Liver transplantation for biliary cysts: perioperative and long-term outcomes.

BACKGROUND: Biliary cysts (BC) is a rare indication for orthotopic liver transplantation (OLT). METHODS: We queried the UNOS dataset to identify patients who underwent OLT for Caroli's disease (CD) and choledochal cysts (CC). All patients with BC (CD + CC) were compared to a cohort of patients transplanted for other indications. Patients with CC were also compared to those with CD. Cox proportional hazard model was performed to assess predictors of graft and patient survival. RESULTS: 261 patients underwent OLT for BC. Patients with BC had better pre-operative liver function compared to those transplanted for other indications. 5-year graft and patient survival were 72% and 81%, respectively, similar to those transplanted for other indications after matching. Patients with CC were younger and had increased preoperative cholestasis compared to those with CD. Donor age, race, and gender were predictors of poor graft and patient survival in patients transplanted for CC. CONCLUSIONS: Patients with BC have similar outcomes to those transplanted for other indications and more frequently require MELD score exception. In patients transplanted for choledochal cysts, female gender, donor age, and African-American race were independent predictors of poor survival. Pediatric patients transplanted for Caroli's disease had better survival compared to adults.

Results of a data-driven performance improvement initiative in organ donation.

New metrics for organ procurement organization (OPO) performance utilize National Center for Health Statistics data to measure cause, age, and location consistent (CALC) deaths. We used this denominator to identify opportunities for improved donor conversion at one OPO, Indiana Donor Network (INOP). We sought to determine whether such analyses are immediately actionable for quality improvement (QI) initiatives directed at increased donor conversion. CALC-based assessment of INOP's performance revealed an opportunity to improve conversion of older donors. Following the QI initiative, INOP donor yield rose by 44%, while organs transplanted rose by 29%. These changes tolerated temporary disruption around the COVID-19 pandemic. Improved donor yield was primarily seen in older groups identified by CALC-based methods. Process changes in resource allocation and monitoring were associated with a 57% increase in the number of potential donors approached in the QI period and a subsequent rise in the number of potential donor referrals, suggesting positive feedback at area hospitals. Post-intervention, INOP's projected donation performance rose from 51st to 18th among all OPOs. OPOs can use CALC death data to accurately assess donor conversion by categories including age and race/ethnicity. These data can be used in real time to inform OPO-level processes to maximize donor recovery.

Perioperative Challenges in Patients Transplanted with Livers from Extreme Obese Donors.

The combination of rising rates of obesity and the shortage of deceased donor livers have forced the consideration of marginal liver donors in terms of body mass index (BMI) for liver transplantation (LT). To date, there are still conflicting data on the impact of donor obesity on post-LT outcomes. We analyzed all patients undergoing LT alone in the United States (US) from October 2005 through December 2019 using the United Network of Organ Sharing (UNOS) data set. We categorized donor BMI >40 kg/m2 as extremely obese (EO). Primary endpoints included 30-day perioperative mortality and early graft loss (EGL) within 7 days. A subgroup analysis was performed for the EO donor group to assess how macrovesicular steatosis (MaS) >30% affects 30-day mortality and EGL within 7 days. A total of 72,616 patients underwent LT during the study period. The 30-day perioperative mortality was significantly higher in the EO donor group (P = 0.02). On multivariate analysis, recipients undergoing LT with EO donors had a 38% higher 30-day mortality risk (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.21-1.69) and 53% increased risk of EGL (OR, 1.53; 95% CI, 1.22-1.90). MaS >30% was independently associated with a 2-fold increased risk of 30-day mortality (P = 0.003) and 3.5-fold increased risk of EGL within 7 days (P < 0.001). The impact of MaS >30% in EGL was 2-fold for all patients transplanted during the study period compared with 3.5-fold in the EO donor group. There is an increased risk of EGL and 30-day perioperative mortality in recipients transplanted with EO donors. Future studies are warranted in morbid and super obese donors to assess the possible effect of obesity-related proinflammatory factors in EGL.

Utilization of deceased donors during a pandemic: argument against using SARS-CoV-2-positive donors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become an unprecedented pandemic that has impacted society, disrupted hospital functions, strained health care resources, and impacted the lives of transplant professionals. Despite this, organ failure and the need for transplant continues throughout the United States. Considering the perpetual scarcity of deceased donor organs, Kates et al present a viewpoint that advocates for the utilization of coronavirus disease 2019 (COVID-19)-positive donors in selected cases. We present a review of the current literature that details the potential negative consequences of COVID-19-positive donors. The factors we consider include (1) the risk of blood transmission of SARS-CoV-2, (2) involvement of donor organs, (3) lack of effective therapies, (4) exposure of health care and recovery teams, (5) disease transmission and propagation, and (6) hospital resource utilization. While we acknowledge that transplant fulfills the mission of saving lives, it is imperative to consider the consequences not only to our recipients but also to the community and to health care workers, particularly in the absence of effective preventative or curative therapies. For these reasons, we believe the evidence and risks show that COVID-19 infection should continue to remain a contraindication for donation, as has been the initial response of donation and transplant societies.

The COVID-19 pandemic: A community approach.

An unprecedented global pandemic caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has quickly overwhelmed the health care systems worldwide. While there is an absence of consensus among the community in how to manage solid organ transplant recipients and donors, a platform provided by the American Society of Transplantation online community "Outstanding Questions in Transplantation," hosted a collaborative multicenter, multinational discussions to share knowledge in a rapidly evolving global situation. Here, we present a summary of the discussion in addition to the latest published literature.

Importance of incorporating standardized, verifiable, objective metrics of organ procurement organization performance into discussions about organ allocation.

Identifying and supporting specific organ procurement organizations (OPOs) with the greatest opportunity to increase donation rates could significantly increase the number of organs available for transplant. Accomplishing this is complicated by current Scientific Registry of Transplant Recipients/Centers for Medicare & Medicaid Services metrics of donation rates and OPO performance that rely on eligible deaths. These data are self-reported and unverifiable and have been shown to underestimate potential organ donors. We examine the limitations of current OPO performance/donation metrics to inform discussions related to strategies to increase donation. We propose changing to a simple, verifiable, and uniformly applied donation metric. This would allow the transplant community to (1) better understand inherent differences in donor availability based on geography and (2) identify underperforming areas that would benefit from systems improvement agreements to increase donation rates.

Patterns of geographic variability in mortality and eligible deaths between organ procurement organizations.

Eligible deaths are currently used as the denominator of the donor conversion ratio to mitigate the effect of varying mortality patterns in the populations served by different organ procurement organizations (OPOs). Eligible death is an OPO-reported metric rather than a product of formal epidemiological analysis, however, and may be confounded with OPO performance. Using Scientific Registry of Transplant Recipients and Centers for Disease Control and Prevention data, patterns of mortality and eligible deaths within each OPO were analyzed with the use of formal geostatistical analysis to determine whether eligible deaths truly reflect the geographic patterns they are intended to mitigate. There was a 2.1-fold difference in mortality between the OPOs with the highest and lowest rates, with significant positive spatial autocorrelation evident in mortality rates (Moran I = .110; P < .001), meaning geographically proximate OPOs tended to have similar mortality rates. The eligible death ratio demonstrated greater variability, with a 4.5-fold difference between the OPOs with the highest and lowest rates. Contrary to the pattern of mortality rates, the geographic distribution of eligible deaths among OPOs was random (Moran I = -.002; P = .410). This finding suggests geographic patterns do not play a significant role in eligible deaths, thus questioning its continuing use in OPO performance comparisons.

Long term outcomes of patients transplanted for hepatocellular carcinoma with human immunodeficiency virus infection.

BACKGROUND: We aimed to study outcomes in HIV + patients with HCC in the US following Liver Transplantation (LT) using the UNOS dataset. METHODS: The database was queried from 2003 to 2016 for patients undergoing LT with HCC, HIV+, and HCC/HIV+. RESULTS: Out of 17,397 LT performed for HCC during the study period, 113 were transplanted for HCC with HIV infection (91 isolated livers). Patients transplanted for HCC/HIV+ were younger (55.54 ± 5.89 vs 58.80 ± 7.37, p < 0.001), had lower total bilirubin (1.20 vs 1.60, p = 0.042) significantly lower BMI (25.35 ± 4.43 vs 28.39 ± 5.17, p < 0.001) and were more likely to be co-infected with HBV (25.3% vs 8.2% p < 0.001) than those transplanted for HCC alone. HCC/HIV + patients were found to have a 3.8 fold increased risk of peri-operative mortality at 90 days after matching. HCC/HIV + recipients had 54% decreased long-term survival within the HCC cohort. Our initial analysis of overall graft and patient survival found significant differences between HCC/HIV and HCC/HIV + recipients. However, these variances were lost after case-matching. Recurrence and disease free survival were similar in HCC alone vs HCC/HIV + recipients. CONCLUSIONS: Our analysis suggests that excellent outcomes can be achieved in selected patients with HCC/HIV+.

Socioeconomic factors as predictors of organ donation.

BACKGROUND: Despite numerous initiatives to increase solid organs for transplant, the gap between donors and recipients widens. There is little in the literature identifying socioeconomic predictors for donation. We evaluate the correlation between socioeconomic factors and familial authorization for donation. METHODS: A retrospective analysis of adult potential donor referrals between 2007 and 2012 to our organ procurement organization (OPO) was performed. Potential donor information was obtained from the OPO database, death certificates, and the US Census Report. Data on demographics, education, residence, income, registry status, cause and manner of death, as well as OPO assessments and approach for donation were collected. End point was familial authorization for donation. RESULTS: A total of 1059 potential donors were included, with an overall authorization rate of 47%. The majority was not on the donor registry (73%). Younger donors (18-39 y: odds ratio [OR] = 4.9, P < 0.001; 40-60 y: OR = 2.1, P < 0.001), higher levels of education (college: OR = 2.5, P = 0.005; graduate studies: OR = 3.9, P = 0.002), prior listing on the donor registry (OR = 10.3, P < 0.001), and residence in counties with lower poverty rates than the US rates (OR = 1.7, P = 0.02) were independently associated with higher authorization rates. Decoupling (OR = 3.1, P < 0.001) and donation first mentioned by the local health care provider (OR = 1.8, P = 0.01) were also independently associated with higher authorization rates. CONCLUSIONS: Donor registration correlated most strongly with the highest authorization rates. These results indicate that public educational efforts in populations with unfavorable socioeconomic considerations may be beneficial in improving donor registration. Collaborations with local providers as well as OPO in-hospital assessments and approach techniques can help with improving authorization rates.

Liver transplantation for fibrolamellar hepatocellular carcinoma: A national perspective.

BACKGROUND: Fibrolamellar Hepatocellular Carcinoma (FL-HCC) is a rare primary liver tumor that usually presents in younger patients without underlying liver disease. METHODS: We queried the United Network of Organ Sharing (UNOS) database between October 1988 and January 2013 to evaluate outcomes in patients with FL-HCC undergoing liver transplantation in the United States compared to patients with conventional Hepatocellular Carcinoma (HCC). RESULTS: Sixty-three patients were identified (57% female, mean age 30 years). Only one patient (2%) had an associated Hepatitis C Virus. Mean Model for End-Stage Liver Disease (MELD) score at the time of transplantation was 11.3. Mean waiting time was 325 days and mean cold ischemic time was 6 hr. Overall survival of FL-HCC patients at 1, 3, and 5 years was 96%, 80%, and 48% as compared to HCC patients whose rates were 89%, 77%, and 68%. Six patients had tumor recurrence (10%). The Cox Model demonstrated that MELD and cold ischemic time are the strongest predictors of overall survival in FL-HCC patients. Age and wait time were not associated with poor patient survival in this series. CONCLUSIONS: Good results can be obtained in selected patients transplanted for FL-HCC. FL-HCC patients had similar survival compared to those transplanted for HCC. J. Surg. Oncol. 2017;115:319-323. © 2016 Wiley Periodicals, Inc.

Decreased graft survival in liver transplant recipients of donors with positive blood cultures: a review of the United Network for Organ Sharing dataset.

Liver transplantation using blood culture positive donors (BCPD) has allowed a significant expansion of the donor pool. We aimed to characterize BCPD and assess the outcomes of BCPD liver transplant recipients. We retrieved data from the United Network for Organ Sharing (UNOS) registry on all adults who underwent primary, single-organ deceased-donor liver transplantation in the USA between 2008 and 2013. Patients were classified into two cohorts: the BCPD cohort and the non-BCPD cohort. One-year graft and patient survival were compared between cohorts using Kaplan-Meier estimates and Cox models. A total of 28 961 patients were included. There were 2316 (8.0%) recipients of BCPD. BCPD were more likely to be older, female, black, diabetic, hypertensive, and obese compared to non-BCPD. Graft survival was significantly lower in BCPD recipients compared to non-BCPD recipients (Kaplan-Meier, 0.85 vs. 0.87; P = 0.009). Results remained significant in propensity-matched analysis (P = 0.038). BCPD was independently associated with decreased graft survival (adjusted HR; 1.10, 95% CI 1.01-1.20; P = 0.04). There were no significant differences in patient survival between study groups. BCPD was associated with decreased graft survival in liver transplant recipients. Studies are needed to identify subgroups of BCPD with the highest risk of graft failure and characterize the underlying pathogenic mechanisms.

Care of the mother-infant dyad: a novel approach to conducting and evaluating neonatal resuscitation simulation training in Bihar, India.

BACKGROUND: As the global under-five mortality rate declines, an increasing percentage is attributable to early neonatal mortality. A quarter of early neonatal deaths are due to perinatal asphyxia. However, neonatal resuscitation (NR) simulation training in low-resource settings, where the majority of neonatal deaths occur, has achieved variable success. In Bihar, India, the poorest region in South Asia, there is tremendous need for a new approach to reducing neonatal morality. METHODS: This analysis aims to assess the impact of a novel in-situ simulation training program, developed by PRONTO International and implemented in collaboration with CARE India, on NR skills of nurses in Bihar. Skills were evaluated by clinical complexity of the simulated scenario, which ranged from level 1, requiring NR without a maternal complication, to level 3, requiring simultaneous management of neonatal and maternal complications. A total of 658 nurses at 80 facilities received training 1 week per month for 8 months. Simulations were video-recorded and coded for pre-defined clinical skills using Studiocode™. RESULTS: A total of 298 NR simulations were analyzed. As simulation complexity increased, the percentage of simulations in which nurses completed key steps of NR did not change, even with only 1-2 providers in the simulation. This suggests that with PRONTO training, nurses were able to maintain key skills despite higher clinical demands. As simulation complexity increased from level 1 to 3, time to completion of key NR steps decreased non-significantly. Median time to infant drying decreased by 7.5 s (p = 0.12), time to placing the infant on the warmer decreased by 21.7 s (p = 0.27), and time to the initiation of positive pressure ventilation decreased by 20.8 s (p = 0.12). Nevertheless, there remains a need for improvement in absolute time elapsed between delivery and completion of key NR tasks. CONCLUSIONS: PRONTO simulation training enabled nurses in Bihar to maintain core NR skills in simulation despite demands for higher-level triage and management. Although further evaluation of the PRONTO methodology is necessary to understand the full scope of its impact, this analysis highlights the importance of conducting and evaluating simulation training in low-resource settings based on simultaneous care of the mother-infant dyad.

Simeprevir and sofosbuvir with or without ribavirin to treat recurrent genotype 1 hepatitis C virus infection after orthotopic liver transplantation.

Although combination simeprevir (SIM) plus sofosbuvir (SOF) is an approved regimen for genotype 1 chronic hepatitis C virus (HCV), data regarding its safety and efficacy in liver transplant recipients remain limited. A multicenter retrospective study was performed to determine the efficacy and tolerability of a 12-week regimen of SIM/SOF with or without ribavirin (RBV) in 56 consecutive liver transplant recipients in 2014; 79% of patients had genotype 1a, 14% had cirrhosis, and 73% were treatment experienced. Sustained virological response at 12 weeks (SVR12) was 88% by intention to treat analysis (95% confidence interval, 84%-90%). Four patients relapsed, but no on-treatment virological failures occurred. The Q80K polymorphism did not impact SVR12, but there was a trend toward decreased sustained virological response with advanced fibrosis (P = 0.18). HCV RNA was detectable at treatment week 4 in 21% of patients, and those who had detectable levels were less likely to achieve SVR12 (58% versus 95%; P = 0.003). Five patients had baseline Child-Pugh class B cirrhosis, and 2 of them died (1 following early discontinuation of therapy). An additional discontinuation resulted from a severe photosensitivity reaction in a patient on concomitant cyclosporine. Seven patients receiving RBV developed progressive anemia requiring intervention. Immunosuppression dose modifications were minimal. SIM/SOF for 12 weeks was effective and well tolerated by compensated liver transplant recipients especially when administered without concomitant RBV or cyclosporine. SIM/SOF appears to have a niche as the only 12-week RBV-free treatment regimen currently recommended by guidelines for compensated transplant recipients. However, 12 weeks may not be the optimal duration of therapy for those with detectable virus at week 4 or possibly for those with cirrhosis. These data require confirmation by prospective randomized clinical trials. Liver Transplantation 22 635-643 2016 AASLD.

Impact of a Nursing Skill-Improvement Intervention on Newborn-Specific Delivery Practices: An Experience from Bihar, India.

BACKGROUND: High neonatal mortality in India had previously been attributed to the low proportion of institutional deliveries. However, a significant rise in the proportion of facility-based births over the last decade has not achieved the desired reduction in neonatal mortality possibly as a result of low-skilled care at facilities. This study evaluated the effectiveness of "Mobile Nurse Training," a knowledge-based intervention for nurses to improve essential newborn-specific delivery practices. METHODS: Eighty health centers with obstetric care facilities were selected from eight districts of Bihar. The intervention teams were composed of two trained nurses who conducted a week-long workshop per month at every health facility for 6 months. An independent evaluation team conducted baseline and postintervention assessments at every facility. The assessments included passive observation of newborn-specific delivery practices and recording of results on a preformatted checklist-based tool. RESULTS: The intervention was associated with significant increases in the odds of four recommended practices: placing the newborn on mother's abdomen (adjusted odds ratio (AOR) 4.2 [95% CI 3.0-5.9]), wiping the eyes with sterile gauze (AOR 2.2 [95% CI 1.4-3.4]), skin-to-skin care (AOR 2.7 [95% CI 2.0-3.5]), and guidance for initiation of breastfeeding (AOR 1.6 [95% CI 1.2-2.1]). The intervention was also found to be positively associated with the summary score for improvements in all newborn-specific delivery practices. One year after the intervention, the summary practice score remained higher than at baseline, but with some decline over time. CONCLUSIONS: The "Mobile Nurse Training" intervention provides a pathway for improving adherence to recommended newborn-specific delivery practices among institutional birth attendants in rural Bihar.

Long-term outcome of patients undergoing liver transplantation for mixed hepatocellular carcinoma and cholangiocarcinoma: an analysis of the UNOS database.

BACKGROUND: Mixed hepatocellular and cholangiocarcinoma (HCC-CC) have been associated with a poor prognosis after liver transplantation (LT). We aimed to evaluate long-term outcomes in patients undergoing LT for HCC-CC versus patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC). METHODS: Retrospective analysis of the United Network for Organ Sharing (UNOS) database from 1994-2013. Overall survival (OS) in patients with HCC-CC, HCC, and CC, were compared. RESULTS: We identified 4049 patients transplanted for primary malignancy (94 HCC-CC; 3515 HCC; 440 CC). Mean age of patients with HCC-CC was 57 ± 10 years, and 77% were male. MELD score did not differ among the groups (p = 0.637). Hepatitis C virus was the most common secondary diagnosis within the HCC-CC (44%) and HCC (36%) cohorts, with primary sclerosing cholangitis in the CC (16%) cohort. OS rates at 1, 3 and 5 years for HCC-CC (82%, 47%, 40%) were similar to CC (79%, 58%, 47%), but significantly worse than HCC (86%, 72%, and 62% p = 0.002). DISCUSSION: Patients undergoing LT for HCC had significantly better survival compared to those transplanted for HCC-CC and CC. LT for mixed HCC-CC confers a survival rate similar to selected patients with CC. Efforts should be made to identify HCC-CC patients preoperatively.

A prospective analysis of factors associated with decreased physical activity in patients with cirrhosis undergoing transplant evaluation.

BACKGROUND: Physical activity (PA) has been associated with improved recovery time after transplantation. Handgrip strength has been related to post-transplant outcomes. AIM: To evaluate predictors of PA and grip strength in patients with cirrhosis undergoing liver transplant evaluation. METHODS: Single-center, prospective analysis. RESULTS: One hundred patients were evaluated (54% male, mean age 53 ± 9). Common etiologies of liver disease were non-alcoholic steatohepatitis (27%), hepatitis C (22%) and alcoholic liver disease (21%). Mean model of end-stage liver disease (MELD) score was 13.5. Forty-one percent had a history of smoking. Ninety-three patients completed the International Physical Activity Questionnaire (IPAQ). The median total PA score was 33 metabolic equivalent (MET)-min/wk. The mean total grip strength was 62.1 ± 22 lb. Total grip strength was found to be an independent predictor of low-moderate PA (OR 4.7, 95% CI 1.4-16.2, p = 0.038), and smoking was the only significant factor associated with reduced grip strength (OR 3.4, 95% CI 1.4-8, p = 0.005). CONCLUSIONS: Patients with end-stage liver disease undergoing liver transplant evaluation have reduced total PA by IPAQ. Total grip strength was found to be a significant predictor of low-moderate PA in patients with cirrhosis. Smoking is a risk factor for reduced grip strength, an important indicator of muscle wasting in cirrhotics.

Liver Transplantation for Severe Hepatic Trauma: a multicenter analysis from the UNOS dataset.

BACKGROUND: Orthotopic liver transplantation (OLT) is rarely indicated after hepatic trauma but it can be the only therapeutic option in some patients. There are scarce data analyzing the surgical outcomes of OLT after trauma. METHODS: We used the UNOS dataset to identify patients who underwent OLT for trauma from 1987 to 2022, and compared them to a cohort of patients transplanted for other indications. Cox proportional hazard and multivariable logistic regression analyses were performed to assess predictors of graft and patient survival. RESULTS: 72 patients underwent OLT for trauma during the study period. Patients with trauma were more frequently on mechanical ventilation at the time of transplantation (26.4% vs. 7.6%, p < 0.001) and had a greater incidence of pre-transplant portal vein thrombosis (PVT) (12.5% vs. 4%, p = 0.002). Our 4:1 matched analysis showed that trauma patients had significantly shorter wait times, higher incidence of pre-transplant PVT and prolonged length of stay (LOS). Trauma was associated with decreased overall graft survival (HR = 1.42, 95% CI = 1.01-1.98), and increased LOS (p = 0.048). There were no significant differences in long term patient survival. CONCLUSION: Unique physiological and vascular challenges after severe hepatic trauma might be associated with decreased graft survival in patients requiring liver transplantation. LEVEL OF EVIDENCE: Retrospective cohort study, III.

Variability in Organ Procurement Organization Performance by Individual Hospital in the United States.

Importance: Availability of organs inadequately addresses the need of patients waiting for a transplant. Objective: To estimate the true number of donor patients in the United States and identify inefficiencies in the donation process as a way to guide system improvement. Design, Setting, and Participants: A retrospective cross-sectional analysis was performed of organ donation across 13 different hospitals in 2 donor service areas covered by 2 organ procurement organizations (OPOs) in 2017 and 2018 to compare donor potential to actual donors. More than 2000 complete medical records for decedents were reviewed as a sample of nearly 9000 deaths. Data were analyzed from January 1, 2017, to December 31, 2018. Exposure: Deaths of causes consistent with donation according to medical record review, ventilated patient referrals, center acceptance practices, and actual deceased donors. Main Outcomes and Measures: Potential donors by medical record review vs actual donors and OPO performance at specific hospitals. Results: Compared with 242 actual donors, 931 potential donors were identified at these hospitals. This suggests a deceased donor potential of 3.85 times (95% CI, 4.23-5.32) the actual number of donors recovered. There was a surprisingly wide variability in conversion of potential donor patients into actual donors among the hospitals studied, from 0% to 51.0%. One OPO recovered 18.8% of the potential donors, whereas the second recovered 48.2%. The performance of the OPOs was moderately related to referrals of ventilated patients and not related to center acceptance practices. Conclusions and Relevance: In this cross-sectional study of hospitals served by 2 OPOs, wide variation was found in the performance of the OPOs, especially at individual hospitals. Addressing this opportunity could greatly increase the organ supply, affirming the importance of recent efforts from the federal government to increase OPO accountability and transparency.