were (0.86 vs. 0.81, 0.78), (0.89 vs. 0.83, 0.82), and (0.89 vs. 0.86, 0.85), respectively. AUC for RF versus FAST, FIB-4, and NFS for NASH + NAS ≥ 4 + ≥F2 were (0.80 vs. 0.77, 0.66, 0.63). For NASH + NAS ≥ 4 + ≥F2, all ML models had lower/similar percentages within the indeterminate zone compared with FIB-4 and NFS. Overall, ML models performed better in sensitivity, specificity, positive predictive value, and negative predictive value compared with traditional noninvasive tests. CONCLUSIONS: ML models performed better overall than FibroScan, FIB-4, FAST, and NFS. ML could be an effective tool for identifying clinically significant liver fibrosis and cirrhosis in patients with NAFLD.

Disparities in curative treatments and outcomes for early stage intrahepatic cholangiocarcinoma in the United States.

BACKGROUND: Curative surgical treatments afford the best prognosis for patients with intrahepatic cholangiocarcinoma (iCCA); however, the comparative effectiveness of treatment options and factors associated with curative treatment receipt for early stage iCCA remain unknown. METHODS: The authors identified patients who were diagnosed with early stage iCCA, defined as a unifocal tumor <3 cm, during 2004-2018 from the National Cancer Database. Multivariable logistic and Cox regression analyses were used to identify the factors associated with curative treatment and overall survival (OS), respectively. RESULTS: The proportion of patients with early stage iCCA increased from 4.5% in 2004 to 7.3% in 2018, with the odds of early stage detection increasing by 3.1% per year (odds ratio [OR], 1.031; 95% CI, 1.015-1.049). Of 1093 patients who had early stage iCCA, 464 (42.5%) underwent resection, 113 (10.3%) underwent ablation, 62 (5.7%) underwent liver transplantation, and 454 (41.5%) received noncurative treatments. Hispanic patients (adjusted OR [aOR], 0.57; 95% CI, 0.33-0.97) and Black patients (aOR, 0.47; 95% CI, 0.28-0.77) were less likely to receive curative treatments than White patients. Compared with patients who underwent surgical resection, those who underwent liver transplantation had a trend toward improved OS (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.37-1.08), whereas those who underwent local ablation (aHR, 1.39; 95% CI, 1.01-1.92) and noncurative treatments (aHR, 3.97; 95% CI, 3.24-4.88) experienced worse OS. CONCLUSIONS: More than one third of patients with early stage iCCA did not receive curative treatment, with Hispanic and Black patients being less likely to receive curative treatments than White patients. Surgical resection and liver transplantation were associated with improved survival compared with local ablation. Future studies should investigate disparities in curative treatment receipt and outcomes for early stage iCCA.

Long term tolerability and clinical outcomes associated with tocilizumab in the treatment of refractory antibody mediated rejection (AMR) in pediatric renal transplant recipients.

BACKGROUND: Treatment options for antibody-mediated rejection (AMR) are limited. Recent studies have shown that inhibition of interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R) signaling can reduce inflammation and slow AMR progression. METHODS: We report our experience using monthly tocilizumab (anti-IL6R) in 25 pediatric renal transplant recipients with AMR, refractory to IVIg/Rituximab. From January 2013 to June 2019, a median (IQR) of 12 (6.019.0) doses of tocilizumab were given per patient. Serial assessments of renal function, biopsy findings, and HLA DSA (by immunodominant HLA DSA [iDSA] and relative intensity score [RIS]) were performed. RESULTS: Median (IQR) time from transplant to AMR was 41.4 (24.367.7) months, and time from AMR to first tocilizumab was 10.6 (8.317.6) months. At median (IQR) follow up of 15.8 (8.435.7) months post-tocilizumab initiation, renal function was stable except for 1 allograft loss. There was no significant decrease in iDSA or RIS. Follow up biopsies showed reduction in peritubular capillaritis (p = .015) and C4d scoring (p = .009). The most frequent adverse events were cytopenias. CONCLUSIONS: Tocilizumab in pediatric patients with refractory AMR was well tolerated and appeared to stabilize renal function. The utility of tocilizumab in the treatment of AMR in this population should be further explored.

Past and Present Policy Efforts in Achieving Racial Equity in Kidney Transplantation.

Purpose of Review: Inequities in transplant access for underrepresented minorities and people of low socioeconomic status persist. The central principle to organ allocation, the "Final Rule" is grounded on "equitable allocation of cadaveric organs," regardless of background, including race/ethnicity, gender, and socioeconomic status, and there have been ongoing previous and current efforts in achieving the goal of equity in access to transplantation. Recent Findings: Some of these disparities are caused by impeded access to the transplant waiting list (i.e., lack of referral to transplantation, socioeconomic constraints) and are somewhat beyond the purview of Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) policy. This paper examines past and present OPTN/UNOS policy efforts that strive to make access to kidney transplantation more racially equitable. Summary: Past and current policy efforts have brought the transplant community closer to the goal of achieving equity in access to transplantation. More comprehensive data collection may aid in further understanding existing challenges.

Nonalcoholic fatty liver disease prevalence and severity in Asian Americans from the national health and nutrition examination surveys 2017-2018.

Studies have examined nonalcoholic fatty liver disease (NAFLD) prevalence and severity in Asians; however, this is not well understood in Asian Americans (both East and South Asian Americans) as few studies have analyzed this population. We aimed to describe characteristics, prevalence of NAFLD, and its severity in Asian Americans in the National Health and Nutrition Examination Surveys (NHANES) from 2017 to 2018. Respondents 18 years and older with interview, laboratory testing, and transient elastography data were included. Other causes of liver disease were excluded. Controlled attenuation parameter (CAP) cutoff ≥ 274 dB/m, as published in the literature, defined NAFLD. Sensitivity analysis for CAP cutoffs ≥ 248 and ≥302 dB/m were performed. We found that 450 out of 3639 respondents were Asian Americans, and prevalence using CAP ≥ 274 dB/m was 43.23%. Using sensitivity analysis cutoffs of CAP ≥ 248 dB/m and CAP ≥ 302 dB/m, the prevalence was 57.38% and 28.03%, respectively. Compared with non-Asian Americans with NAFLD, Asian Americans with NAFLD had significantly lower body mass index (BMI) and less prevalent smoking history. Comorbidities, such as prediabetes, diabetes, and hypertension, were not significantly different between Asian and non-Asian Americans with NAFLD. Compared to non-Asian Americans with NAFLD, Asian Americans with NAFLD exhibited higher aminotransferases and triglycerides. Fibrosis assessed by transient elastography was not significantly different between Asian and non-Asian Americans with NAFLD. Despite decreased prevalence of BMI ≥ 30 kg/m2 , Asian Americans experienced similar NAFLD prevalence with increased hepatocellular injury and triglyceridemia compared to non-Asian Americans. Fibrosis stages were similar to non-Asian Americans.

Use of a donor-derived cell-free DNA assay to monitor treatment response in pediatric renal transplant recipients with allograft rejection.

BACKGROUND: Detection of donor-derived cell-free DNA (dd-cfDNA) reliably identifies allograft rejection in pediatric and adult kidney transplant (KT) recipients. Here, we evaluate the utility of dd-cfDNA for monitoring response to treatment among pediatric renal transplant recipients suffering graft rejection. METHODS: 58 pediatric transplant recipients were enrolled between April 2018 and March 2020 and underwent initial dd-cfDNA testing to monitor for rejection. Allograft biopsy was performed for dd-cfDNA scores >1.0%. Patients with histologically proven rejection formed the study cohort and underwent appropriate treatment. Results of dd-cfDNA, serum creatinine (SCr), biopsy findings, and treatment outcomes were evaluated. Standard statistical analyses were applied. RESULTS: Nineteen of 58 (31%) patients had dd-cfDNA score >1.0%, of which 18 (94.7%) had biopsy-proven rejection. Median dd-cfDNA value was 1.90% (interquartile range 1.43%-3.23%), and biopsy results showed 11 patients (61.1%) with antibody-mediated rejection (AMR), 2 patients (11.1%) with T-cell mediated rejection (TCMR), and 5 patients (27.7%) with mixed AMR/TCMR. SCr at time of biopsy was 1.28 ± 1.09 mg/dl. Following treatment, dd-cfDNA scores decreased for all types of rejection but still remained >1.0% in both AMR (1.50% [0.90%-3.10%]) and mixed (1.40% [0.95%-4.15%]) groups. Repeat dd-cfDNA values were <1.0% for patients with TCMR (0.20%-0.28%). SCr showed minimal change from pre-treatment levels regardless of rejection subtype. CONCLUSIONS: Patients with TCMR may be reliably followed by dd-cfDNA; however, it remains unclear whether persistently elevated dd-cfDNA levels in AMR is a reflection of ongoing subclinical rejection or an inherent limitation of the assay's utility.

A Clinical Tool to Guide Selection and Utilization of Marginal Donor Livers With Graft Steatosis in Liver Transplantation.

BACKGROUND: Donor liver biopsy (DLBx) in liver transplantation provides information on allograft quality; however, predicting outcomes from these allografts remains difficult. METHODS: Between 2006 and 2015, 16 691 transplants with DLBx were identified from the Standard Transplant Analysis and Research database. Cox proportional hazard regression analyses identified donor and recipient characteristics associated with 30-d, 90-d, 1-y, and 3-y graft survival. A composite model, the Liver Transplant After Biopsy (LTAB) score, was created. The Mini-LTAB was then derived consisting of only donor age, macrosteatosis on DLBx, recipient model for end-stage liver disease score, and cold ischemic time. Risk groups were identified for each score and graft survival was evaluated. P values <0.05 were considered significant. RESULTS: The LTAB model used 14 variables and 5 risk groups and identified low-, mild-, moderate-, high-, and severe-risk groups. Compared with moderate-risk recipients, severe-risk recipients had increased risk of graft loss at 30 d (hazard ratio, 3.270; 95% confidence interval, 2.568-4.120) and at 1 y (2.258; 1.928-2.544). The Mini-LTAB model identified low-, moderate-, and high-risk groups. Graft survival in Mini-LTAB high-risk transplants was significantly lower than moderate- or low-risk transplants at all time points. CONCLUSIONS: The LTAB and Mini-LTAB scores represent guiding principles and provide clinically useful tools for the successful selection and utilization of marginal allografts in liver transplantation.

Comparison of Surgical Resection and Systemic Treatment for Hepatocellular Carcinoma with Vascular Invasion: National Cancer Database Analysis.

INTRODUCTION: Small studies from outside of the USA suggest excellent outcomes after surgical resection for hepatocellular carcinoma (HCC) with vascular invasion. The study aims to (1) compare overall survival after surgical resection and systemic therapy among patients with HCC and vascular invasion and (2) determine factors associated with receipt of surgical resection in a US population. METHODS: HCC patients with AJCC clinical TNM stage 7th T3BN0M0 diagnosed between 2010 and 2017 from the National Cancer Database were analyzed. Cox and logistic regression analyses identified factors associated with overall survival and receipt of surgical resection. RESULTS: Of 11,259 patients with T3BN0M0 HCC, 325 (2.9%) and 4,268 (37.9%) received surgical resection and systemic therapy, respectively. In multivariable analysis, surgical resection was associated with improved survival compared to systemic therapy (adjusted hazard ratio: 0.496, 95% confidence interval: 0.426-0.578) with a median survival of 21.4 and 8.1 months, respectively. Superiority of surgical resection was observed in noncirrhotic and cirrhotic subgroups and propensity score matching and inverse probability of treatment weighting adjusted analysis. Asians were more likely to receive surgical resection, whereas Charlson comorbidity ≥3, elevated alpha-fetoprotein, smaller tumor size, care in a community cancer program, and the South or West region were associated with a lower likelihood of surgical resection. CONCLUSION: HCC patients with vascular invasion may benefit from surgical resection compared to systemic therapies. Demographic and clinical features of HCC patients and region and type of treating facility were associated with surgical resection versus systemic treatment.

Editorial: Disparities in transplantation access and outcomes: mind the gap!

Organ transplantation still remains a problem of supply and demand and presents multiple ethical challenges to our society. Despite numerous targeted interventions and policy reforms, women, underrepresented minorities and patients with low socioeconomic status (SES) continue to have unequal access to transplant. The purpose of this special edition is to highlight disparities in access to transplantation and posttransplant outcomes. Acknowledging that these disparities exist is the first step toward interventions aimed at mitigating this long-standing inequity. This issue provides 10 articles that give the background and summarize relevant literature describing these disparities and identify potential areas of intervention. Most of the data relates to the United States but may reflect patterns encounter in most societies. Each manuscript was written by leaders of international teams in the field of patient advocacy, public health or outcome research in transplantation.

Use of Rituximab for persistent EBV DNAemia, and Its effect on donor-specific antibody development in pediatric renal transplant recipients: A case series.

INTRODUCTION: Persistent EBV DNAemia (PEBV) is associated with late-onset PTLD. The efficacy of rituximab in PEBV is not conclusive. We monitored PEBV and DSA in pediatric kidney transplant patients with or without rituximab. METHODS: 13 PEBV patients received standard treatment with immunosuppression reduction and valganciclovir, with or without IVIG; 5/13 were further treated with rituximab. RESULTS: All Rituximab-treated and 6/7 No-Rituximab patients were EBV seronegative at transplant and seroconverted post-transplant. Peak EBV PCR levels were lower in No-Rituximab than Rituximab patients and all No-Rituximab patients cleared PEBV after standard treatment. Additional 1-2 doses of rituximab reduced EBV PCR levels in all 5 Rituximab patients, 3 cleared PEBV. One No-Rituximab patient developed localized PLTD. None of Rituximab patients developed de novo DSA, while 4/8 No-Rituximab patients did: 2/4 had ABMR. 1/5 Rituximab and 5/8 No-Rituximab patients had acute rejection. There was no change in eGFR between pre-EBV DNAemia and follow-up in Rituximab patients, while reduction in No-Rituximab patients was found. There was no difference in graft and patient survival. CONCLUSIONS: While early intervention with rituximab in pediatric patients with PEBV may reduce viral load and PTLD, we observed a slower development of de novo DSA, and rejection and maintenance of eGFR.

Factors Associated With Detection and Survival of T1 Hepatocellular Carcinoma in the United States: National Cancer Database Analysis.

BACKGROUND: It remains unknown to what extent hepatocellular carcinomas (HCCs) are detected very early (T1 stage; ie, unifocal <2 cm) in the United States. The aim of this study was to investigate the trends and factors associated with very early detection of HCC and resultant outcomes. METHODS: Patients with HCC diagnosed from 2004 through 2014 were identified from the National Cancer Database. Logistic regression was used to identify factors associated with T1 HCC detection, and Cox proportional hazard analyses identified factors associated with overall survival among patients with T1 HCC. RESULTS: Of 110,182 eligible patients, the proportion with T1 HCC increased from 2.6% in 2004 to 6.8% in 2014 (P<.01). The strongest correlate of T1 HCC detection was receipt of care at an academic institution (odds ratio, 3.51; 95% CI, 2.31-5.34). Older age, lack of insurance, high Model for End-Stage Liver Disease (MELD) score, high alpha-fetoprotein, increased Charlson-Deyo comorbidity score, and nonsurgical treatment were associated with increased mortality, and care at an academic center (hazard ratio [HR], 0.27; 95% CI, 0.15-0.48) was associated with reduced mortality in patients with T1 HCC. Liver transplantation (HR, 0.27; 95% CI, 0.20-0.37) and surgical resection (HR, 0.67; 95% CI, 0.48-0.93) were independently associated with improved survival compared with ablation. This is the first study to examine the trend of T1 HCC using the National Cancer Database, which covers approximately 70% of all cancer diagnoses in the United States, using robust statistical analyses. Limitations of the study include a retrospective study design using administrative data and some pertinent data that were not available. CONCLUSIONS: Despite increases over time, <10% of HCCs are detected at T1 stage. The strongest correlates of survival among patients with T1 HCC are receiving care at an academic institution and surgical treatment.