Mortality among solid organ waitlist candidates during COVID-19 in the United States

We examined the effects of COVID-19 on solid organ waiting list mortality in the United States and compared effects across patient demographics (e.g., race, age, and sex) and donation service areas. Three separate piecewise exponential survival models estimated for each solid organ the overall, demographic-specific, and donation service area-specific differences in the hazard of waitlist mortality before and after the national emergency declaration on March 13, 2020. Kidney waiting list mortality was higher after than before the national emergency (adjusted hazard ratio [aHR], 1.37; 95% CI, 1.23–1.52). The hazard of waitlist mortality was not significantly different before and after COVID-19 for liver (aHR, 0.94), pancreas (aHR, 1.01), lung (aHR, 1.00), and heart (aHR, 0.94). Kidney candidates had notable variability in differences across donation service areas (aHRs, New York City, 2.52; New Jersey, 1.84; and Michigan, 1.56). The only demographic group with increased waiting list mortality were Blacks versus Whites (aHR, 1.41; 95% CI, 1.07–1.86) for kidney candidates. The first 10 weeks after the declaration of a national emergency had a heterogeneous effect on waitlist mortality rate, varying by geography and ethnicity. This heterogeneity will complicate comparisons of transplant program performance during COVID-19.     

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 transplant for hepatocellular carcinoma in the United States: Evolving trends over the last three decades

Hepatitis C virus infection has been the most common etiology in HCC‐related liver transplantation (LT). Since 2014, direct‐acting antivirals (DAAs) have dramatically improved HCV cure. We aimed to study the changing pattern of etiologies and impact in outcome in HCC‐related LT according to HCV treatment‐era through retrospective analysis of the Scientific Registry of Transplant Recipients (SRTR) database (1987‐2017). A total of 27 855 HCC‐related liver transplants were performed (median age 59 years, 77% male). In the DAA era (2014‐2017) there has been a 14.6% decrease in LT for HCV‐related HCC; however, HCV remains the most common etiology in 50% of cases. In the same era, there has been a 50% increase in LT for NAFLD‐related HCC. Overall survival was significantly worse for HCV‐related HCC compared to NAFLD‐related HCC during pre‐DAA era (2002‐2013; P = .031), but these differences disappeared in the DAA era. In addition, HCV patients had a significant improvement in survival when comparing the DAA era with IFN era (P < .001). Independent predictors of survival were significantly different in the pre‐DAA era (HCV, AFP, diabetes) than in the DAA era (tumor size). HCV‐related HCC continues to be the main indication for LT in the DAA era, but patients’ survival has significantly improved and is comparable to that of NAFLD‐related HCC.     

Sociodemographic Determinants of Waitlist and Posttransplant Survival Among End‐Stage Liver Disease Patients

While regional organ availability dominates discussions of distribution policy, community‐level disparities remain poorly understood. We studied micro‐geographic determinants of survival risk and their distribution across Donor Service Areas (DSAs). Scientific Registry of Transplant Recipients records for all adults waitlisted for liver transplantation 2002–2014 were reviewed. The primary exposure variables were county‐level sociodemographic risk, as measured by the Community Health Score (CHS), a previously‐validated composite index local health conditions, and distance to listing transplant center. Among 114 347 patients, the median CHS was 19.4 (range: 0–40). Compared the lowest risk counties (CHS 1–10), highest‐risk counties (CHS 31–40) had more black (14.6% vs. 5.4%), publicly insured (44.9% vs. 33.0), and remote candidates (34.0% vs. 15.1% living >100 miles away). Higher‐CHS candidates had greater waitlist mortality in Cox multivariable (HR 1.16 for CHS 31–40, 95% CI 1.11–1.21) and competing risks analysis (sHR 1.07, 95% CI 0.99–1.14). Post‐transplant survival was similar across CHS quartiles. Living >25 miles from the transplant center conferred excess mortality risk (sHR 1.08, 95% CI 1.03–1.12). Proposed distribution changes would disproportionately impact DSAs with more high‐CHS or distant candidates. Low‐income, rural and minority patients experience excess mortality while awaiting transplant, and risk disproportionately worse outcomes with reduced organ availability under current proposals.     

ABO‐Nonidentical Liver Transplantation in the United States

Under the United Network for Organ Sharing (UNOS) policy, deceased donor livers may be offered to ABO‐nonidentical candidates at each given Model for End‐Stage Liver Disease (MELD) score and to blood type B candidates at MELD ≥30. To evaluate ABO‐nonidentical liver transplantation (LT) in the United States, we examined all adult LT non–status 1 candidates, recipients and deceased liver donors from 2013 to 2015. There were 34 920 LT candidates (47% type O, 38% type A, 12% type B, 3% type AB) and 10 479 deceased liver donors (47% type O, 38% type A, 12% type B, 3% type AB). ABO‐nonidentical LT occurred in 2%, 3%, 20% and 36% of types O, A, B and AB recipients, respectively, which led to a net liver loss of 6% for type O and 2% for type A recipients but a net liver gain of 14% for type B and 55% for type AB recipients. The LT MELD scores of ABO‐identical versus ‐nonidentical recipients were 29 versus 34 for type O, 29 versus 19 for type A, 25 versus 38 for type B, and 22 versus 28 for type AB (p < 0.01). ABO‐nonidentical LT increased liver supply for candidates with blood types B and AB but decreased supply for type O and A candidates. We urge refinement of UNOS policy surrounding ABO‐nonidentical LT.     

Transplant trends in Mexico during the COVID-19 pandemic: Disparities within healthcare sectors

Healthcare systems worldwide were challenged during the COVID-19 pandemic. In Mexico, the public hospitals that perform most transplants were adapted to provide care for COVID-19 patients. Using a nationwide database, we describe the first report of the impact of COVID-19 and related transplantation healthcare policies in a middle-income country by comparing statistics before and during the pandemic (pre-COVID: March 2019–February 2020 vs. COVID era: March 2020–February 2021) and by type of institution (public vs. private). The global reduction in transplantation was higher in public institutions compared with private institutions, 89% versus 62%, respectively, p < .001. When analyzing by organ, kidney transplantation decreased by 89% at public versus 57% at private, p < .001; cornea by 88% at public versus 64% at private, p < .001; liver by 88% at public versus 35% at private, p < .001; and heart by 88% in public versus 67% at private institutions, p = .4. The COVID-19 pandemic along with the implemented health policies were associated with a decrease in donations, waiting list additions, and a decrease in transplantation, particularly at public institutions, which care for the most vulnerable.     

COVID-19 in pediatric kidney transplantation: The Improving Renal Outcomes Collaborative

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes.     

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.     

Transplant center experience influences spontaneous survival and waitlist mortality in acute liver failure: An analysis of the UNOS database

Transplant centers coordinate complex care in acute liver failure (ALF), for which liver transplant (LT) can be lifesaving. We studied associations between waitlist outcomes and center (1) ALF waitlist volume (low: <20; medium: 20-39; high: 40+ listings) and (2) total LT volume (<600, 600-1199, 1200+ LTs) in a retrospective cohort of 3248 adults with ALF listed for LT at 92 centers nationally from 2002 to 2019. Predicted outcome probabilities (LT, died/too sick, spontaneous survival [SS]) were obtained with multinomial regression, and observed-to-expected ratios were calculated. Median center outcome rates were 72.6% LT, 18.2% died/too sick, and 6.1% SS. SS was significantly higher with greater center ALF volume (median 0% for low-, 5.9% for medium-, and 8.6% for high-volume centers; P = .039), while waitlist mortality was highest at low-volume centers (median 21.4%, IQR: 16.1%-26.7%; P = .042). Significant heterogeneity in center performance was observed for waitlist mortality (observed-to-expected ratio range: 0-4.1) and particularly for SS (0-6.4), which persisted despite accounting for recipient case mix. This novel study demonstrates that increased center experience is associated with greater SS and reduced waitlist mortality for ALF. More-focused management pathways are needed to improve ALF outcomes at less-experienced centers and to identify opportunities for improvement at large.     

COVID-19 outcomes in patients waitlisted for kidney transplantation and kidney transplant recipients

The COVID-19 pandemic has brought unprecedented challenges to the transplant community. The reduction in transplantation volume during this time is partly due to concerns over potentially increased susceptibility and worsened outcomes of COVID-19 in immunosuppressed recipients. The consequences of COVID-19 on patients waitlisted for kidney transplantation, however, have not previously been characterized. We studied 56 waitlisted patients and 80 kidney transplant recipients diagnosed with COVID-19 between March 13 and May 20, 2020. Despite similar demographics and burden of comorbidities between waitlisted and transplant patients, waitlisted patients were more likely to require hospitalization (82% vs. 65%, P = .03) and were at a higher risk of mortality (34% vs. 16%, P = .02). Intubation was required in one third of hospitalized patients in each group, and portended a very poor prognosis. The vast majority of patients who died were male (84% waitlist, 100% transplant). Multivariate analysis demonstrated waitlist status, age, and male sex were independently associated with mortality. COVID-19 has had a dramatic impact on waitlisted patients, decreasing their opportunities for transplantation and posing significant mortality risk. Understanding the impact of COVID-19 on waitlist patients in comparison to transplant recipients may aid centers in weighing the risks and benefits of transplantation in the setting of ongoing COVID-19.     

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.     

Temporal trends in utilization and outcomes of steatotic donor livers in the United States

Steatotic donor livers (SDLs) (macrosteatosis ≥30%) represent a possible donor pool expansion, but are frequently discarded due to a historical association with mortality and graft loss. However, changes in recipient/donor demographics, allocation policy, and clinical protocols might have altered utilization and outcomes of SDLs. We used Scientific Registry of Transplant Recipients data from 2005 to 2017 and adjusted multilevel regression to quantify temporal trends in discard rates (logistic) and posttransplant outcomes (Cox) of SDLs, accounting for Organ Procurement Organization–level variation. Of 4346 recovered SDLs, 58.0% were discarded in 2005, versus only 43.1% in 2017 (P < .001). SDLs were always substantially more likely discarded versus non‐SDLs, although this difference decreased over time (adjusted odds ratio in 2005‐2007:_13.1515.28_17.74; 2008‐2011:_11.7713.41_15.29; 2012‐2014:_9.8711.37_13.10; 2015‐2017:_7.798.89_10.15, P < .001 for all). Conversely, posttransplant outcomes of recipients of SDLs improved over time: recipients of SDLs from 2012 to 2017 had 46% lower risk of mortality (adjusted hazard ratio [aHR]: _0.430.54_0.68, P < .001) and 47% lower risk of graft loss (aHR: _0.420.53_0.67, P < .001) compared to 2005 to 2011. In fact, in 2012 to 2017, recipients of SDLs had equivalent mortality (aHR: _0.901.04_1.21, P = .6) and graft loss (aHR: _0.901.04_1.20, P = .6) to recipients of non‐SDLs. Increasing utilization of SDLs might be a reasonable strategy to expand the donor pool.     

Nonstandard Exception Requests Impact Outcomes for Pediatric Liver Transplant Candidates

Nonstandard exceptions requests (NSERs), in which transplant centers appeal on a case‐by‐case basis for Pediatric End‐Stage Liver Disease/Mayo End‐Stage Liver Disease points, have been highly utilized for pediatric liver transplant candidates. We evaluated whether NSE outcomes are associated with waitlist and posttransplant mortality. United Network for Organ Sharing (UNOS) Scientific Registry of Transplant Recipients data on pediatric liver transplant candidates listed in 2009–2014 were analyzed after excluding those granted automatic UNOS exceptions. Of 2581 pediatric waitlist candidates, 44% had an NSE request. Of the 1134 children with NSERs, 93% were approved and 7% were denied. For children 2–18 years at listing, NSER denial increased the risk of waitlist mortality or removal for being too sick (subhazard ratio 2.99, 95% confidence interval [CI] 1.26–7.07, p = 0.01 in multivariate analysis). For children younger than 2 years, NSER denial did not impact waitlist mortality/removal. Children with NSER approved had reduced risk of graft loss 3 years posttransplant in univariate but not multivariable analysis (odds ratio 0.73, 95% CI 0.53–1.01, p = 06). Those with NSER denial had a higher risk of posttransplant death than those with no NSER (hazard ratio 2.43, 95% CI 0.99–5.95, p = 0.05, multivariable analysis), but NSER approval did not impact posttransplant death. Further research on NSER utilization in pediatric liver transplant is needed to optimize organ allocation and outcomes for children.     

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.