Beyond death and graft survival—Variation in outcomes after liver transplant. Results from the NSQIP transplant beta phase

The National Surgical Quality Program (NSQIP) Transplant program was designed by transplant surgeons from the ground up to track posttransplant outcomes beyond basic recipient and graft survival. After an initial pilot phase, the program has expanded to 29 participating sites and enrolled more than 4300 recipient‐donor pairs into the database, including 1444 completed liver transplant cases. In this analysis, surgical site infection (SSI), urinary tract infection (UTI), and unplanned reoperation/intervention after liver transplantation were evaluated. We observed impressive variation in the crude incidence between sites for SSI (0%‐29%), UTI (0%‐10%), and reoperation/intervention (0%‐57%). After adjustment for donor and recipient factors, at least 1 site was identified as an outlier for each of the analyzed outcomes. For the first time, the field of transplantation has data that demonstrate variation in liver recipient outcomes beyond death and graft survival between sites. More importantly, NSQIP Transplant provides a powerful platform to improve care beyond basic patient and graft survival.     

Intellectual and academic outcomes after pediatric liver transplantation: Relationship with transplant‐related factors

As survival rates for pediatric liver transplant continue to increase, research attention is turning toward long‐term functional consequences, with particular interest in whether medical and transplant‐related factors are implicated in neurocognitive outcomes. The relative importance of different factors is unclear, due to a lack of methodological uniformity, inclusion of differing primary diagnoses, varying transplant policies, and organ availability in different jurisdictions. This cross‐sectional, single‐site study sought to address various methodological limitations in the literature and the paucity of studies conducted outside of North America and Western Europe by examining the intellectual and academic outcomes of Australian pediatric liver transplant recipients (N = 40). Participants displayed significantly poorer intellectual and mathematical abilities compared with the normative population. Greater time on the transplant waitlist was a significant predictor of poorer verbal intelligence, working memory, mathematical abilities, and reading but only when considering the subgroup of children with biliary atresia. These findings support reducing the time children wait for a transplant as a priority.     

Living Donor Liver Transplantation for Patients Older Than Age 70 Years: A Single‐Center Experience

Over the past two decades, the age of liver transplantation (LT) recipients has been increasing. We reviewed our experience with LT for patients aged ≥70 years (range: 70–78 years) and investigated the feasibility of performing LT, especially living donor LT (LDLT), for older patients. We retrospectively reviewed the medical records of 25 patients (15 LDLT recipients, 10 deceased donor LT recipients) aged ≥70 years who underwent LT from January 2000 to April 2016. Their perioperative morbidity rate was 28.0%, and the in‐hospital mortality rate was 16.0%; these results were comparable to those of matched patients in their 60s (n = 73; morbidity, p = 0.726; mortality, p = 0.816). For patients in their 70s, the 1‐ and 5‐year patient survival rates were 84.0% and 69.8%, and the 1‐ and 5‐year graft survival rates were 83.5% and 75.1%, respectively. Comparisons of patient and graft survival rates between matched patients in their 60s and 70s showed no statistically significant differences (patient survival, p = 0.372; graft survival, p = 0.183). Our experience suggests that patients aged ≥70 years should not be excluded from LT, or even LDLT, based solely on age and implies that careful selection of recipients and donors as well as meticulous surgical technique are necessary for successful results.     

Waitlist Outcomes of Liver Transplant Candidates Who Were Reprioritized Under Share 35

Under Share 35, deceased donor (DD) livers are offered regionally to candidates with Model for End‐Stage Liver Disease (MELD) scores ≥35 before being offered locally to candidates with MELD scores <35. Using Scientific Registry of Transplant Recipients data from June 2013 to June 2015, we identified 1768 DD livers exported to regional candidates with MELD scores ≥35 who were transplanted at a median MELD score of 39 (interquartile range [IQR] 37–40) with 30‐day posttransplant survival of 96%. In total, 1764 (99.8%) exports had an ABO‐compatible candidate in the recovering organ procurement organization (OPO), representing 1219 unique reprioritized candidates who would have had priority over the regional candidate under pre–Share 35 allocation. Reprioritized candidates had a median waitlist MELD score of 31 (IQR 27–34) when the liver was exported. Overall, 291 (24%) reprioritized candidates had a comparable MELD score (within 3 points of the regional recipient), and 209 (72%) were eventually transplanted in 11 days (IQR 3–38 days) using a local (50%), regional (50%) or national (<1%) liver; 60 (21%) died, 13 (4.5%) remained on the waitlist and nine (3.1%) were removed for other reasons. Of those eventually transplanted, MELD score did not increase in 57%; it increased by 1–3 points in 37% and by ≥4 points in 5.7% after the export. In three cases, OPOs exchanged regional exports within a 24‐h window. The majority of comparable reprioritized candidates were not disadvantaged; however, 21% died after an export.     

National Healthcare Delivery Systems Influence Lung Transplant Outcomes for Cystic Fibrosis

Successful lung transplantation (LTx) depends on multiple components of healthcare delivery and performance. Therefore, we conducted an international registry analysis to compare post‐LTx outcomes for cystic fibrosis (CF) patients using the UNOS registry in the United States and the National Health Service (NHS) Transplant Registry in the United Kingdom. Patients with CF who underwent lung or heart–lung transplantation in the United States or United Kingdom between January 1, 2000 and December 31, 2011 were included. The primary outcome was all‐cause mortality. Kaplan–Meier analysis and Cox proportional hazards regression evaluated the effect of healthcare system and insurance on mortality after LTx. 2,307 US LTx recipients and 451 individuals in the United Kingdom were included. 894 (38.8%) US LTx recipients had publically funded Medicare/Medicaid insurance. US private insurance and UK patients had improved median predicted survival compared with US Medicare/Medicaid recipients (p < 0.001). In multivariable Cox regression, US Medicare/Medicaid insurance was associated with worse survival after LTx (US private: HR0.78,0.68–0.90,p = 0.001 and UK: HR0.63,0.41–0.97, p = 0.03). This study in CF patients is the largest comparison of LTx in two unique health systems. Both the United States and United Kingdom have similar early survival outcomes, suggesting important dissemination of best practices internationally. However, the performance of US public insurance is significantly worse and may put patients at risk.     

First‐Degree Living‐Related Donor Liver Transplantation in Autoimmune Liver Diseases

Liver transplantation (LT) is the treatment of choice for end‐stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first‐degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty‐three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post‐LT follow‐up, were included in this study. Of these, 72 (27%) received a graft from a first‐degree living‐related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first‐degree living‐related, living‐unrelated, or deceased‐donor LT. Similarly, time to recurrence, recurrence‐related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first‐degree living‐related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.     

Liver transplantation in the United States during the COVID-19 pandemic: National and center-level responses

COVID-19 has profoundly affected the American health care system; its effect on the liver transplant (LT) waitlist based on COVID-19 incidence has not been characterized. Using SRTR data, we compared observed LT waitlist registrations, waitlist mortality, deceased donor LTs (DDLT), and living donor LTs (LDLT) 3/15/2020-8/31/2020 to expected values based on historical trends 1/2016-1/2020, stratified by statewide COVID-19 incidence. Overall, from 3/15 to 4/30, new listings were 11% fewer than expected (IRR = _0.84 0.89_0.93), LDLTs were 49% fewer (IRR = _0.37 0.51_0.72), and DDLTs were 9% fewer (IRR = _0.85 0.91_0.97). In May, new listings were 21% fewer (IRR = _0.74 0.79_0.84), LDLTs were 42% fewer (IRR = _0.39 0.58_0.85) and DDLTs were 13% more (IRR = _1.07 1.15_1.23). Centers in states with the highest incidence 3/15-4/30 had 59% more waitlist deaths (IRR = _1.09 1.59_2.32) and 34% fewer DDLTs (IRR = _0.50 0.66_0.86). By August, waitlist outcomes were occurring at expected rates, except for DDLT (13% more across all incidences). While the early COVID-affected states endured major transplant practice changes, later in the pandemic the newly COVID-affected areas were not impacted to the same extent. These results speak to the adaptability of the transplant community in addressing the pandemic and applying new knowledge to patient care.     

Retransplantation outcomes for hepatitis C in the United States before and after direct-acting antiviral introduction

The success of direct-acting antiviral (DAA) therapy has led to near-universal cure for patients chronically infected with hepatitis C virus (HCV) and improved post–liver transplant (LT) outcomes. We investigated the trends and outcomes of retransplantation in HCV and non-HCV patients before and after the introduction of DAA. Adult patients who underwent re-LT were identified in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Multiorgan transplants and patients with >2 total LTs were excluded. Two eras were defined: pre-DAA (2009-2012) and post-DAA (2014-2017). A total of 2112 re-LT patients were eligible (HCV: n = 499 pre-DAA and n = 322 post-DAA; non-HCV: n = 547 pre-DAA and n = 744 post-DAA). HCV patients had both improved graft and patient survival after re-LT in the post-DAA era. One-year graft survival was 69.8% pre-DAA and 83.8% post-DAA (P < .001). One-year patient survival was 73.1% pre-DAA and 86.2% post-DAA (P < .001). Graft and patient survival was similar between eras for non-HCV patients. When adjusted, the post-DAA era represented an independent positive predictive factor for graft and patient survival (hazard ratio [HR]: 0.67; P = .005, and HR: 0.65; P = .004) only in HCV patients. The positive post-DAA era effect was observed only in HCV patients with first graft loss due to disease recurrence (HR: 0.31; P = .002, HR 0.32; P = .003, respectively). Among HCV patients, receiving a re-LT in the post-DAA era was associated with improved patient and graft survival.     

Dual‐graft adult living donor liver transplantation with ABO‐incompatible graft: short‐term and long‐term outcomes

ABO‐incompatible (ABOi) dual‐graft (DG) adult living donor liver transplantation (ALDLT) is not commonly performed due to its inherently intricate surgical technique and immunological complexity. Therefore, data are lacking on the short‐ and long‐term clinical outcomes of ABOi DG ALDLT. We performed a retrospective study by reviewing the medical records of patients who underwent ABOi DG ALDLT between 2008 and 2014. Additionally, computed tomography volumetric analysis was conducted to assess the graft regeneration rate. The mean age of a total of 28 recipients was 50.2 ± 8.5 years, and the mean model for end‐stage liver disease score was 12.2 ± 4.6. The 1‐, 3‐, and 5‐year patient survival rate was 96.4% during the mean follow‐up period of 57.0 ± 22.4 months. The 1‐, 3‐, and 5‐year graft survival rate was 96.4%, 94.2%, and 92.0%, respectively, and no significant differences were observed between ABO‐compatible (ABOc) and ABOi grafts (P = .145). The biliary complication rate showed no significant difference (P = .195) between ABOc and ABOi grafts. Regeneration rates of ABOi grafts were not significantly different from those of ABOc grafts. DG ALDLT with ABOi and ABOc graft combination seems to be a feasible option for expanding the donor pool without additional donor risks.     

Hepatic encephalopathy impacts the predictive value of the Fried Frailty Index

Frailty is increasingly recognized as a predictor of poor outcomes in solid organ transplantation. The most widely utilized frailty tool, the Fried Frailty Index (FFI), includes patient‐reported exhaustion, weight loss, and physical activity as well as measured walk speed and handgrip. Although hepatic encephalopathy (HE) is common among liver transplant candidates, data are lacking regarding its impact on the interpretation of frailty. We prospectively enrolled 685 patients with cirrhosis during their transplant evaluation, following them until death or transplantation. Our cohort was aged 54.5 ± 10.3 years, 60% male, with an average MELD score of 14.7 ± 6.3. A history of HE was present in 39%. Frailty was present in 41%, associated with higher MELD, low albumin, ascites, and HE. HE was associated with frail performance on three components of the FFI‐grip (odds ratio 1.41 95% CI, 1.03‐1.92), walk speed (1.56 95% CI, 1.14‐2.15), and decreased energy (1.44 95% CI, 1.05‐1.99). These three components were associated with transplant free survival in the whole cohort: energy (hazard ratio 1.67 95% CI, 1.25‐2.28), grip (1.63 95% CI, 1.24‐2.16), and walk speed (1.56 95% CI, 1.19‐2.04). However, among patients with HE, the FFI was not associated with survival. HE plays a critical role in the frailty phenotype and the implications of frailty among patients with cirrhosis evaluated for liver transplantation.     

Patient‐reported outcome measures for life participation in kidney transplantation: A systematic review

For many patients with end‐stage kidney disease, transplantation improves survival and quality of life compared with dialysis. However, complications and side effects in kidney transplant recipients can limit their ability to participate in activities of daily living including work, study, and recreational activities. The aim of this study was to identify the characteristics, content, and psychometric properties of the outcome measures used to assess life participation in kidney transplant recipients. We searched MEDLINE, Embase, PsycINFO, and CINAHL from inception to July 2018 for all studies that reported life participation in kidney transplant recipients. Two authors identified instruments measuring life participation and reviewed for characteristics. In total, 230 studies were included: 19 (8%) randomized trials, 17 (7%) nonrandomized trials, and 194 (85%) observational studies. Across these studies, we identified 29 different measures that were used to assess life participation. Twelve (41%) measures specifically assessed aspects of life participation (eg, disability assessment, daily activities of living), while 17 (59%) assessed other constructs (eg, quality of life) that included questions on life participation. Validation data to support the use of these measures in kidney transplant recipients were available for only 7 measures. A wide range of measures have been used to assess life participation in kidney transplant recipients, but validation data supporting the use of these measures in this population are sparse. A content relevant and validated measure to improve the consistency and accuracy of measuring life participation in research may inform strategies for transplant recipients to be better able to engage in their life activities.     

Patient‐reported health outcomes in long‐term lung transplantation survivors: A prospective cohort study

During the last three decades lung transplantation (LTx) has become a proven modality for increasing both survival and health‐related quality of life (HRQoL) in patients with various end‐stage lung diseases. Most previous studies have reported improved HRQoL shortly after LTx. With regard to long‐term effects on HRQoL, however, the evidence is less solid. This prospective cohort study was started with 828 patients who were on the waiting list for LTx. Then, in a longitudinal follow‐up, 370 post‐LTx patients were evaluated annually for up to 15 years. For all wait‐listed and follow‐up patients, the following four HRQoL instruments were administered: State‐Trait Anxiety Inventory, Zung Self‐rating Depression Scale, Nottingham Health Profile, and a visual analogue scale. Cross‐sectional and generalized estimating equation (GEE) analysis for repeated measures were performed to assess changes in HRQoL during follow‐up. After LTx, patients showed improvement in all HRQoL domains except pain, which remained steady throughout the long‐term follow‐up. The level of anxiety and depressive symptoms decreased significantly and remained constant. In conclusion, this study showed that HRQoL improves after LTx and tends to remain relatively constant for the entire life span.     

Blood pressure control according to clinical practice guidelines is associated with decreased mortality and cardiovascular events among liver transplant recipients

Data for liver transplant recipients (LTRs) regarding the benefit of care concordant with clinical practice guidelines for management of blood pressure (BP) are sparse. This paper reports on clinician adherence with BP clinical practice guideline recommendations and whether BP control is associated with mortality and cardiovascular events (CVEs) among LTRs. We conducted a longitudinal cohort study of adult LTRs who survived to hospital discharge at a large tertiary care network between 2010 and 2016. The primary exposure was a BP of <140/<90 mm Hg within year 1 of LT. Among 602 LTRs (mean age 56.7 years, 64% men), 92% had hypertension and 38% had new onset hypertension. Less than 30% of LTRs achieved a BP of <140/<90 mm Hg over a mean of 43.2 months. In multivariable models, adjusted for key confounders, BP control post‐LT compared with lack of control was associated with a significantly lower hazard of mortality (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.39, 0.87) and of CVEs (HR 0.65, 95% CI 0.43, 0.97). The association between BP control of <140/<90 mm Hg with improved survival and decreased CVEs in LTRs suggests that efforts to improve clinician adherence to BP clinical practice recommendations should be intensified.