Sex-based Disparities in Access to Liver Transplantation for Waitlisted Patients With Model for End-stage Liver Disease Score of 40.

OBJECTIVE: To determine the association of sex with access to liver transplantation among candidates with the highest possible model for end-stage liver disease score (MELD 40). BACKGROUND: Women with end-stage liver disease are less likely than men to receive liver transplantation due in part to MELD's underestimation of renal dysfunction in women. The extent of the sex-based disparity among patients with high disease severity and equally high MELD scores is unclear. METHODS: Using national transplant registry data, we compared liver offer acceptance (offers received at match MELD 40) and waitlist outcomes (transplant vs death/delisting) by sex for 7654 waitlisted liver transplant candidates from 2009 to 2019 who reached MELD 40. Multivariable logistic and competing-risks regression was used to estimate the association of sex with the outcome and adjust for the candidate and donor factors. RESULTS: Women (N = 3019, 39.4%) spent equal time active at MELD 40 (median: 5 vs 5 days, P = 0.28) but had lower offer acceptance (9.2% vs 11.0%, P < 0.01) compared with men (N = 4635, 60.6%). Adjusting for candidate/donor factors, offers to women were less likely accepted (odds ratio = 0.87, P < 0.01). Adjusting for candidate factors, once they reached MELD 40, women were less likely to be transplanted (subdistribution hazard ratio = 0.90, P < 0.01) and more likely to die or be delisted (subdistribution hazard ratio = 1.14, P = 0.02). CONCLUSIONS: Even among candidates with high disease severity and equally high MELD scores, women have reduced access to liver transplantation and worse outcomes compared with men. Policies addressing this disparity should consider factors beyond MELD score adjustments alone.

Financial burden following adult liver transplantation is common and associated with adverse recipient outcomes.

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p =0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85-8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61-16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p =0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p <0.001). In this multicenter cohort study, nearly 1 in 4 adult recipients of liver transplant experienced a high financial burden, which was significantly associated with delayed or foregone medical care and lower self-reported HRQOL. These findings underscore the need to evaluate and address the financial burden in this population before and after transplantation.

Racial-ethnic differences in liver transplant waitlist outcomes in patients with hepatocellular carcinoma before and after recent changes to allocation policy.

BACKGROUND: In May 2019, liver transplant (LT) allocation policy changed to limit MELD exception points for hepatocellular carcinoma (HCC) to median MELD at transplant minus three (MMaT-3). We evaluated this policy's impact on waitlist outcomes for HCC candidates, by race and ethnicity, hypothesizing that the introduction of the MMaT-3 reduced inequities in waitlist outcomes. METHODS: Retrospective cohort study of the Scientific Registry for Transplant Recipients, including all adult LT candidates (N = 10 751) who received HCC exception points from May 17, 2017 to May 18, 2019 (pre-policy; N = 6627) to May 19, 2019 to March 1, 2021 (post-policy; N = 4124). We compared incidence of LT and waitlist removal for death or becoming too sick pre- and post-policy for non-Hispanic White, non-Hispanic Black, Hispanic/Latinx, and Asian patients using competing risk regression adjusted for candidate characteristics. RESULTS: One-year cumulative incidence of LT decreased significantly pre-/post-policy among White (77.4% vs. 64.5%; p < .01) and Black (76.2% vs. 63.1%; p < .01) candidates only, while a 1-year incidence of death/non-LT waitlist removal decreased significantly only among Hispanics (13.4% vs. 7.5%; p < .01). After covariate adjustment, the effect of the policy change was a significantly decreased incidence of LT for White (SHR: .63 compared to pre-policy; p < .001), Black (SHR: .62; p < .001), and Asian (SHR: .68; p = .002), but no change for Hispanic patients. Only Hispanic patients had a significant decrease in death/waitlist removal after the policy change (SHR:  .69; p = .04). Compared to White patients in the pre-policy era, Hispanic (SHR:  .88, p < .007) and Asian candidates (SHR:  .72; p < .001) had lower unadjusted incidence of LT. This disparity was mitigated in the post-policy era where Hispanic patients had higher likelihood of LT than Whites (SHR: 1.22; p = .002). For the outcome of death/non-LT waitlist removal, the only significant difference was a 42% lower incidence of waitlist removal for Asian compared to White patients in the post-policy era (SHR:  .58; p = .03). CONCLUSION: Among LT recipients with HCC, racial/ethnic subpopulations were differentially affected by the MMAT-3 policy, resulting in a post-policy reduction of some of the previous disparities.

Single-center experience with early liver transplantation for acute alcohol-related hepatitis-Limitations of the SALT score and directions for future study.

Alcohol-related liver disease (ALD) is the leading indication for liver transplantation worldwide. Since Mathurin et al. described their experience in providing early liver transplantation for patients with ALD in 2011, other centers have followed suit with generally favorable survival outcomes. This patient population poses a unique clinical challenge given the expedited nature of the evaluation and the lack of any significant sobriety period prior to transplantation. The SALT (Sustained Alcohol Use Post-Liver Transplant) score is a standardized psychometric tool increasingly used to help stratify the risk of relapse and guide listing decisions for these challenging clinical situations. In 2018, our center introduced a protocol for early liver transplantation for acute alcohol-related hepatitis (AAH). In this article, we offer a retrospective review of 26 patients transplanted between May 2018 and May 2021, including at least 1-year follow-up, and compare outcomes to initial SALT scores; we further identify additional factors that may impact post-transplant success. As transplant committees continue to weigh the ethical dilemma of denying lifesaving treatment against the obligation to remain stewards of a limited resource, we aim to contribute to a more nuanced understanding of risk regarding early transplantation for ALD.

Impact of Portable Normothermic Machine Perfusion for Liver Transplantation From Adult Deceased Donors.

OBJECTIVE: To assess how liver allografts preserved using portable normothermic machine perfusion (NMP) compare against those that underwent ischemic cold storage (ICS) in the setting of donation after brain death (DBD) and donation after circulatory death (DCD) liver transplantation (LT). BACKGROUND: Compared with conventional ICS, NMP may offer more homeostatic preservation, permit physiological assessment of organ function, and provide opportunities for graft improvement/modification. We report a single-center US experience of liver NMP. METHODS: A single-center, retrospective analysis of collected data on 541 adult whole LTs from 469 DBD donors [NMP (n = 58) vs ICS (n = 411)] and 72 DCD donors [NMP (n = 52) vs ICS (n = 20)] between January 2016 and December 2022. RESULTS: In DBD LT, male sex [odds ratio (95% CI): 1.83 (1.08-3.09)] and >10% macrosteatosis of the donor liver [1.85 (1.10-3.10)] were statistically significant independent risk factors of early allograft dysfunction (EAD). Donor age >40 years and cold ischemia time >7 hours were independent risk factors of reperfusion syndrome (RPS). One-year, 3-year, and 5-year incidences of ischemic cholangiopathy (IC) did not differ significantly in DBD cases between the NMP and ICS cohorts. In DCD LT, NMP was an independent protective factor against EAD [0.11 (0.03-0.46)] and RPS [0.04 (0.01-0.25)]. The incidence of IC in the DCD cases at 1-year and 3-year time points was significantly lower in the NMP cohort (1.9% compared with 20% in the ICS group). CONCLUSIONS: Compared with conventional ICS, NMP can significantly reduce the incidence of EAD, RPS, and IC after DCD LT.

Resection of NAFLD/NASH-related Hepatocellular Carcinoma (HCC): Clinical Features and Outcomes Compared with HCC Due to Other Etiologies.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the leading causes of hepatocellular carcinoma (HCC) worldwide. Limited data exist on surgical outcomes for NAFLD/NASH-related HCC compared with other HCC etiologies. We evaluated differences in clinicopathological characteristics and outcomes of patients undergoing surgical resection for NAFLD/NASH-associated HCC compared with other HCC etiologies. METHODS: Demographic, clinicopathological features, and survival outcomes of patients with surgically resected HCC were collected. NAFLD activity score (NAS) and fibrosis score were assessed by focused pathologic review in a subset of patients. RESULTS: Among 492 patients screened, 260 met eligibility (NAFLD/NASH [n = 110], and other etiologies [n = 150]). Median age at diagnosis was higher in the NAFLD/NASH HCC cohort compared with the other etiologies cohort (66.7 vs. 63.4 years, respectively, P = .005), with an increased percentage of female patients (36% vs. 18%, P = .001). NAFLD/NASH-related tumors were more commonly >5 cm (66.0% vs. 45%, P = .001). There were no significant differences in rates of lymphovascular or perineural invasion, histologic grade, or serum AFP levels. The NAFLD/NASH cohort had lower rates of background liver fibrosis, lower AST and ALT levels, and higher platelet counts (P < .01 for all). Median overall survival (OS) was numerically shorter in NAFLD/NASH vs other etiology groups, however, not statistically significant. CONCLUSIONS: Patients with NAFLD/NASH-related HCC more commonly lacked liver fibrosis and presented with larger HCCs compared with patients with HCC from other etiologies. No differences were seen in rates of other high-risk features or survival. With the caveat of sample size and retrospective analysis, this supports a similar decision-making approach regarding surgical resection for NAFLD/NASH and other etiology-related HCCs.

Donor-derived disorders of hemostasis and thrombosis in liver transplantation: Considerations for deceased donor liver selection.

OLT is known to be associated with a precarious perioperative hemostatic state due to dysregulation of procoagulant and anticoagulant factors, endothelial injury, and inflammation. Transmission of inherited bleeding and clotting disorders from the liver donor to the recipient may further complicate hemostasis during and after transplantation. As a result, consideration of congenital coagulation disorders in the liver donor is a practical concern for donor selection. However, there is no clear consensus regarding the selection of donors with known or suspected thrombophilia or bleeding disorders. While multiple case reports and retrospective studies, subject to reporting bias, describe donor-derived thrombophilic and bleeding disorders, there are no large-scale studies in the adult liver transplant literature that examine the frequency of transmission, utility of donor screening, or clinical impact of donor hemostatic disorders. Based on the reported literature, we summarize our approach for donor selection with an aim to balance improved organ utility and optimal post-transplant outcomes.

Continuous versus Pulsatile Flow in 24-Hour Vascularized Composite Allograft Machine Perfusion in Swine: A Pilot Study.

INTRODUCTION: Multiple perfusion systems have been investigated on vascularized composite allografts, with various temperatures and different preservation solutions, most using continuous flow (CF). However, physiological flow is pulsatile and provides better outcomes in kidney and lung ex vivo perfusions. The objective of this pilot study is to compare pulsatile flow (PF) with CF in our 24-h subnormothermic machine perfusion protocol for swine hindlimbs. METHODS: Partial hindlimbs were harvested from Yorkshire pigs and perfused with a modified Steen solution at 21°C for 24 h either with CF (n = 3) or with pulsatile flow (PF) at 60 beats/min (n = 3). Perfusion parameters, endothelial markers, and muscle biopsies were assessed at different timepoints. RESULTS: Overall, lactate levels were significantly lower in the PF group (P = 0.001). Glucose uptake and potassium concentration were similar in both groups throughout perfusion. Total nitric oxide levels were significantly higher in the PF group throughout perfusion (P = 0.032). Nitric oxide/endothelin-1 ratio also tends to be higher in the PF group, reflecting a potentially better vasoconductivity with PF, although not reaching statistical significance (P = 0.095). Arterial resistances were higher in the PF group (P < 0.001). Histological assessment did not show significant difference in muscular injury between the two groups. Weight increased quicker in the CF group but reached similar values with the PF after 24 h. CONCLUSIONS: This pilot study suggests that PF may provide superior preservation of vascularized composite allografts when perfused for 24 h at subnormothermic temperatures, with potential improvement in endothelial function and decreased ischemic injury.

Impact of donor sex on hepatocellular carcinoma recurrence in liver transplantation after brain death.

BACKGROUND: Hepatocellular carcinoma (HCC) is predominantly seen in males but has a better prognosis in females. No prior studies have investigated HCC recurrence based on sex combination following liver transplant donated after brain death (DBDLT). This study sought to elucidate the effects of donor and recipient sex on HCC recurrence rates. METHODS: 9232 adult recipients from the United Network for Organ Sharing (UNOS) database who underwent DBDLT for HCC from 2012 to 2018 were included. Donor-recipient pairs were divided into (1) female donor/female recipient (F-F) (n = 1089); (2) male donor/female recipient (M-F) (n = 975); (3) female donor/male recipient (F-M) (n = 2691); (4) male donor/male recipient (M-M) (n = 4477). The primary prognostic outcome was HCC recurrence. A multivariable competing risk regression analysis was used to assess prognostic influences. RESULTS: The median recipient age and model for end-stage liver disease (MELD) scores were similar among the four groups. Livers of male recipients demonstrated greater in size and number of HCC (both p-values were <.0001). There was also a higher rate of vascular invasion in male recipients compared to female (p < .0001). Competing risk analyses showed that the cumulative HCC recurrence rate was significantly lower in the M-F group (p = .013). After adjusting for tumor characteristics, liver grafts from male donors were associated with a lower HCC recurrence rate in female recipients (HR: .62 95%CI: .42-.93) (p = .021). CONCLUSION: In DBDLT, male donor to female recipient pairing exhibited lower HCC recurrence rates. SUMMARY: Lowest rates of HCC recurrence were confirmed among the female recipients of male donor grafts group in the deceased donor LT cohort. A competing risk multivariable regression analysis demonstrated that male donor sex was significantly associated with low HCC recurrence in female but not male recipients.

The Effect of Language on Access to Timely COVID-19 Vaccination of Solid Abdominal Organ Transplant Recipients.

In dynamic healthcare environments including the COVID-19 pandemic, it is paramount to communicate health recommendations expediently and clearly. Research has shown social determinants of health affect the impact of COVID-19 on abdominal transplant recipients, but there has been less research on the effect of language proficiency. This is a cohort study of time to first COVID-19 vaccination among abdominal organ transplant recipients in an academic medical center in Boston, MA between 18 December 2020, and 15 February 2021. Cox proportional hazards analysis of time to vaccination by preferred language were adjusted for race, age group, insurance, and transplanted organ. Among 3001 patients, 53% were vaccinated during the study period. Language preference other than English was independently associated with delay to vaccination (0.64, p = 0.001), on adjusted analysis. In addition, Black, Hispanic and other race patients were less likely to be vaccinated than white patients (0.58, 0.67, 0.68 vs. reference, all p < 0.03). Language preference other than English is an independent barrier to solid abdominal organ transplant recipients' access to timely COVID-19 vaccination. Equity in care should be improved by providing targeted services to minority language speakers.

Activation of autophagy during normothermic machine perfusion of discarded livers is associated with improved hepatocellular function.

Liver transplantation is hampered by a severe shortage of donor organs. Normothermic machine perfusion (NMP) of donor livers allows dynamic preservation in addition to viability assessment before transplantation. Little is known about the injury and repair mechanisms induced during NMP. To investigate these mechanisms, we examined gene and protein expression changes in a cohort of discarded human livers, stratified by hepatocellular function, during NMP. Six human livers acquired through donation after circulatory death (DCD) underwent 12 h of NMP. Of the six livers, three met predefined criteria for adequate hepatocellular function. We applied transcriptomic profiling and protein analysis to evaluate temporal changes in gene expression during NMP between functional and nonfunctional livers. Principal component analysis segregated the two groups and distinguished the various perfusion time points. Transcriptomic analysis of biopsies from functional livers indicated robust activation of innate immunity after 3 h of NMP followed by enrichment of prorepair and prosurvival mechanisms. Nonfunctional livers demonstrated delayed and persistent enrichment of markers of innate immunity. Functional livers demonstrated effective induction of autophagy, a cellular repair and homeostasis pathway, in contrast to nonfunctional livers. In conclusion, NMP of discarded DCD human livers results in innate immune-mediated injury, while also activating autophagy, a presumed mechanism for support of cellular repair. More pronounced activation of autophagy was seen in livers that demonstrated adequate hepatocellular function.NEW & NOTEWORTHY We demonstrate that ischemia-reperfusion injury occurs in all livers during NMP, though there are notable differences in gene expression between functional and nonfunctional livers. We further demonstrate that activation of the liver's repair and homeostasis mechanisms through autophagy plays a vital role in the graft's response to injury and may impact liver function. These findings indicate that liver autophagy might be a key therapeutic target for rehabilitating the function of severely injured or untransplantable livers.

Increasing Frequency of Interpreting Services is Associated With Shorter Peri-operative Length of Stay.

BACKGROUND: Patients with limited English proficiency have barriers to accessing care. Rather than a binary use or no use, this study uses granular data on frequency of interpreting services to determine if this frequency is associated with differences in peri-operative length of stay for patients with limited English proficiency. MATERIALS AND METHODS: This is a cross sectional study on length of stay for peri-operative admissions of at least one night during 2018, for patients who used medical interpreting services in an academic medical center in Boston, Massachusetts. The participants are split into quartiles of ascending number of interpreting events per day. The exposure for the primary outcome is the frequency of interpreting events per day during peri-operative admission. The primary study outcome measurement is peri-operative length of stay in days. RESULTS: There was a statistically significant decrease in length of stay for patients in the highest two quartiles of interpreting service frequency, compared to the lowest quartile: quartile 2 trended shorter by 1.4 d (95% CI -4.5 to 1.7, P = 0.37), quartile 3 was 4.2 d shorter (95% CI -7.6 to -0.7, P = 0.02), and quartile 4 was 4.6 d shorter (95% CI -8.1 to -1.1, P = 0.01). CONCLUSIONS: More frequent interpreting services per day during peri-operative admission are associated with shorter length of stay in adjusted analysis. The findings merit further study in an intervention to increase use of interpreting services for surgical patients with limited English proficiency to study the impact of increased frequency of culturally competent care.

Stent Diameter, Not Cephalic Arch Anatomy, Predicts Stent Graft Patency in Cephalic Arch Stenosis.

PURPOSE: To investigate the relationship between anatomic factors and primary patency of brachiocephalic arteriovenous fistulae (AVFs) after stent graft (SG) placement for cephalic arch stenosis (CAS). MATERIALS AND METHODS: This retrospective study reviewed all cephalic arch SGs placed in brachiocephalic AVFs in a tertiary academic medical center between 2014 and 2017. Sixty-three patients were included in the study. The mean patient age at the time of SG placement was 62.6 years ± 19, and the mean patient follow-up was 1,994 days ± 353. A cohort of patients (n = 31) who underwent brachiocephalic fistulograms for CAS but only received percutaneous transluminal angioplasty (PTA) was the control group. Patient demographic characteristics, AVF anatomy, SG type, and clinical outcomes were reviewed. The duration of primary cephalic arch patency after SG placement was compared with that after previous PTA. RESULTS: The median AVF age at the time of data retrieval was 345 days. The primary patency of CAS after SG placement at 6 months, 12 months, and 3 years was 64%, 49.9%, and 23.5%, respectively. Primary cephalic arch patency was significantly associated with the SG diameter (P = .007) but not with cephalic vein-axillary vein junction anatomy, size of feeding artery, or SG length (P > .05). The primary patency of CAS in patients treated with PTA only (n = 31) at 6 months, 12 months, and 3 years was 61%, 35%, and 0%, respectively, which was significantly lower than that in patients treated with SG placement (P = .01). CONCLUSIONS: This study showed that the primary patency of CAS after SG placement was significantly higher than that of PTA-only treatment. Moreover, primary cephalic arch patency after SG placement was significantly associated with the SG diameter.

Acceptability and utility of a virtual pediatric transplant peer mentoring program: A mixed-methods analysis of a novel quality improvement program.

BACKGROUND: Adolescent transplant patients are at increased risk for graft loss at a period when they also suffer from illness-related social isolation, which has been exacerbated by the COVID-19 pandemic. The Peer Mentoring Program (PMP), developed in 2018, was adapted to a virtual format in 2020 due to COVID-19. Our objective is to evaluate the acceptability, utility, and potential impact of the in-person and virtual versions of the PMP on participants. METHODS: We performed convergent mixed-methods analysis of the experiences of patients participating in the PMP for quality improvement purposes. RESULTS: Surveys and focus group invitations were sent to 18 current program participants, with 17 patients responding to the survey and 13 patients participating in focus groups. In this study, 82% were satisfied and 88% would recommend PMP; 76% identified other PMP members as people they would like to keep in touch with. Qualitative analysis revealed three themes: (1) a supportive community of peers, (2) reduced isolation, and (3) receiving accurate information from providers. CONCLUSIONS: There is a prominent need for greater peer support among adolescent transplant patients transitioning to adulthood, especially with the increased isolation associated with COVID-19. The virtual adaptation could be an important, permanent supplement to in-person events.

The impact of race and comorbid conditions on adult liver transplant outcomes in obese recipients.

Many prior studies comparing liver transplant outcomes between obese and nonobese recipients found no significant differences in survival. However, obesity is intrinsically associated with demographic factors such as race and comorbidities. Thus, this work aimed to analyze the effects of obesity, in conjunction with these factors, on liver transplant outcomes. OPTN data was analyzed to identify adult-only, first-time liver transplants between 1995 and 2019. Obesity was defined by the CDC obesity classification. Race, insurance status, age, and comorbidities were analyzed together with patient survival and graft survival using a multivariable Cox Proportional-Hazards model and long-term survival with Kaplan-Meier curves. The multivariable models found that being black, older than 50 years, having diabetes, or having nonprivate insurance were all risk factors for both patient survival and graft survival after liver transplant. Adjusting for obesity class, black recipients had a 20% lower patient survival and 23% lower graft survival compared with nonblack recipients. Survival curves verified that obese black liver transplant recipients had poorer long-term patient survival and graft survival compared with both obese nonblack and nonobese recipients. In conclusion, obesity compounds known factors associated with poor outcomes after liver transplantation. Further work is critical to understand why these discrepancies persist.

Temporal trends and impact of willingness to accept organs from donors with hepatitis C virus.

Direct-acting antivirals (DAA) transformed hepatitis C virus (HCV) treatment in 2014; however, their impact on transplant candidates' willingness to accept (CWTA) organs from HCV+ donors remains uncertain. We retrospectively studied Organ Procurement and Transplantation Network data from 2008 to 2019, investigating CWTA different organs from HCV+ donors over time, using segmented multivariable logistic regression, and how that influenced wait-time and deceased-donor transplantation (DDTx) probability, using multivariable logistic or linear regression. We found that DAA availability was associated with a marked increase in CWTA in all organs from HCV+ donors except intestine. By December 2020, 40% of kidney, 33% of kidney-pancreas, 42% of pancreas, over 50% of liver, heart, lung, heart-lung, and 9% of intestine candidates waitlisted were CWTA an organ from HCV+ donors. Compared with pre-DAA, yearly CWTA kidney from HCV+ donors increased post-DAA 1.78 1.811.83 -fold, kidney-pancreas 2 .52 2.78 3.07 -fold, pancreas 3.15 3.69 4.43 -fold, liver 1.53 1.541.56 -fold, heart 1 .92 2.02 .08 -fold, and lung 2.00 2.12 .20 -fold. CWTA kidney and liver from HCV+ donors significantly increased DDTx probability post-DAA (1.98 2.042.1 -fold and 1.24 1.291.33 -fold, respectively) and shortened kidney candidates' wait-time78 90101 days (Mean with 95% CI). CWTA organs from HCV+ donors rose significantly with DAA availability, benefitting kidney and liver candidates with increased DDTx rates and shortened kidney candidates' wait time. Further long-term outcomes investigation and standardized organ from HCV+ donors' education could improve both provider and patient acceptance and utilization.

Practitioner availability rather than surgical quality impacts the utilization of liver transplantation for hepatocellular carcinoma.

BACKGROUND: Liver transplantation (LT) provides better outcome than surgical resection (SR) although both are acceptable surgical options for hepatocellular carcinoma (HCC). It is unclear whether non-clinical factors drive treatment decisions. Our goal is to identify factors that may affect treatment decisions. METHODS: Patients aged 18-74 with T2 HCC undergoing either LT or SR in Surveillance, Epidemiology, and End Results Database from 2004 to 2014 were included. Healthcare resources data were analyzed to assess factors that predict utilization of LT versus SR, adjusted for demographic, clinical outcomes, and socioeconomic factors. RESULTS: 51% of patients (Total N = 2616) received LT, with a substantial state-level variation in LT rates (0.0%-66.9%). Higher LT center density [OR = 1.04 per 1% increment, P < 0.01], male gender (OR = 1.38, P = 0.02), and numbers of potential donors (OR = 1.19, P = 0.03) were positively associated with LT utilization. Conversely, higher incidence of chronic liver disease/cirrhosis (OR = 0.41 per one additional case per 100,000 populations, P = 0.001) and minority populations were negatively correlated with LT utilization. Notably, short-term surgical outcomes (in-hospital LT & SR mortality) were not associated with LT utilization. CONCLUSION: Liver transplant center density and organ availability, but not surgical outcomes, affect utilization of LT. Future studies should focus on increasing availability of resources.

Regulatory B cells require antigen recognition for effective allograft tolerance induction.

Through multiple mechanisms, regulatory B cells (Breg) have been shown to play an important role in the development of allograft tolerance. However, a careful understanding of the role of antigen-specificity in Breg-mediated allograft tolerance has remained elusive. In experimental models of islet and cardiac transplantation, it has been established that Bregs can be induced in vivo by anti-CD45RB ± anti-TIM1antibody treatment, resulting in prolonged, Breg-dependent allograft tolerance. The importance of Breg antigen recognition has been suggested but not confirmed through adoptive transfer experiments, using tolerant WT C57BL/6 animals challenged with either BALB/c or C3H grafts. However, the importance of receptor-specificity has not been formally tested. Here, we utilize the novel ovalbumin-specific B cell receptor transnuclear (OBI) mice in multiple primary tolerance and adoptive transfer experiments to establish that Breg-dependent allograft tolerance relies on antigen recognition by B cells. Additionally, we identify that this Breg-dependent tolerance relies on the function of transforming growth factor-ß. Together, these experiments mark important progress toward understanding how best to improve Breg-mediated allograft tolerance.

Immediate administration of antiviral therapy after transplantation of hepatitis C-infected livers into uninfected recipients: Implications for therapeutic planning.

The practice of transplanting hepatitis C (HCV)-infected livers into HCV-uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct-acting antivirals (DAAs) provide an opportunity to treat donor-derived HCV-infection and should be administered early in the posttransplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV-positive donor organs. We report the results of a trial in which 14 HCV-negative patients underwent successful liver transplantation from HCV-positive donors. Nine patients received viremic (nucleic acid testing [NAT]-positive) livers and started a 12-week course of oral glecaprevir-pibrentasvir within 5 days of transplant. Five patients received livers from HCV antibody-positive nonviremic donors and were followed using a reactive approach. Survival in NAT-positive recipients is 100% at a median follow-up of 46 weeks. An immediate treatment approach for HCV NAT-positive liver transplantation into uninfected recipients is safe and efficacious. Securing payer approval for DAAs early in the posttransplant course could enable need-based allocation of HCV-positive donor organs irrespective of candidate HCV status, while averting chronic HCV allograft infection.

Is It Time to Reconsider the Milan Criteria for Selecting Patients With Hepatocellular Carcinoma for Deceased-Donor Liver Transplantation?

Liver transplantation (LT) is considered the optimal treatment for hepatocellular carcinoma (HCC) because it removes tumor as well as the underlying cirrhotic liver. Because of a global organ shortage, LT for patients with HCC is limited to patients with expected survival comparable to that of nonmalignant indications. Therefore, identifying patients with lower rates of HCC recurrence and higher rates of survival is critical. International guidelines have considered the Milan Criteria (MC) the standard for selecting patients with HCC for deceased-donor LT (DDLT). However, several alternative criteria have been reported in the Western world. Interestingly, the two most recent models combining α-fetoprotein level, number of nodules, and size of the largest nodule have been shown to outperform MC in identifying patients with low risk of HCC recurrence or those who will survive for 5 years after liver transplantation. In addition, new models overcome limitations of MC in improving classification of high- versus low-risk patients with HCC for DDLT. These recent scoring systems also provide clinicians with user-friendly tools to better identify patients at lower risk of recurrence. Conclusion: Although most Western countries still select patients based on MC, there is a mounting change in recent practice patterns regarding the selection of patients with HCC for DDLT. Herein, we describe how alternative criteria should lead to reconsideration of MC as it applies to selecting patients with HCC for DDLT in international guidelines.