Impact of COVID-19 Pandemic on Liver Transplantation and Alcohol-Associated Liver Disease in the USA.

BACKGROUND AND AIMS: The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD. APPROACH AND RESULTS: Using data from United Network for Organ Sharing, we analyzed wait-list outcomes in the USA through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019, and February 29, 2020, were defined as the "pre-COVID" era, and after April 1, 2020, were defined as the "COVID" era. Interrupted time-series analyses using monthly count data from 2016-2020 were constructed to evaluate the rate change for listing and LT before and during the COVID-19 pandemic. Rates for listings (P = 0.19) and LT (P = 0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P < 0.001) and NASH (-13.18%; P < 0.001). There was a significant increase in ALD listing (+7.26%; P < 0.001) and LT (10.67%; P < 0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcohol-associated hepatitis (+50%). Patients with ALD presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a Model for End-Stage Liver Disease-Sodium score ≥30. CONCLUSIONS: Since the start of COVID-19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on health care resources.

Impact of the COVID-19 pandemic on liver donation and transplantation: A review of the literature.

The coronavirus disease 2019 (COVID-19) pandemic has upended healthcare systems worldwide and led to an inevitable decrease in liver transplantation (LT) activity. During the first pandemic wave, administrators and clinicians were obliged to make the difficult decision of whether to suspend or continue a life-saving procedure based on the scarce available evidence regarding the risk of transmission and mortality in immunosuppressed patients. Those centers where the activity continued or was heavily restricted were obliged to screen donors and recipients, design COVID-safe clinical pathways, and promote telehealth to prevent nosocomial transmission. Despite the ever-growing literature on COVID-19, the amount of high-quality literature on LT remains limited. This review will provide an updated view of the impact of the pandemic on LT programs worldwide. Donor and recipient screening, strategies for waitlist prioritization, and posttransplant risk of infection and mortality are discussed. Moreover, a particular focus is given to the possibility of donor-to-recipient transmission and immunosuppression management in COVID-positive recipients.

Characteristics, Trends, and Outcomes of Liver Transplantation for Primary Sclerosing Cholangitis in Female Versus Male Patients: An Analysis From the European Liver Transplant Registry.

BACKGROUND: The influence of sex on primary sclerosing cholangitis (PSC), pre- and postliver transplantation (LT) is unclear. Aims are to assess whether there have been changes in incidence, profile, and outcome in LT-PSC patients in Europe with specific emphasis on sex. METHODS: Analysis of the European Liver Transplant Registry database (PSC patients registered before 2018), including baseline demographics, donor, biochemical, and clinical data at LT, immunosuppression, and outcome. RESULTS: European Liver Transplant Registry analysis (n = 6463, 32% female individuals) demonstrated an increasing number by cohort (1980-1989, n = 159; 1990-1999, n = 1282; 2000-2009, n = 2316; 2010-2017, n = 2549) representing on average 4% of all transplant indications. This increase was more pronounced in women (from 1.8% in the first cohort to 4.3% in the last cohort). Graft survival rate at 1, 5, 10, 15, 20, and 30 y was 83.6%, 70.8%, 57.7%, 44.9%, 30.8%, and 11.6%, respectively. Variables independently associated with worse survival were male sex, donor and recipient age, cholangiocarcinoma at LT, nondonation after brain death donor, and reduced size of the graft. These findings were confirmed using a more recent LT population closer to the current standard of care (LT after the y 2000). CONCLUSIONS: An increasing number of PSC patients, particularly women, are being transplanted in European countries with better graft outcomes in female recipients. Other variables impacting outcome include donor and recipient age, cholangiocarcinoma, nondonation after brain death donor, and reduced graft size.

Using Geographic Catchment Areas to Measure Population-based Access to Kidney Transplant in the United States.

BACKGROUND: Monitoring efforts to improve access to transplantation requires a definition of the population attributable to a transplant center. Previously, assessment of variation in transplant care has focused on differences between administrative units-such as states-rather than units derived from observed care patterns. We defined catchment areas (transplant referral regions [TRRs]) from transplant center care patterns for population-based assessment of transplant access. METHODS: We used US adult transplant listings (2006-2016) and Dartmouth Atlas catchment areas to assess the optimal method of defining TRRs. We used US Renal Data System and Scientific Registry of Transplant Recipient data to compare waitlist- and population-based kidney transplant rates. RESULTS: We identified 110 kidney, 67 liver, 85 pancreas, 68 heart, and 43 lung TRRs. Most patients were listed in their assigned TRR (kidney: 76%; liver: 75%; pancreas: 75%; heart: 74%; lung: 72%), although the proportion varied by organ (interquartile range for kidney, 65.7%-82.5%; liver, 58.2%-78.8%; pancreas, 58.4%-81.1%; heart, 63.1%-80.9%; lung, 61.6%-76.3%). Patterns of population- and waitlist-based kidney transplant rates differed, most notably in the Northeast and Midwest. CONCLUSIONS: Patterns of TRR-based kidney transplant rates differ from waitlist-based rates, indicating that current metrics may not reflect transplant access in the broader population. TRRs define populations served by transplant centers and could enable future studies of how transplant centers can improve access for patients in their communities.

Early impact of COVID-19 on transplant center practices and policies in the United States.

COVID-19 is a novel, rapidly changing pandemic: consequently, evidence-based recommendations in solid organ transplantation (SOT) remain challenging and unclear. To understand the impact on transplant activity across the United States, and center-level variation in testing, clinical practice, and policies, we conducted a national survey between March 24, 2020 and March 31, 2020 and linked responses to the COVID-19 incidence map. Response rate was a very high 79.3%, reflecting a strong national priority to better understand COVID-19. Complete suspension of live donor kidney transplantation was reported by 71.8% and live donor liver by 67.7%. While complete suspension of deceased donor transplantation was less frequent, some restrictions to deceased donor kidney transplantation were reported by 84.0% and deceased donor liver by 73.3%; more stringent restrictions were associated with higher regional incidence of COVID-19. Shortage of COVID-19 tests was reported by 42.5%. Respondents reported a total of 148 COVID-19 recipients from <1 to >10 years posttransplant: 69.6% were kidney recipients, and 25.0% were critically ill. Hydroxychloroquine (HCQ) was used by 78.1% of respondents; azithromycin by 46.9%; tocilizumab by 31.3%, and remdesivir by 25.0%. There is wide heterogeneity in center-level response across the United States; ongoing national data collection, expert discussion, and clinical studies are critical to informing evidence-based practices.

Current status of liver transplantation in Latin America.

The lack of adequate financial coverage, education, and the organization has been the main limiting factor for the development of transplantation in Latin America. As occurred worldwide, the number of patients on liver waiting lists in Latin America grows disproportionately compared to the number of liver transplantations (LTs) performed. Although many law modifications have been made in the last year, most countries lack social awareness about the importance of donation and the irreversibility of brain death. The mechanisms and norms for organ procurement and infrastructure development, capable of supporting this high demand, are still in slow progress in most countries. Access to LT in the region is very heterogeneous. While some countries have no active LT programs so far, others are an international model of a public transplantation system (Brazil) or a national information system (Argentina). While some countries have only a few LT centers, others have too many LT centers performing an inadequate low number of LTs. Disparity to access transplantation remains the major challenge in the region. Cultural and educational efforts have to be accompanied by transparent public policies that will likely increase organ donation and activity in transplantation. The purpose of this article is to review the trends and current activity in LT within Latin America, based on prior publications and the information available in each country of the region.

Temporal Changes and Regional Variation in Acceptance of Hepatitis C Virus-Viremic Livers.

The high efficacy of current hepatitis C virus (HCV) therapy and increased numbers of HCV-infected deceased donors have changed the paradigm of HCV in liver transplantation (LT). Modeling studies have been performed to evaluate the optimal timing of HCV treatment (before versus after LT) in HCV-infected patients and to assess the cost-effectiveness of transplanting HCV-infected livers into HCV- patients. However, these models rely on historical data and have not quantified the temporal changes in the median Model for End-Stage Liver Disease (MELD) score at transplant of recipients of an HCV-infected liver across geographic areas. We performed a retrospective cohort study of Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) data of nonstatus 1 deceased donor LT recipients from January 1, 2016, to December 31, 2018, and we calculated the difference in allocation MELD score in recipients of HCV nucleic acid test (NAT)- versus NAT+ livers by year and UNOS region. We used Pearson correlation coefficients to assess the relationship between MELD score difference in recipients of HCV NAT+ versus HCV NAT- livers and the proportion of non-HCV recipients of HCV NAT+ livers. Nationally, the allocation MELD score difference at LT in recipients of HCV NAT+ versus NAT- livers did not change (4-point difference). This stability was seen in regions 3, 5, and 10. In regions 1, 7, 8, 9, and 11, the MELD score difference decreased, which is a diminishing advantage. However, in regions 2 and 4, it increased, which is a rising advantage. In 2018, recipients of HCV NAT+ livers had a lower MELD score in 9/11 regions, and the MELD score advantage of accepting HCV NAT+ livers had a moderate inverse correlation with the regional use in non-HCV patients (r = -0.53). These data should be used to inform clinicians of the pre- and post-LT trade-offs of HCV treatment.

Predictors of low risk for dropout from the liver transplant waiting list for hepatocellular carcinoma in long wait time regions: Implications for organ allocation.

All patients with hepatocellular carcinoma meeting United Network for Organ Sharing T2 criteria currently receive the same listing priority for liver transplant (LT). A previous study from our center identified a subgroup with a very low risk of waitlist dropout who may not derive immediate LT benefit. To evaluate this issue at a national level, we analyzed within the United Network for Organ Sharing database 2052 patients with T2 hepatocellular carcinoma receiving priority listing from 2011 to 2014 in long wait time regions 1, 5, and 9. Probabilities of waitlist dropout were 18.3% at 1 year and 27% at 2 years. In multivariate analysis, factors associated with a lower risk of waitlist dropout included Model for End-Stage Liver Disease-Na < 15, Child's class A, single 2- to 3-cm lesion, and α-fetoprotein ≤20 ng/mL. The subgroup of 245 (11.9%) patients meeting these 4 criteria at LT listing had a 1-year probability of dropout of 5.5% vs 20% for all others (P < .001). On explant, the low dropout risk group was more likely to have complete tumor necrosis (35.5% vs 24.9%, P = .01) and less likely to exceed Milan criteria (9.9% vs 17.7%, P = .03). We identified a subgroup with a low risk of waitlist dropout who should not receive the same LT listing priority.

Assessment of Trends in Transplantation of Liver Grafts From Older Donors and Outcomes in Recipients of Liver Grafts From Older Donors, 2003-2016.

Importance: In light of the growing population of older adults in the United States, older donors (aged ≥70 years) represent an expansion of the donor pool; however, their organs are underused. Liver grafts from older donors were historically associated with poor outcomes and higher discard rates, but clinical protocols, organ allocation, and the donor pool have changed in the past 15 years. Objective: To evaluate trends in demographics, discard rates, and outcomes among older liver donors and transplant recipients of livers from older donors in a large national cohort. Design, Setting, and Participants: Prospective cohort study of 4127 liver grafts from older donors and 3350 liver-only recipients of older donor grafts and 78 990 liver grafts from younger donors (aged 18-69 years) and 64 907 liver-only recipients of younger donor grafts between January 1, 2003, and December 31, 2016, in the United States. The Scientific Registry of Transplant Recipients, which includes data on all transplant recipients in the United States that are submitted by members of the Organ Procurement and Transplantation Network, was used. Exposures: Year of liver transplant and age of liver donor. Main Outcomes and Measures: Odds of graft discard and posttransplant outcomes of all-cause graft loss and mortality. Results: In this study, 4127 liver grafts from older donors were recovered for liver transplant across the study period (2003-2016); 747 liver grafts from older donors were discarded, and 3350 liver grafts from older donors were used for liver-only recipients. After adjusting for donor characteristics other than age and accounting for Organ Procurement Organization-level variation, liver grafts from older donors were more likely to be discarded compared with liver grafts from younger donors in 2003-2006 (adjusted odds ratio [aOR], 1.97; 95% CI, 1.68-2.31), 2007-2009 (aOR, 2.55; 95% CI, 2.17-3.01), 2010-2013 (aOR, 2.04; 95% CI, 1.68-2.46), and 2013-2016 (aOR, 2.37; 95% CI, 1.96-2.86) (P < .001 for all). Transplants of liver grafts from older donors represented a progressively lower proportion of all adult liver transplants, from 6.0% (n = 258 recipients) in 2003 to 3.2% (n = 211 recipients) in 2016 (P = .001). However, outcomes in recipients of grafts from older donors improved over time, with 40% lower graft loss risk (adjusted hazard ratio, 0.60; 95% CI, 0.53-0.68; P < .001) and 41% lower mortality risk (adjusted hazard ratio, 0.59; 95% CI, 0.52-0.68; P < .001) in 2010 through 2016 vs 2003 through 2009; these results were beyond the general temporal improvements in graft loss (interaction P = .03) and mortality risk (interaction P = .04) among recipients of liver grafts from younger donors. Conclusions and Relevance: These findings show that from 2003 to 2016, liver graft loss and mortality among recipients of liver grafts from older donors improved; however, liver graft discard from older donors remained increased and the number of transplants performed with liver grafts from older donors decreased. Expansion of the donor pool through broader use of liver grafts from older donors might be reasonable.

Future Trends in Demand for Liver Transplant: Birth Cohort Effects Among Patients With NASH and HCC.

BACKGROUND: With increasing US adiposity, nonalcoholic steatohepatitis (NASH) is now a leading liver transplant (LT) indication. Given its association with hepatocellular carcinoma (HCC), the burden of NASH is substantial. We analyzed birth cohort effects among NASH LT registrants, with and without HCC. METHODS: All new LT registrants in United Network for Organ Sharing (1995-2015) were identified. Birth cohorts were defined as: 1936-1940, 1941-1945, 1946-1950, 1951-1955, 1956-1960, 1961-1965, 1966-1970, 1971-2015. Poisson regression examined trends in LT registration, by disease etiology (NASH, hepatitis C virus [HCV], other liver disease etiologies [OTHER]), and HCC. RESULTS: We identified 182 368 LT registrants with median age of 52 years (range, 0-86 years). Nine percent (n = 16 160) had NASH, 38% (n= 69 004) HCV, 53% (n = 97 204) OTHER. HCC was present in: 13% (n = 2181), 27% (n = 18 295), and 11% (n = 10 902), of NASH, HCV, and OTHER, respectively. Liver transplant registration for HCC increased significantly from 2002 to 2015 across all etiologies (NASH, 6%-18%; HCV, 19%-51%; OTHER, 9%-16%; P < 0.0001 for all). NASH LT registrations, with and without HCC, increased sharply in patients born from 1945 to 2015. This upward NASH trend is in stark contrast to HCV LT registrations, which showed a general decline. Notably, a sharp rise in LT registrations is occurring among younger NASH patients (35-55 years), mirroring the increasing adiposity across all age groups in the US population. CONCLUSIONS: NASH LT registrants, with and without HCC, have increased over time, and are projected to increase unabated in the future, notably among younger birth cohorts ("Adipose Wave Effect"). HCC LT registration patterns demonstrate that, compared with HCV, NASH patients encompass younger birth cohorts. These data illustrate that the full impact of NASH on demand for LT is yet to be realized.

Patient Satisfaction and Healthcare Utilization Using Telemedicine in Liver Transplant Recipients.

BACKGROUND: Post-liver transplantation care is limited to tertiary care centers. Concentration at expert centers leads to high-volume clinics with long wait times and decreased accessibility. AIM: To assess whether telemedicine can be utilized to overcome barriers to care while sustaining strong patient-physician relationships. METHODS: The Patient Satisfaction Questionnaire-18, Telemedicine Satisfaction Questionnaire, and Health Utilization Questionnaire were used to assess patient satisfaction and healthcare utilization among patients who received care via video connection (telemedicine group) and in clinic (control group). Propensity matching was performed. Scores for questionnaires were reported as mean and standard deviations (SD) and were compared by one-way multivariate analysis of variance and one-way analysis of variance. RESULTS: There were 21 matched telemedicine patients in our study. Overall mean age (± SD) was 51 (± 5.62) years and 52 (± 6.12) years for telemedicine group and control group, respectively. General patient satisfaction was similar between the two groups (p = 0.89). While telemedicine patients were just as satisfied with communication and interpersonal approach compared to clinic patients, they experienced significantly less commute (p < 0.0001) and waiting (p < 0.0001) times. Given ease of using telemedicine without compromising patient-physician interaction, 90% (19/21) of the telemedicine patients opted to use the service again. CONCLUSION: Telemedicine appeared to be both a time and cost-saving alternative to clinic follow-up without compromise of the valuable patient-physician relationship. Telemedicine has the potential to improve clinic flow, reduce wait times, and decrease costs for liver transplant recipients.

Current Status and Future Challenges of Liver Transplantation Programs in Chile.

Liver transplantation (LT) was performed for the first time in Chile in 1969, but only since the 1990s has it been systematically performed. Our health system is strongly centralized, which is a severe limitation for the patients who need to be evaluated and subsequently listed. Although proper human and technological resources are available and our results are comparable to international outcomes (overall patient survival at 1, 5, and 10 years of 82%, 70%, and 64%, respectively), we are limited because of a severe scarcity of grafts, which translates into an availability of approximately 7 organs per million persons and a wait-list dropout rate of 40% every year. Thus, our main challenge for the next few years is to improve access to LT among the populations from the extreme regions of the country and overall to improve the availability of grafts by increasing the awareness of physicians in intensive care units and emergency departments, to develop living donor LT programs, to educate the population in order to decrease family refusal, and to reinforce the system of potential donor detection. Although hard work is mandatory for these improvements, none of these tasks seem to be unreachable in the midterm.

Increasing Liver Transplantation Wait-List Dropout for Hepatocellular Carcinoma With Widening Geographical Disparities: Implications for Organ Allocation.

Given the increasing incidence of hepatocellular carcinoma (HCC) and regional variation in liver transplantation (LT) rates for HCC, we investigated temporal and geographic disparities in LT and wait-list dropout. LT candidates receiving Model for End-Stage Liver Disease (MELD) exception from 2005 to 2014 were identified from the United Network for Organ Sharing database (n = 14,320). Temporal differences were compared across 2 eras (2005-2009 and 2010-2014). Regional groups were defined based on median wait time as long-wait region (LWR; regions 1, 5, and 9), mid-wait region (MWR; regions 2, 4, 6, 7, and 8), and short-wait region (SWR; regions 3, 10, and 11). Fine and Gray competing risk regression estimated risk of wait-list dropout as hazard ratios (HRs). The cumulative probability of LT within 3 years was 70% in the LWR versus 81% in the MWR and 91% in the SWR (P < 0.001). From 2005-2009 to 2010-2014, median time to LT increased by 6.0 months (5.6 to 11.6 months) in the LWR compared with 3.8 months (2.6 to 6.4 months) in the MWR and 1.3 months (1.0 to 2.3 months) in the SWR. The cumulative probability of dropout within 3 years was 24% in the LWR versus 16% in the MWR and 8% in the SWR (P < 0.001). From 2005-2009 to 2010-2014, the LWR also had the greatest increase in probability of dropout. Risk of dropout was increased in the LWR (HR, 3.5; P < 0.001) and the MWR (HR, 2.2; P < 0.001) compared with the SWR, and year of MELD exception 2010-2014 (HR, 1.9; P < 0.001) compared with 2005-2009. From 2005-2009 to 2010-2014, intention-to-treat 3-year survival decreased from 69% to 63% in the LWR (P < 0.001), 72% to 69% in the MWR (P = 0.008), and remained at 74% in the SWR (P = 0.48). In conclusion, we observed a significant increase in wait-list dropout in HCC patients in recent years that disproportionately impacted LWR patients. Widening geographical disparities call for changes in allocation policy as well as enhanced efforts at increasing organ donation and utilization.

Status of Adult Living Donor Liver Transplantation in the United States: Results from the Adult-To-Adult Living Donor Liver Transplantation Cohort Study.

This article reviews the Adult-to-Adult Living Donor Liver Transplant Cohort Study (A2ALL). The findings show that the number of adult-to-adult living donor liver transplants is consistently increasing. Living donor liver transplantation has an important benefit for patients with acute liver failure, does not compromise donor safety, and has lower rates of acute cellular rejection in biologically related donor and recipient. The conclusions from the A2ALL consortium have been critical in transplant advancement, supporting increased use to help decrease waitlist death and improve long-term survival of transplant recipients.

Change in Health Insurance Coverage After Liver Transplantation Can Be Associated with Worse Outcomes.

BACKGROUND: Health insurance coverage changes for many patients after liver transplantation, but the implications of this change on long-term outcomes are unclear. AIMS: To assess post-transplant patient and graft survival according to change in insurance coverage within 1 year of transplantation. METHODS: We queried the United Network for Organ Sharing for patients between ages 18-64 years undergoing liver transplantation in 2002-2016. Patients surviving > 1 year were categorized by insurance coverage at transplantation and the 1-year transplant anniversary. Multivariable Cox regression characterized the association between coverage pattern and long-term patient or graft survival. RESULTS: Among 34,487 patients in the analysis, insurance coverage patterns included continuous private coverage (58%), continuous public coverage (29%), private to public transition (8%) and public to private transition (4%). In multivariable analysis of patient survival, continuous public insurance (HR 1.29, CI 1.22, 1.37, p < 0.001), private to public transition (HR 1.17, CI 1.07, 1.28, p < 0.001), and public to private transition (HR 1.14, CI 1.00, 1.29, p = 0.044), were associated with greater mortality hazard, compared to continuous private coverage. After disaggregating public coverage by source, mortality hazard was highest for patients transitioning from private insurance to Medicaid (HR vs. continuous private coverage = 1.32; 95% CI 1.14, 1.52; p < 0.001). Similar differences by insurance category were found for death-censored graft failure. CONCLUSION: Post-transplant transition to public insurance coverage is associated with higher risk of adverse outcomes when compared to retaining private coverage.