Survival following liver transplantation: A population-based nested case-control study.

BACKGROUND: Liver transplantation is the gold standard treatment for end-stage liver disease. This study evaluates post-transplantation survival compared with the general population by quantifying standardized mortality ratios in a nested case-control study. METHODS: Controls were noninstitutionalized United States inhabitants from the National Longitudinal Mortality Study. Cases underwent liver transplantation from 1990 to 2007 identified through the Organ Procurement and Transplantation Network database. Propensity matching (5:1, nearest neighbor, caliper 0.1) identified controls based on age, sex, race, and state. The primary endpoint was 10-year survival. RESULTS: 62,788 cases were matched to 313,381 controls. The overall standardized mortality ratio was 2.46 (95% CI â€‹= â€‹2.44-2.48). The standardized mortality ratio was higher for males (2.59 vs. 2.25) and Hispanic patients (4.80). Younger patients and those transplanted earlier (1990-1995) had higher standardized mortality ratios. CONCLUSIONS: Liver recipients have a standardized mortality ratio 2.46 times higher than the general population. Long-term mortality has declined over time.

Sleeve Gastrectomy Reduces the Need for Liver Transplantation in Patients with Obesity and Non-Alcoholic Steatohepatitis: a Predictive Model.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is one of the leading indications for liver transplantation (LT) in the United States. As with the current obesity epidemic, the incidence of NASH continues to rise. However, the impact of broad utilization of bariatric surgery (BS) for patients with NASH is unknown, particularly in regard to mitigating the need for LT. METHODS: Markov decision analysis was performed to simulate the lives of 20,000 patients with obesity and concomitant NASH who were deemed ineligible to be waitlisted for LT unless they achieved a body mass index (BMI) < 35 kg/m2. Life expectancy following medical weight management (MWM) and sleeve gastrectomy (SG) were estimated. Base case patients were defined as having NASH without fibrosis and a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. RESULTS: Simulated base case analysis patients who underwent SG gained 14.3 years of life compared to patients who underwent MWM. One year after weight loss intervention, 9% of simulated MWM patients required LT compared to only 5% of SG patients. Survival benefit for SG was observed above a BMI of 32.2 kg/m2. CONCLUSION: In this predictive model of 20,000 patients with obesity and concomitant NASH, surgical weight loss is associated with a reduction in the progression of NASH, thereby reducing the need for LT. A reduced BMI threshold of 32 kg/m2 for BS may offer survival benefit for patients with obesity and NASH.

Ventricular Remodeling Following Metabolic and Bariatric Surgery Decreases Need for Heart Transplantation: A Predictive Model.

PURPOSE: For patients with obesity and congestive heart failure (CHF) who require heart transplantation (HT), aggressive weight loss has been associated with ventricular remodeling, or subclinical alterations in left and right ventricular structure that affect systolic function. Many have suggested offering metabolic and bariatric surgery (MBS) for these patients. As such, we evaluated the role of MBS in HT for patients with obesity and CHF using predictive modelling techniques. MATERIALS AND METHODS: Markov decision analysis was performed to simulate the life expectancy of 30,000 patients with concomitant obesity, CHF, and 30% ejection fraction (EF) who were deemed ineligible to be waitlisted for HT unless they achieved a BMI < 35 kg/m2. Life expectancy following diet and exercise (DE), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) was estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. RESULTS: RYGB patients had lower rates of HT and received HT quicker when needed. Base case patients who underwent RYGB gained 2.2 additional mean years survival compared with patients who underwent SG and 10.3 additional mean years survival compared with DE. SG patients gained 6.2 mean years of life compared with DE. CONCLUSION: In this simulation of 30,000 patients with obesity, CHF, and reduced EF, MBS was associated with improved survival by not only decreasing the need for transplantation due to improvements in EF, but also increasing access to HT when needed due to lower average BMI.

Uncontrolled donation after cardiac death kidney transplantation: Opportunity to expand the donor pool?

BACKGROUND: Compared to controlled donation after cardiac death (cDCD), uncontrolled DCD (uDCD) kidney transplantation remains an underutilized resource in the United States. However, it is unclear whether long-term allograft outcomes following uDCD are inferior to that of cDCD kidney transplantation. METHODS: From January 1995 to January 2018, the OPTN/UNOS database was queried to discover all reported cases of uDCD and cDCD kidney transplantation. Primary non-function, delayed graft function, ten-year graft and patient survival were compared among uDCD and cDCD patients. RESULTS: Rates of primary non-function (4.0% [uDCD] vs. 1.8% [cDCD], P < 0.001) and delayed graft function (51.1% [uDCD] vs. 41.7% [cDCD], P < 0.001) were higher following uDCD transplant. However, ten-year graft survival (47.5% [uDCD] vs. 48.4% [cDCD], P = 0.21) and patient survival were similar to cDCD transplantation (59.4% [uDCD] vs. 59.2% [cDCD], P = 0.32). CONCLUSION: Although initial allograft outcomes are inferior following uDCD, long-term durability of uDCD kidney allografts is on par to cDCD transplantation. Kidney allografts derived by uDCD may be a viable and durable option to increase the donor pool.

Quality and readability of online patient information on the left ventricular assist device.

BACKGROUND: As patients seek online health information to supplement their medical decision-making, the aim of this study is to assess the quality and readability of internet information on the left ventricular assist device (LVAD). METHODS: Three online search engines (Google, Bing, and Yahoo) were searched for "LVAD" and "Left ventricular assist device." Included websites were classified as academic, foundation/advocacy, hospital-affiliated, commercial, or unspecified. The quality of information was assessed using the JAMA benchmark criteria (0-4), DISCERN tool (16-80), and the presence of Health On the Net code (HONcode) accreditation. Readability was assessed using the Flesch Reading Ease score. RESULTS: A total of 38 unique websites were included. The average JAMA and DISCERN scores of all websites were 0.82 ± 1.11 and 52.45 ± 13.51, respectively. Academic sites had a significantly lower JAMA mean score than commercial (p < 0.001) and unspecified (p < 0.001) websites, as well as a significantly lower DISCERN, mean score than commercial sites (p = 0.002). HONcode certification was present in 6 (15%) websites analyzed, which had significantly higher JAMA (p < 0.001) and DISCERN (p < 0.016) mean scores than sites without HONcode certification. Readability was fairly difficult and at the level of high school students. CONCLUSIONS: The quality of online information on the LVAD is variable, and overall readability exceeds the recommended level for the public. Patients accessing online information on the LVAD should be referred to sites with HONcode accreditation. Academic institutions must provide higher quality online patient literature on LVADs.

Can non-directed living liver donation help improve access to grafts and correct socioeconomic disparities in pediatric liver transplantation?

BACKGROUND: Each year, children die awaiting LT as the demand for grafts exceeds the available supply. Candidates with public health insurance are significantly less likely to undergo both deceased donor LT and D-LLD LT. ND-LLD is another option to gain access to a graft. The aim of this study was to evaluate if recipient insurance type is associated with likelihood of D-LLD versus ND-LLD LT. METHODS: The SRTR/OPTN database was reviewed for pediatric LDLT performed between January 1, 2014 (Medicaid expansion era) and December 31, 2019 at centers that performed ≥1 ND-LLD LDLT during the study period. A multivariable logistic regression was performed to assess relationship between type of living donor (directed vs. non-directed) and recipient insurance. RESULTS: Of 299 pediatric LDLT, 46 (15%) were from ND-LLD performed at 18 transplant centers. Fifty-nine percent of ND-LLD recipients had public insurance in comparison to 40% of D-LLD recipients (p = .02). Public insurance was associated with greater odds of ND-LLD in comparison to D-LLD upon multivariable logistic regression (OR 2.37, 95% CI 1.23-4.58, p = .01). CONCLUSIONS: ND-LLD allows additional children to receive LTs and may help address some of the socioeconomic disparity in pediatric LDLT, but currently account for only a minority of LDLT and are only performed at a few institutions. Initiatives to improve access to both D-LLD and ND-LLD transplants are needed.

Surgical Treatment of Short Bowel Syndrome-The Past, the Present and the Future, a Descriptive Review of the Literature.

Short bowel syndrome (SBS) is a devastating disorder with both short- and long-term implications for patients. Unfortunately, the prevalence of SBS has doubled over the past 40 years. Broadly speaking, the etiology of SBS can be categorized as congenital or secondary, the latter typically due to extensive small bowel resection following diseases of the small intestine, e.g., necrotizing enterocolitis, Hirschsprung's disease or intestinal atresia. As of yet, no cure exists, thus, conservative treatment, primarily parenteral nutrition (PN), is the first-line therapy. In some cases, weaning from PN is not possible and operative therapy is required. The invention of the longitudinal intestinal lengthening and tailoring (LILT or Bianchi) procedure in 1980 was a major step forward in patient care and spawned further techniques that continue to improve lives for patients with severe SBS (e.g., double barrel enteroplasty, serial transverse enteroplasty, etc.). With this review, we aim to provide an overview of the clinical implications of SBS, common conservative therapies and the development of operative techniques over the past six decades. We also provide a short outlook on the future of operative techniques, specifically with respect to regenerative medicine.

Living Donor Liver Transplant Center Volume Influences Waiting List Survival Among Children Listed for Liver Transplantation.

BACKGROUND: Pediatric living donor liver transplantation (LDLT) remains infrequently performed in the United States and localized to a few centers. This study aimed to compare pediatric waiting list and posttransplant outcomes by LDLT center volume. METHODS: The Scientific Registry of Transplant Recipients/Organ Procurement and Transplantation Network database was retrospectively reviewed for all pediatric (age <18 y) liver transplant candidates listed between January 1, 2009, and December 31, 2019. The average annual number of LDLT, deceased donor partial liver transplant (DDPLT), and overall (ie, LDLT + DDPLT + whole liver transplants) pediatric liver transplants performed by each transplant center during the study period was calculated. RESULTS: Of 88 transplant centers, only 44 (50%) performed at least 1 pediatric LDLT during the study period. LDLT, DDPLT, and overall transplant center volume were all positively correlated. LDLT center volume was protective against waiting list dropout after adjusting for confounding variables (adjusted hazard ratio, 0.92; 95% confidence interval, 0.86-0.97; P = 0.004), whereas DDPLT and overall center volume were not ( P > 0.05); however, DDPLT center volume was significantly protective against both recipient death and graft loss, whereas overall volume was only protective against graft loss and LDLT volume was not protective for either. CONCLUSIONS: High-volume pediatric LDLT center can improve waiting list survival, whereas DDPLT and overall volume are associated with posttransplant survival. Expertise in all types of pediatric liver transplant options is important to optimize outcomes.

The vexing triad of obesity, alcohol, and coagulopathy predicts the need for multiple operations in liver transplantation.

INTRODUCTION: One in four liver transplants (LT) require return to the operating room(R-OR) within 48 h of surgery. We hypothesize that donor, recipient, and intraoperative factors will predict R-OR. METHODS: LT recipients were enrolled in an observational study to measure coagulation with thrombelastography (TEG) were assessed with transplant recipient and donor variables for risk of R-OR. RESULTS: 160 recipients with a median age of 55 years and a MELD-Na of 22 were analyzed. R-OR occurred in 22%. Recipient BMI (p = 0.006), donor heavy alcohol use (p = 0.017), TEG MA (p = 0.013) during the anhepatic phase of surgery, TEG MA at anhepatic and 30-min after reperfusion (p < 0.05), and red blood cell transfusions (p < 0.001) were associated with R-OR. CONCLUSION: The vexing triad of recipient obesity, heavy donor alcohol use, and low TEG MA were associated with a high rate of R-OR. Strategies to reduce this sub-optimal combination of risk factors could reduce the frequency of unplanned re-operations.

Primary vs. salvage liver transplantation for biliary atresia: A retrospective cohort study.

INTRODUCTION: Kasai hepatoportoenterostomy is the standard of care for children with biliary atresia, but a majority of patients progress to end-stage liver disease and require a salvage liver transplant. Given the high failure rates of the hepatoportoenterostomy operation, some have advocated for primary liver transplantation as a superior treatment approach. The aim of this study was to compare outcomes of pediatric candidates with biliary atresia listed for primary vs. salvage liver transplantation. METHODS: The SRTR/OPTN database was retrospectively reviewed for all children with biliary atresia listed for liver transplant between March 2002 and February 2021. Candidates were categorized as primary liver transplant if they had not undergone previous abdominal surgery prior to listing and salvage liver transplant if they had. Salvage transplants were further categorized as early failure if listed within the first year of life or late failure if listed at an older age. RESULTS: 3438 children with biliary atresia were listed for transplant during the study period, with 15% of them listed for a primary transplant, 17% for salvage transplant after early failure, and 67% after late failure. Recipients of salvage liver transplant with late failure had lower bilirubin levels and were less critically ill as demonstrated by MELD/PELD scores and hospitalization status. Correspondingly, these recipients had higher waiting list and graft survival, though this did not remain statistically significant after adjustment in multivariable models. There were no differences in waiting list, recipient, or graft survival with primary vs. salvage liver transplant after early failure. CONCLUSION: Kasai hepatoportoenterostomy should remain the standard of care in biliary atresia as it may delay need for transplant beyond the first year of life in a subset of recipients and does not jeopardize subsequent transplant outcomes, even with early failure. LEVELS OF EVIDENCE: Retrospective cohort study (Level III).

Measuring the effect of the COVID-19 pandemic on solid organ transplantation.

BACKGROUND: The COVID-19 pandemic has uniquely affected the United States. We hypothesize that transplantation would be uniquely affected. METHODS: In this population-based cohort study, adult transplantation data were examined as time series data. Autoregressive-integrated-moving-average models of transplantation rates were developed using data from 1990 to 2019 to forecast the 2020 expected rates in a theoretical scenario if the pandemic did not occur to generate observed-to-expected (O/E) ratios. RESULTS: 32,594 transplants were expected in 2020, and only 30,566 occurred (O/E 0.94, CI 0.88-0.99). 58,152 waitlist registrations were expected and 50,241 occurred (O/E 0.86, CI 0.80-0.94). O/E ratios of transplants were kidney 0.92 (0.86-0.98), liver 0.96 (0.89-1.04), heart 1.05 (0.91-1.23), and lung 0.92 (0.82-1.04). O/E ratios of registrations were kidney 0.84 (0.77-0.93), liver 0.95 (0.86-1.06), heart 0.99 (0.85-1.18), and lung 0.80 (0.70-0.94). CONCLUSIONS: The COVID-19 pandemic was associated with a significant deficit in transplantation. The impact was strongest in kidney transplantation and waitlist registration.

Are Hepatitis C Positive Female Liver Transplant Recipients Still at Increased Risk for Graft Failure? Reexamining the Disparity in the Modern Era of Direct-acting Antiviral Agents.

BACKGROUND: This study aimed to compare the outcomes of hepatitis C virus (HCV) positive (+) female liver transplant recipients to HCV negative (-) female and HCV+ male recipients before and after the direct-acting-antiviral (DAA) era. METHODS: The United Network for Organ Sharing liver transplant database was retrospectively reviewed from 2002 to 2017. The DAA era was defined as ≥2014. RESULTS: In the pre-DAA era, HCV+ female recipients had greater risk for graft failure compared with HCV+ male (hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01-1.11; P = 0.03) and HCV- female (HR, 1.51; 95% CI, 1.43-1.60; P < 0.001) recipients. In the post-DAA era, HCV+ female recipients had lower risk for graft failure compared with HCV+ male recipients (HR, 0.82; 95% CI, 0.70-0.97; P = 0.02) and equivalent outcomes to HCV- female recipients. HCV+ female recipients with graft failure had increased likelihood of graft failure due to disease recurrence compared with HCV+ male recipients in the pre-DAA era (odds ratio, 1.23; 95% CI, 1.08-1.39; P = 0.001) but not in the post-DAA era. CONCLUSIONS: Although historically HCV+ female recipients were at disproportionately increased risk for graft failure and disease recurrence, this disparity has been eliminated in the DAA era.

Corrigendum: Microbial Colonization From the Fetus to Early Childhood-A Comprehensive Review.

[This corrects the article DOI: 10.3389/fcimb.2020.573735.].

Challenging the Traditional Paradigm of Supply and Demand in Pediatric Liver Transplantation Through Nondirected Living Donation: A Case Series.

A gap exists between the demand for pediatric liver transplantation and the supply of appropriate size-matched donors. We describe our center's experience with pediatric liver transplantation using anonymous nondirected living liver donors (ND-LLD). First-time pediatric liver transplant candidates listed at our center between January 2012 and June 2020 were retrospectively reviewed and categorized by donor graft type, and recipients of ND-LLD grafts were described. A total of 13 ND-LLD pediatric liver transplantations were performed, including 8 left lateral segments, 4 left lobes, and 1 right lobe. Of the ND-LLD recipients, 5 had no directed living donor evaluated, whereas the remaining 8 (62%) had all potential directed donors ruled out during the evaluation process. Recipient and graft survival were 100% during a median follow-up time of 445 (range, 70-986) days. Of ND-LLDs, 69% were previous living kidney donors, and 1 ND-LLD went on to donate a kidney after liver donation. Of the ND-LLDs, 46% were approved prior to the recipient being listed. Over time, the proportion of living donor transplants performed, specifically from ND-LLDs, increased, and the number of children on the waiting list decreased. The introduction of ND-LLDs to a pediatric liver transplant program can expand the benefit of living donor liver transplantation to children without a suitable directed living donor while achieving excellent outcomes for both the recipients and donors.

Bariatric Surgery for Congestive Heart Failure Patients Improves Access to Transplantation and Long-term Survival.

INTRODUCTION: Obese patients with congestive heart failure (CHF) are often denied access to heart transplantation until they obtain significant weight loss to achieve a certain BMI threshold, often less than 35 kg/m2. It is unknown whether the rapid weight loss associated with bariatric surgery leads to improved waitlist placement, and as such improved survival for morbidly obese patients with CHF. METHODS: A decision analytic Markov state transition model was created to simulate the life of morbidly obese patients with CHF who were deemed ineligible to be waitlisted for heart transplantation unless they achieved a BMI less than 35 kg/m2. Life expectancy following medical weight management (MWM), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) was estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. Markov parameters were extracted from literature review. RESULTS: RYGB improved survival compared with both SG and MWM. RYGB patients had higher rates of transplantation, leading to improved mean long-term survival. Base case patients who underwent RYGB gained 2.1 additional years of life compared with patient's who underwent SG and 7.4 additional years of life compared with MWM. SG patients gained 5.3 years of life compared with MWM. CONCLUSIONS: When strict waitlist criteria were applied, bariatric surgery improved access to heart transplantation and thereby increased long-term survival compared with MWM. Morbidly obese CHF patients who anticipate need for heart transplantation should be encouraged to pursue surgical weight management strategies, necessitating discussion between bariatric surgeons, cardiologists, and cardiac surgeons for appropriate perioperative risk management.

The Surge in Deceased Liver Donors Due to the Opioid Epidemic: Is It Time to Split the Difference?

BACKGROUND: This study aimed to compare trends in use of drug overdose (DO) donors in adult versus pediatric liver transplants and the utilization of split liver transplantation in this donor population. METHODS: The United Network for Organ Sharing database was reviewed for deceased donor liver transplants from March 2002 to December 2017. Recipients were categorized by donor mechanism of death. Donor splitting criteria was defined as age <40 y, single vasopressor or less, transaminases no >3 times the normal limit, and body mass index ≤ 28 kg/m2. RESULTS: Adult liver transplants from DO donors increased from 2% in 2002 to 15% in 2017, while pediatric liver transplants from DO donors only increased from <1% to 3% in the same time. While 28% of DO donors met splitting criteria, only 3% of those meeting splitting criteria were used as a split graft. Both pediatric and adult recipients of DO donor livers achieved excellent patient and graft survival. CONCLUSIONS: DO donors are underutilized in pediatric liver transplantation. Increased splitting of DO donor livers could significantly decrease, if not eliminate, the pediatric liver waiting list.

Microbial Colonization From the Fetus to Early Childhood-A Comprehensive Review.

The development of the neonatal gastrointestinal tract microbiota remains a poorly understood process. The interplay between neonatal (gestational age, genetic background), maternal (mode of delivery, nutritional status) and environmental factors (antibiotic exposure, available nutrition) are thought to influence microbial colonization, however, the exact mechanisms are unclear. Derangements in this process likely contribute to various gastrointestinal diseases including necrotizing enterocolitis and inflammatory bowel disease. As such, enhanced understanding of microbiota development may hold the key to significantly reduce the burden of gastrointestinal disease in the pediatric population. The most debatable topics during microbial seeding and possible future treatment approaches will be highlighted in this review.