The role of an integrated referral program for patients with liver disease: A network between hub and spoke centers.

INTRODUCTION: Access to Liver transplantation (LT) can be affected by several barriers, resulting in delayed referral and increased risk of mortality due to complications of the underlying liver disease. AIM: To assess the clinical characteristics and outcomes of patients with acute or chronic liver disease referred using an integrated referral program. MATERIALS AND METHODS: An integrated referral program was developed in 1 October 2017 based on email addresses and a 24/7 telephone availability. All consecutive adult patients with liver disease referred for the first time using this referral program were prospectively collected until 1 October 2021. Characteristics and outcomes of inpatients were compared with a historical cohort of patients referred without using the integrated referral program (1 October 2015-1 October 2017). Patients were further divided according to pre- and post-Covid-19 pandemic. RESULTS: Two hundred eighty-one referred patients were considered. End stage liver disease was the most common underlying condition (79.3%), 50.5% of patients were referred as inpatients and 74.7% were referred for LT evaluation. When inpatient referrals (n = 142) were compared with the historical cohort (n = 86), a significant increase in acute liver injury due to drugs/herbals and supplements was seen (p = 0.01) as well as an increase in End stage liver disease due to alcohol-related liver disease and NASH, although not statistically significant. A significant increase in referrals for evaluation for Trans-jugular intrahepatic portosystemic shunt placement was seen over time (5.6% vs. 1%; p = 0.01) as well as for LT evaluation (84.5% vs. 81%; p = 0.01). Transplant-free survival was similar between the study and control groups (p = 0.3). The Covid-19 pandemic did not affect trends of referrals and patient survival. CONCLUSIONS: The development of an integrated referral program for patients with liver disease can represent the first step to standardize already existing referral networks between hub and spoke centers. Future studies should focus on the timing of referral according to different etiologies to optimize treatment options and outcomes.

Factors Associated With Liver Transplant Referral Among Patients With Cirrhosis at Multiple Safety-Net Hospitals.

Importance: A high proportion of underserved patients with cirrhosis receive care at safety-net hospitals (SNHs). While liver transplant (LT) can be a life-saving treatment for cirrhosis, data on referral patterns from SNHs to LT centers are lacking. Objective: To identify factors associated with LT referral within the SNH context. Design, Setting, and Participants: This retrospective cohort study included 521 adult patients with cirrhosis and model for end-stage liver disease-sodium (MELD-Na) scores of 15 or greater. Participants received outpatient hepatology care at 3 SNHs between January 1, 2016, and December 31, 2017, with end of follow-up on May 1, 2022. Exposures: Patient demographic characteristics, socioeconomic status, and liver disease factors. Main Outcomes and Measures: Primary outcome was referral for LT. Descriptive statistics were used to describe patient characteristics. Multivariable logistic regression was performed to evaluate factors associated with LT referral. Multiple chained imputation was used to address missing values. Results: Of 521 patients, 365 (70.1%) were men, the median age was 60 (IQR, 52-66) years, most (311 [59.7%]) were Hispanic or Latinx, 338 (64.9%) had Medicaid insurance, and 427 (82.0%) had a history of alcohol use (127 [24.4%] current vs 300 [57.6%] prior). The most common liver disease etiology was alcohol associated liver disease (280 [53.7%]), followed by hepatitis C virus infection (141 [27.1%]). Median MELD-Na score was 19 (IQR, 16-22). One hundred forty-five patients (27.8%) were referred for LT. Of these, 51 (35.2%) were wait-listed, and 28 (19.3%) underwent LT. In a multivariable model, male sex (adjusted odds ratio [AOR], 0.50 [95% CI, 0.31-0.81]), Black race vs Hispanic or Latinx ethnicity (AOR, 0.19 [95% CI, 0.04-0.89]), uninsured status (AOR, 0.40 [95% CI, 0.18-0.89]), and hospital site (AOR, 0.40 [95% CI, 0.18-0.87]) were associated with lower odds of being referred. Reasons for not being referred (n = 376) included active alcohol use and/or limited sobriety (123 [32.7%]), insurance issues (80 [21.3%]), lack of social support (15 [4.0%]), undocumented status (7 [1.9%]), and unstable housing (6 [1.6%]). Conclusions: In this cohort study of SNHs, less than one-third of patients with cirrhosis and MELD-Na scores of 15 or greater were referred for LT. The identified sociodemographic factors negatively associated with LT referral highlight potential intervention targets and opportunities to standardize LT referral practices to increase access to life-saving transplant among underserved patients.

Identifying and understanding variation in population-based access to liver transplantation in the United States.

We aimed to identify variations in liver transplant access across transplant referral regions (TRRs), accounting for differences in population characteristics and practice environments. Adult end-stage liver disease (ESLD) deaths and liver waitlist additions from 2015 to 2019 were included. The primary outcome was listing-to-death ratio (LDR). We modeled the LDR as a continuous variable and obtained adjusted LDR estimates for each TRR, accounting for clinical and demographic characteristics of ESLD decedents, socioeconomic and health care environment within the TRR, and characteristics of the transplant environment. The overall mean LDR was 0.24 (range: 0.10-0.53). In the final model, proportion of patients living in poverty and concentrated poverty was negatively associated with LDR; organ donation rate was positively associated with LDR. The R2 was 0.60, indicating that 60% of the variability in LDR was explained by the model. Approximately 40% of this variation remained unexplained and may be due to transplant center behaviors amenable to intervention to improve access to care for patients with ESLD.

Association Between End-Stage Liver Disease and Incident Heart Failure in an Integrated Health System.

BACKGROUND: End-stage liver disease (ESLD) and heart failure (HF) often coexist and are associated with significant morbidity and mortality. However, the true incidence of HF among patients with ESLD remains understudied. OBJECTIVE: This study aims to evaluate the association between ESLD and incident HF in a real-world clinical cohort. DESIGN AND PARTICIPANTS: A retrospective electronic health records database analysis of individuals with ESLD and frequency-matched controls without ESLD in a large integrated health system. MAIN MEASURES: The primary outcome was incident HF, which was defined by the International Classification of Disease codes and manually adjudicated by physician reviewers. The Kaplan-Meier method was used to estimate the cumulative incidence of HF. Multivariate proportional hazards models adjusted for shared metabolic factors (diabetes, hypertension, chronic kidney disease, coronary heart disease, body mass index) were used to compare the risk of HF in patients with and without ESLD. KEY RESULTS: Of 5004 patients (2502 with ESLD and 2502 without ESLD), the median (Q1-Q3) age was 57.0 (55.0-65.0) years, 59% were male, and 18% had diabetes. Over a median (Q1-Q3) follow-up of 2.3 (0.6-6.0) years, 121 incident HF cases occurred. Risk for incident HF was significantly higher for patients with ESLD compared with the non-ESLD group (adjusted HR: 4.67; 95% CI: 2.82-7.75; p < 0.001), with the majority of the ESLD group (70.7%) having HF with preserved ejection fraction (ejection fraction ≥ 50%). CONCLUSION: ESLD was significantly associated with a higher risk of incident HF, independent of shared metabolic risk factors, with the predominant phenotype being HF with preserved ejection fraction.

Does COVID-19 infection significantly affect liver transplantation? Results of liver transplantation in the COVID-19 era at a single, high-volume centre.

BACKGROUND: Liver transplantation is a proven management method for end-stage cirrhosis and is estimated to have increased life expectancy by 15 years. The COVID-19 pandemic posed a challenge to patients who were candid for a solid-organ transplant. It has been suggested that the outcomes of liver transplants could be adversely affected by the infection, as immunosuppression makes liver transplant candidates more susceptible to adverse effects while predisposing them to higher thrombotic events. MATERIAL AND METHODS: In this retrospective study, the cases who received liver transplants from January 2018 to March 2022 were assessed regarding early postoperative mortality rate and hepatic artery thrombosis (HAT) with COVID-19 infection. This study included 614 cases, of which 48 patients were infected. RESULTS: This study shows that the early COVID-19-related early postoperative mortality rates substantially increased in the elective setting (OR: 2.697), but the results for the acute liver failure were insignificant. The average model for end-stage liver disease score increased significantly during the pandemic due to new regulations. Although mortality rates increased during the pandemic, the data for the vaccination period show that mortality rates have equalised with the prepandemic era. Meanwhile, COVID-19 infection is assumed to have increased HAT by 1.6 times in the elective setting. CONCLUSION: This study shows that COVID-19 infection in an acute liver failure poses comparatively little risk; hence transplantation should be considered in such cases. Meanwhile, the hypercoagulative state induced by the infection predisposes this group of patients to higher HAT rates.

National frequency, trends, and healthcare burden of care fragmentation in readmissions for end-stage liver disease in the USA.

BACKGROUND: End-stage liver disease (ESLD) patients have frequent readmissions to the same facility or a different hospital (care fragmentation). Care fragmentation results in care delivery from an unfamiliar clinical team or setting, a potential source of suboptimal clinical outcomes. We examined the occurrence, trends, and association between care fragmentation and outcomes during readmissions for ESLD. METHODS: From the Nationwide Readmissions Database (January to September 2010-2014), we followed adult (age ≥18 years) hospitalizations for ESLD who were discharged alive for 90 days. During 30- and 90-day readmissions, we calculated the frequency, determinants, and clinical outcomes of care fragmentation (SAS 9.4). RESULTS: Of the 67,480 ESLD hospitalizations surviving at discharge from 2010-2014, 35% (23,872) and 52% (35,549) were readmitted in 30- and 90-days respectively. During readmissions, the frequencies of care fragmentation were similar (30-day: 25.4% and 90-day: 25.8%) and remained stable from 2010 to 2014 (P trends>0.5). Similarly, factors associated with care fragmentation were consistent across 30- and 90-day readmissions. These included ages: 18-44 years, liver cancer, receipt of liver transplantation, hepatorenal syndrome, prolonged length of stay, and hospitalization in non-teaching facilities. During 30- and 90-day readmissions, care fragmentation was associated with higher risk of mortality (adjusted mean ratio: 1.13[1.03-1.24] and 1.14 [1.06-1.23]; P values<0.0001), prolonged length of stay (4.6-days vs. 4.1-days and 5.2-days vs. 4.6-days; P values<0.0001), and higher hospital charges ($36,884 vs. $28,932 and $37,354 vs. $30,851; P values<0.0001). CONCLUSIONS: Care fragmentation is high among readmissions for ESLD and is associated with poorer outcomes.

Preoperative Coronary Intervention Before Orthotopic Liver Transplantation (from a Review of Literature).

There is significant morbidity and mortality associated with the presence of coronary artery disease (CAD) in the setting of orthotopic liver transplantation in patients with end-stage liver disease. The prevalence of CAD in this cohort is similar to, if not higher, than the general population. Several studies show improved survival rates for patients with obstructive CAD who undergo percutaneous coronary intervention (PCI) and support a low threshold for PCI in these patients. However, a few studies have failed to show improved mortality associated with PCI in this cohort. This review hopes to highlight the current recommendations regarding the assessment of CAD in patients with end-stage liver disease who are orthotopic liver transplantation candidates and describe the outcomes of PCIs.

Changing trends in aetiology-based hospitalizations with end-stage liver disease in the United States from 2016 to 2019.

BACKGROUNDS AND AIMS: A potent and safe antiviral agent may impact chronic hepatitis C (HCV)-related end-stage liver disease (ESLD). We assess aetiology-based hospitalizations for ESLD in the United States, 2016-2019. METHODS: We utilized the National Inpatient Sample (NIS) from 2016 to 2019. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma, criteria obtained from the International Classification of Diseases, Tenth Revision. RESULTS: National hospitalization rates for non-alcoholic fatty liver disease (NAFLD) increased significantly from 67.1/100 000 persons in 2016 to 93.6 in 2019 with an average annual percentage change (AAPC) of 12.1%, while chronic hepatitis C (HCV) decreased significantly from 71.2/100 000 persons in 2016 to 58.5 in 2019 (-6.5% AAPC). Hospitalizations for ESLD in alcohol-related liver disease (ALD) increased as well. CONCLUSIONS: Hospitalization rates for NAFLD- and ALD-related ESLD increased steadily, while those for HCV-related ESLD decreased during the direct-acting antivirals era.

Do contemporary antiretrovirals increase the risk of end-stage liver disease? Signals from patients starting therapy in the North American AIDS Cohort Collaboration on Research and Design.

PURPOSE: Despite effective antiretroviral therapy, rates of end-stage liver disease (ESLD) remain high. It is not clear whether contemporary antiretrovirals contribute to the risk of ESLD. METHODS: We included patients from cohorts with validated ESLD data in the North American AIDS Cohort Collaboration on Research and Design. Patients had to initiate antiretroviral therapy after 1 January 2004 with a nucleos(t)ide backbone of either abacavir/lamivudine or tenofovir/emtricitabine and a contemporary third (anchor) drug. Patients were followed until a first ESLD event, death, end of a cohort's ESLD validation period, loss to follow-up or 31 December 2015. We estimated associations between cumulative exposure to each drug and ESLD using a hierarchical Bayesian survival model with weakly informative prior distributions. RESULTS: Among 10 564 patients included from 12 cohorts, 62 had an ESLD event. Of the nine anchor drugs, boosted protease inhibitors atazanavir and darunavir had the strongest signals for ESLD, with increasing hazard ratios (HR) and narrowing credible intervals (CrI), from a prior HR of 1.5 (95% CrI 0.32-7.1) per 5 year's exposure to posterior HRs respectively of 1.8 (95% CrI 0.82-3.9) and 2.0 (95% CrI 0.86-4.7). Both backbones and efavirenz showed no signal. Hepatitis C coinfection was the most important covariate risk factor (HR 4.4, 95% CrI 2.6-7.0). CONCLUSIONS: While contemporary antiretrovirals pose less risk for ESLD than hepatitis coinfection, atazanavir and darunavir had a toxicity signal. We show how hierarchical Bayesian modelling can be used to detect toxicity signals in cohort event monitoring data even with complex treatments and few events.

Best Practices in Large Database Clinical Epidemiology Research in Hepatology: Barriers and Opportunities.

With advances in computing and information technology, large health care research databases are becoming increasingly accessible to investigators across the world. These rich, population-level data sources can serve many purposes, such as to generate "real-world evidence," to enhance disease phenotyping, or to identify unmet clinical needs, among others. This is of particular relevance to the study of patients with end-stage liver disease (ESLD), a socioeconomically and clinically heterogeneous population that is frequently under-represented in clinical trials. This review describes the recommended "best practices" in the execution, reporting, and interpretation of large database clinical epidemiology research in hepatology. The advantages and limitations of selected data sources are reviewed, as well as important concepts on data linkages. The appropriate classification of exposures and outcomes is addressed, and the strategies needed to overcome limitations of the data and minimize bias are explained as they pertain to patients with ESLD and/or liver transplantation (LT) recipients. Lastly, selected statistical concepts are reviewed, from model building to analytic decision making and hypothesis testing. The purpose of this review is to provide the practical insights and knowledge needed to ensure successful and impactful research using large clinical databases in the modern era and advance the study of ESLD and LT.

Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

BACKGROUND & AIMS: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy. METHODS: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p <0.001) and a higher probability of being transplanted (HR 2.27; 95% CI 1.78-2.90; p = 0.001) in ERA-2 compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio 0.56; 95% CI 0.46-0.68; p = 0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high-volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high-volume center and ERA-2, while MELD ≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD ≥30 priority allocation was associated with improved patient outcomes, although MELD ≥30 was associated with a higher risk of graft loss. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes.

Sex Disparity in Liver Transplant and Access to Living Donation.

Importance: The Model for End-stage Liver Disease (MELD)-based organ allocation system has significantly decreased mortality on the transplant waiting list for patients with end-stage liver disease. However, women have remained at a disadvantage with respect to access to deceased donor liver transplant (DDLT) even after introduction of the MELD score for organ allocation. Objective: To determine whether availability of living donation in a transplant program can offset inequity in liver transplant (LT) allocation for women. Design, Setting, and Participants: This cohort study retrospectively analyzed adult patients listed for LT at the University Health Network in Toronto, Ontario, Canada. Patients included had a potential living donor (pLD) at the moment of listing. This study was performed from November 13, 2012, to May 31, 2019. A total of 1289 listed patients (830 men; 459 women) were analyzed during the study period. Main Outcomes and Measures: This study performed survival analysis and competing-risk analysis to delineate how access to livers from living donors was associated with events in women vs men on the transplant waiting list (LT, death, or dropout). Results: Of 1289 included patients, 459 (35.6%) were women, and the mean (SD) age was 56.1 (10.0) years at assessment and listing. A total of 783 of 1289 listed patients underwent LT. Among those with no pLD at assessment, there was a higher median (range) Model for End-stage Liver Disease incorporating sodium levels (MELD-Na) score at listing (22 [6-50] vs 19 [6-50]; P < .001) and at LT (27 [6-49] vs 20 [6-52]; P < .001) in women receiving DDLT. Women were at a significant disadvantage without a pLD (hazard ratio [HR], 1.29; 95% CI, 1.04-1.60; P = .01); there was no difference in access to LT with availability of a pLD (HR, 0.93; 95% CI, 0.76,-1.14; P = .44). The instantaneous rate of receiving a transplant in men with a pLD was 1.39 times higher than men who did not have a pLD (HR, 1.39; 95% CI; P < .001) and the instantaneous rate of receiving a transplant in women with a pLD was 1.92 times higher than in women who did not (HR, 1.92; 95% CI, 1.51-2.44; P < .001). The HR was 1.38 times higher in women compared with men across the MELD-Na score strata (HR, 1.38; 95% CI, 1.03-1.84; P = .03) and 2.04 times higher when the MELD-Na score was less than 20 (HR, 2.04; 95% CI, 1.31-3.14; P = .001). Conclusions and Relevance: These study findings suggest that women can overcome the complex problem of allocation inequity with access to livers from living donors. Women with access only to DDLT were much more unwell than men independent of liver disease at the time of listing, dropout, or LT. Therefore, the wider availability of living donation liver transplant would be helpful in addressing the sex disparity in access to LT in the current MELD-Na era.

Prognostic value of hepatorenal function following transcatheter edge-to-edge mitral valve repair.

BACKGROUND: Hepatorenal dysfunction is a strong prognostic predictor in patients with heart failure. However, the prognostic impact of the hepatorenal dysfunction in patients undergoing transcatheter mitral valve repair (TMVR) has not been well studied. METHODS: In consecutive patients who underwent edge-to-edge TMVR at three German centers, the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score was calculated as 5.11 × ln [serum total bilirubin (mg/dl)] + 11.76 × ln [serum creatinine (mg/dl)] + 9.44. Patients were stratified into high (> 11) or low (≤ 11) MELD-XI score of which an incidence of the composite outcome, consisting of all-cause mortality and heart failure hospitalization, within 2 years after TMVR was assessed. RESULTS: Of the 881 patients, the mean MELD-XI score was 11.0 ± 5.9, and 415 patients (47.1%) had high MELD-XI score. The MELD-XI score was correlated with male, effective regurgitant orifice area, and tricuspid regurgitation severity and inversely related to left ventricular ejection fraction. Patients with high MELD-XI score had a higher incidence of the composite outcome than those with low MELD-XI score (47.7% vs. 29.8%; p < 0.0001), and in multivariable analysis, the high MELD-XI score was an independent predictor of the composite outcome [adjusted hazard ratio (HR) 1.34; 95% confidence interval (CI) 1.02-1.77; p = 0.04). Additionally, the MELD-XI score as a continuous variable was also an independent predictor (adjusted HR 1.02; 95% CI 1.00-1.05; p = 0.048). CONCLUSIONS: The MELD-XI score was associated with clinical outcomes within 2 years after TMVR and can be a useful risk-stratification tool in patients undergoing TMVR.

Drug-induced liver injury in Australia, 2009-2020: the increasing proportion of non-paracetamol cases linked with herbal and dietary supplements.

OBJECTIVE: To compare the characteristics and outcomes of drug-induced liver injury (DILI) caused by paracetamol and non-paracetamol medications, particularly herbal and dietary supplements. DESIGN: Retrospective electronic medical record data analysis. SETTING, PARTICIPANTS: Adults admitted with DILI to the Gastroenterology and Liver Centre at the Royal Prince Alfred Hospital, Sydney (a quaternary referral liver transplantation centre), 2009-2020. MAIN OUTCOME MEASURES: 90-day transplant-free survival; drugs implicated as causal agents in DILI. RESULTS: A total of 115 patients with paracetamol-related DILI and 69 with non-paracetamol DILI were admitted to our centre. The most frequently implicated non-paracetamol medications were antibiotics (19, 28%), herbal and dietary supplements (15, 22%), anti-tuberculosis medications (six, 9%), and anti-cancer medications (five, 7%). The number of non-paracetamol DILI admissions was similar across the study period, but the proportion linked with herbal and dietary supplements increased from 2 of 13 (15%) during 2009-11 to 9 of 19 (47%) during 2018-20 (linear trend: P = 0.011). Despite higher median baseline model for end-stage liver disease (MELD) scores, 90-day transplant-free survival for patients with paracetamol-related DILI was higher than for patients with non-paracetamol DILI (86%; 95% CI, 79-93% v 71%; 95% CI, 60-82%) and herbal and dietary supplement-related cases (59%; 95% CI, 34-85%). MELD score was an independent predictor of poorer 90-day transplant-free survival in both paracetamol-related (per point increase: adjusted hazard ratio [aHR], 1.19; 95% CI, 1.09-3.74) and non-paracetamol DILI (aHR, 1.24; 95% CI, 1.14-1.36). CONCLUSION: In our single centre study, the proportion of cases of people hospitalised with DILI linked with herbal and dietary supplements has increased since 2009. Ninety-day transplant-free survival for patients with non-paracetamol DILI, especially those with supplement-related DILI, is poorer than for those with paracetamol-related DILI.

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.

Long Term Follow-up of Liver Transplant Recipients: Considerations for Non-transplant Specialists.

Patient and liver graft survival rates have improved significantly in the last decades, leading to complications mainly related to long-term immunosuppression. Prevention of, screening for metabolic syndrome, cardiovascular disease, de novo diabetes mellitus, renal dysfunction, and malignancies and their management are mandatory due to important causes of morbidity and mortality in this patient population. Quality of life (QoL) and functional benefits are clearly better compared to preoperative status; however, post-liver transplantation (LT) complications may impair and alter QoL scores. Individualized immunosuppression managed by transplant physicians and collaboration with other non-transplant specialists for recognition and treatment of medical complications and comorbidities after LT is the key to enhanced QoL and life expectancy of this patient population.

Coronavirus Disease 2019 and Liver Transplantation: Lessons from the First Year of the Pandemic.

Over the last year, the novel coronavirus disease 2019 (COVID-19) has continued to spread across the globe, causing significant morbidity and mortality among transplantation candidates and recipients. Patients with end-stage liver disease awaiting liver transplantation and patients with a history of liver transplantation represent vulnerable populations, especially given the high rates of associated medical comorbidities in these groups and their immunosuppressed status. In addition, concerns surrounding COVID-19 risk in this patient population have affected rates of transplantation and general transplantation practices. Here, we explore what we have learned about the impact of COVID-19 on liver transplantation candidates and recipients as well as the many key knowledge gaps that remain.

Prevalence of COVID-19 in patients with autoimmune liver disease in Europe: A patient-oriented online survey.

BACKGROUND: During the current SARS-CoV-2 pandemic it is important to identify risk factors for COVID-19. Registry studies are providing growing evidence on the elevated risk of mortality from COVID-19 in patients with chronic liver disease, especially in advanced stages. Results may, however, have a selection bias towards severe cases. Limited data is available on COVID-19 in patients with autoimmune liver disease (AILD). AIM: To perform an online survey to capture the prevalence of COVID-19 and the state of medical care of patients with AILD in Europe during the pandemic. METHODS: Data was collected via an anonymous patient-oriented, online survey, which was available on the EUSurvey platform in nine European languages between 24th June 2020 and 14th October 2020. Of 1834 contributions, 51 were excluded because participants did not name an underlying AILD, and four were excluded because of duplicate data entry. RESULTS: Of 1,779 participants, 1,752 resided in 20 different countries of the European Union and the United Kingdom (UK). The five countries with the highest numbers of contributions were France (n = 450), Germany (n = 318), the Netherlands (n = 267), Spain (n = 225), and the UK (n = 183). 2.2% of participants (39/1779) had been diagnosed with COVID-19. There were no differences regarding age, sex, AILD, the status of liver cirrhosis, or status post liver transplantation between COVID-19 and non-COVID-19 cases. Of the 39 COVID-19 cases, five patients were admitted to a regular ward, one patient was admitted to ICU and required ventilation. CONCLUSION: In our Europe-wide, patient-oriented survey on COVID-19 in patients with AILD, we detected a low rate of COVID-19, comparable to the period prevalence of the general population. These results suggest that patients with AILD are not at elevated risk of COVID-19.

Changing demographics and risk factors for cryptococcosis: A 12-year review at a tertiary care centre.

BACKGROUND: Cryptococcosis is classically associated with the immunocompromised patients but there is a rising appreciation for its impact on the immunocompetent hosts. We sought to analyse the trends, diagnosis, treatment of different hosts and the effect of immunodeficiency and chronic liver disease on relapse and in-house mortality. METHODS: This is a retrospective study of 12 years of patients with cryptococcosis, divided into three different groups: HIV-infected, transplant and non-HIV non-transplant (NHNT). Data were analysed with Chi-square, unpaired parametric t test, simple and multivariate logistic regression analysis. RESULTS: Of 114 identified patients, 23 (20.2%) had HIV infection, 11 (9.6%) had transplant, 80 (70.2%) were NHNT patients. Overall, mortality was 28.1% (32/114) and relapse occurred in 10.5% (12/114) of patients. The mortality trend was higher (OR = 2.346, p = .287) in the transplant group (45.5%, 5/11) than in HIV (26.1%, 6/23) and NHNT groups (26.3%, 21/80). HIV was associated with relapse; 30.4% (7/23) for HIV-positive patients and 5.5% (5/91) for HIV-negative patients (OR = 7.525, p = .002). Chronic liver disease had a large and statistically significant association with mortality on multivariate analysis (OR = 3.583, p = .013) which was more pronounced than the HIV or transplant groups. It was independently associated with mortality by chi-square analysis (OR 3.137, p = .012). CONCLUSION: Chronic liver disease represented 30.7% (35/114) of all studied patients. It was a risk factor for in-hospital mortality. HIV infection and transplant were not statistically significant for mortality. Relapse was highest in the HIV-infected patients at 30.4% (7/23). These data highlight the effect of type and degree of immunocompromise on cryptococcosis.