The Association Between the Origin of the Donation After Circulatory Death Liver Recovery Team and Graft Survival: A National Study.

Background: Transplant centers have traditionally relied upon procurement teams from their own programs (transplant program procurement team [TPT]) to recover donation after circulatory death (DCD) livers and rarely use surgical procurement teams not affiliated with the recipient center (nontransplant program procurement team [NTPT]). However, in the era of wider geographic organ sharing, greater reliance on NTPTs is often necessary. Methods: We used national data to study the association between the origin of the donor procurement team (NTPT versus TPT) and the risk of DCD liver allograft failure. Results: Five hundred NTPT and 2257 TPT DCD transplants were identified: 1-y graft survival was 88.9 and 88.6%, respectively (P = 0.962). In a multivariable model, the origin of the procurement team was not associated with graft failure NTPT versus TPT (hazard ratio, 0.92; 95% confidence interval, 0.71-1.22; P = 0.57) but rather with known risks for DCD graft loss including donor age, degree of recipient illness, cold ischemic time, and retransplantation. The overall incidence of retransplantation and ischemic cholangiopathy as an indication for retransplantation were similar between NTPT and TPT. Conclusions: This data suggests that transplant centers may be able to safely use DCD livers recovered by local surgical teams.

Rabies control in Bangladesh and prediction of human rabies cases by 2030: a One Health approach.

Background: Bangladesh is making progress toward achieving zero dog-mediated rabies deaths by 2030, a global goal set in 2015. Methods: Drawing from multiple datasets, including patient immunisation record books and mass dog vaccination (MDV) databases, we conducted a comprehensive analysis between 2011 and 2023 to understand the effectiveness of rabies control programmes and predict human rabies cases in Bangladesh by 2030 using time-series forecasting models. We also compared rabies virus sequences from GenBank in Bangladesh and other South Asian countries. Findings: The estimated dog population in Bangladesh was determined to be 1,668,140, with an average dog population density of 12.83 dogs/km2 (95% CI 11.14-14.53) and a human-to-dog ratio of 86.70 (95% CI 76.60-96.80). The MDV campaign has led to the vaccination of an average of 21,295 dogs (95% CI 18,654-23,935) per district annually out of an estimated 26,065 dogs (95% CI 22,898-29,230). A declining trend in predicted and observed human rabies cases has been identified, suggesting that Bangladesh is poised to make substantial progress towards achieving the 'Zero by 30' goal, provided the current trajectory continues. The phylogenetic analysis shows that rabies viruses in Bangladesh belong to the Arctic-like-1 group, which differs from those in Bhutan despite sharing a common ancestor. Interpretation: Bangladesh's One Health approach demonstrated that an increase in MDV and anti-rabies vaccine (ARV) resulted in a decline in the relative risk of human rabies cases, indicating that eliminating dog-mediated human rabies could be achievable. Funding: The study was supported by the Communicable Disease Control (CDC) Division of the Directorate General of Health Services (DGHS) of the People's Republic of Bangladesh.

Clinical Course of Bio Naive Ulcerative Colitis Patients Five Years After Initiation of Adalimumab in a Nationwide Cohort.

Background: There is limited data on the long-term clinical outcomes of bio-naïve ulcerative colitis (UC) patients who are initiated on adalimumab (ADA). Our study aims to evaluate the clinical course of a nationwide cohort of bio naïve UC patients who were started on ADA, and then followed for 5 years after initiation of the drug. Methods: We conducted a retrospective cohort study using the US Veteran Affairs Healthcare System (VAHS). Bio naïve UC patients were followed for 5 years after initiation of ADA. The primary outcome was to determine the time to discontinuation of ADA and if patients achieved endoscopic remission by the end of follow-up. Results: A total of 387 patients were included among whom 193 (49.87%) had pancolitis. The highest rate of ADA discontinuation was within the first year, with the elderly having a higher rate of discontinuation (HR 1.67, 95% CI: 1.14-2.45) and those on concomitant immunomodulators having a lower rate of discontinuation (HR 0.70, 95% CI: 0.48-1.03). In total, 125 (32.30%) patients remained on ADA at the end of their maximum follow-up. 54 (43.90%) achieved endoscopic remission. Conclusion: Among bio-naive UC patients who were started on ADA, a third were still on the drug at the end of 5 years and half had endoscopic remission. The rate of discontinuation was highest within the first year of initiation, but patients continued to stop the drug over the course of follow-up.

The Association Between Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Exposure and Key Cirrhosis-Related Outcomes.

INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) may have hepatic benefits in patients with primarily chronic liver disease. ACE-I/ARB have not been evaluated in broad cohorts inclusive of those with decompensated cirrhosis. We analyzed the real-world association between ACE-I/ARB exposure and cirrhosis-related outcomes in a national cohort. METHODS: We performed a retrospective, active comparator new user study of patients with cirrhosis in the Veterans Health Administration. We identified new initiators of ACE-I/ARB or calcium channel blockers (comparator). Inverse probability treatment weighting balanced key confounders and Cox regression evaluated the association between ACE-I/ARB and outcomes of mortality, cirrhosis decompensation, and hepatocellular carcinoma (HCC). In exploratory analysis, cause-specific competing risk models evaluated liver-related vs cardiovascular (CV)-related vs nonliver/non-CV-related mortality. RESULTS: There were 904 ACE-I/ARB and 352 calcium channel blocker new initiators. In inverse probability treatment weighting Cox regression, ACE-I/ARB exposure was associated with reduced mortality (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.61-0.81, P < 0.001). In patients with compensated cirrhosis, ACE-I/ARB were not associated with hepatic decompensation or HCC. Cause-specific hazard models showed ACE-I/ARB exposure was associated with reduction in nonliver/non-CV-related mortality (cause-specific HR 0.49, 95% CI 0.38-0.62, P < 0.001) but not liver-related or CV-related mortality. In Child-Turcotte-Pugh A patients, ACE-I/ARB were associated with decreased CV-related mortality (cause-specific HR 0.41, 95% CI 0.26-0.65, P < 0.001). DISCUSSION: ACE-I/ARB exposure was associated with reduced mortality, potentially through CV and other (renal, malignancy-related) mechanisms. In patients with compensated disease, ACE-I/ARB were not associated with hepatic decompensation or HCC. Future research should identify subsets of patients who benefit from ACE-I/ARB exposure.

Preoperative Hepatology and Primary Care Visits Improve Postoperative Outcomes in Patients with Cirrhosis Undergoing Surgery.

BACKGROUND AND AIMS: Cirrhosis patients are at increased risk for postoperative complications. It remains unclear whether preoperative nonsurgical clinician visits improve postoperative outcomes. We assessed the impact of preoperative primary care physician (PCP) and/or gastroenterologist/hepatologist (GI/Hep) visits on postoperative mortality in cirrhosis patients undergoing surgery and explored differences in medication changes and paracentesis rates as potential mediators. METHODS: This was a retrospective cohort study of cirrhosis patients in the Veterans Health Administration who underwent surgery between 2008 and 2016. We compared 1982 patients with preoperative PCP and/or GI/Hep visits with 1846 propensity-matched patients without preoperative visits. We used Cox regression and Fine and Gray competing risk regression to evaluate the association between preoperative visit type and postoperative mortality at 6 months. RESULTS: Patients with preoperative GI/Hep and PCP visits had a 45% lower hazard of postoperative mortality compared with those without preoperative visits (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.35-0.87). A smaller effect size was noted with GI/Hep preoperative visit alone (HR, 0.69; 95% CI, 0.48-0.99) or PCP visit alone (HR, 0.70; 95% CI, 0.53-0.93). Patients with preoperative PCP/GI/Hep visits were more likely to have diuretics, spontaneous bacterial peritonitis prophylaxis, and hepatic encephalopathy medications newly initiated and/or dose adjusted and more likely to receive preoperative paracentesis as compared with those without preoperative visits. CONCLUSIONS: Preoperative PCP/GI/Hep visits are associated with a reduced risk of postoperative mortality with the greatest risk reduction observed in those with both PCP and GI/Hep visits. This synergistic effect highlights the importance of a multidisciplinary approach in the preoperative care of cirrhosis patients.

Performance of race-neutral eGFR equations in patients with decompensated cirrhosis.

The 2021 Chronic Kidney Disease Epidemiology Collaboration equation [CKD-EPI 2021] is a race-neutral equation recently developed and rapidly implemented as a reference standard to estimate glomerular filtration rate(GFR). However, its role in cirrhosis has not been examined especially in low GFR. We analyzed the performance of CKD-EPI 2021 compared to other equations with protocol-measured GFR (mGFR) in cirrhosis. We analyzed 2090 unique adult patients with cirrhosis undergoing protocol GFR measurements using iothalamate clearance from 1985 to 2015 when listed for liver transplantation at Baylor University in Dallas and Fort Worth, Texas. Using mGFR as a reference standard, the CKD-EPI 2021 was compared to CKD-EPI 2012, Modification of Diet in Renal Disease-4, Modification of Diet in Renal Disease-6, Royal Free Hospital, and GFR Assessment in Liver disease overall and in certain subgroups (ascites, mGFR ≤ 30 mL/min/1.73 m 2 , diagnosis, Model for End-Stage Liver Disease and gender). We examined bias (difference between eGFR and mGFR), accuracy (p30: eGFR within ± 30% of mGFR) and agreement between eGFR and mGFR categories. CKD-EPI 2021 had the second lowest bias across the entire range of GFR after GFR Assessment in Liver disease (6.6 vs. 4.6 mL/min/1.73 m 2 , respectively, p < 0.001). The accuracy of CKD-EPI 2021 was similar to CKD-EPI 2012 (p30 = 67.8% vs. 67.9%, respectively) which was higher than the other equations ( p < 0.001). It had a similar performance in patients with ascites, by diagnoses, Model for End-Stage Liver Disease subgroups, by gender, and in non-Black patients. However, it had a relatively higher overestimation in mGFR ≤ 30 mL/min/1.73 m 2 than most equations (18.5 mL/min/1.73m 2 , p < 0.001). Specifically, 64% of patients with mGFR ≤ 30 mL/min/1.73m 2 were incorrectly classified as a less severe CKD stage by CKD-EPI 2021. In Blacks, CKD-EPI 2021 underestimated eGFR by 17.9 mL/min/1.73 m 2 , which was higher than the alternate equations except for Royal Free Hospital ( p < 0.001). The novel race-neutral eGFR equation, CKD-EPI 2021, improves the GFR estimation overall but may not accurately capture true kidney function in cirrhosis, specifically at low GFR. There is an urgent need for a race-neutral equation in liver disease reflecting the complexity of kidney function physiology unique to cirrhosis, given implications for organ allocation and dual organ transplant.

National Trends in Utilization of Normothermic Machine Perfusion in DCD Liver Transplantation.

Background: In liver transplantation, advances in ex situ normothermic machine perfusion (NMP) have improved outcomes compared with traditional static cold storage (SCS) in donation after circulatory death (DCD) organs. We aimed to characterize trends in the utilization of NMP versus SCS in DCD liver transplantation in the United States. Methods: This retrospective cohort study used data from the United Network for Organ Sharing database to identify recipient-donor adult liver transplant pairs from DCD donors from January 2016 to June 2022. Utilization of NMP and changes in donor risk index (DRI) and components between NMP and SCS were assessed across transplant year eras (2016-2018, 2019-2020, and 2021-2022). Statistical comparisons were made using the Kruskal-Wallis test or the chi-square test. Results: A total of 3937 SCS and 127 NMP DCD donor transplants were included. Utilization of NMP ranged from ~0.4% to 3.5% from 2016 to 2021 and rose significantly to 11.2% in early 2022. Across transplant eras, median DRI increased significantly for SCS and NMP, but the magnitude of the increase was larger for NMP. With NMP DCDs, there were significant increases in median donor age, national share proportion, and "cold ischemic time" over time. Finally, there was a shift toward including higher DRI donors and higher model for end-stage liver disease score transplant recipients with NMP in later transplant eras. Conclusions: In recent years, NMP utilization has increased and expanded to donors with higher DRI and recipients with higher model for end-stage liver disease score at transplant, suggesting increasing familiarity and risk tolerance with NMP technology. As NMP remains a relatively new technique, ongoing study of patient outcomes, organ allocation practices, and utilization patterns is critical.

Waitlisting and liver transplantation for MetALD in the United States: An analysis of the UNOS national registry.

BACKGROUND AND AIMS: The new steatotic liver disease (SLD) nomenclature introduced metabolic and alcohol-associated liver disease (MetALD), describing the intersection of metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease. Waitlisting and liver transplantation for MetALD are not well defined. We aimed to develop and validate an algorithm for identifying SLD phenotypes and assessing trends in waitlisting and transplant outcomes. APPROACH AND RESULTS: We conducted a retrospective cohort study using the United Network for Organ Sharing registry, supplemented with detailed single-center data. We developed 5 candidate algorithms for SLD classification and calculated their diagnostic performance. Trends in waitlist registrations and transplants were estimated, and competing risk analyses and Cox regression models were conducted to assess waitlist removal and posttransplant outcomes among SLD phenotypes. The best-performing algorithm demonstrated substantial agreement (weighted kappa, 0.62) for SLD phenotypes, with acceptable sensitivity (73%) for MetALD. Between 2002 and 2022, waitlist registrations and transplants for MetALD increased 2.9-fold and 3.3-fold, respectively. Since 2013, there has been a significant increase in the absolute number of waitlist registrations (122 per year; 95% CI, 111-133) and transplants (107 per year; 95% CI, 94-120) for MetALD. Patients with MetALD experienced higher waitlist removal (adjusted subdistribution hazard ratio, 1.10; 95% CI, 1.03-1.17), all-cause mortality (adjusted hazard ratio, 1.13; 95% CI, 1.03-1.23), and graft failure (adjusted hazard ratio, 1.12; 95% CI, 1.03-1.21) than those with alcohol-associated liver disease. CONCLUSIONS: We developed and validated an algorithm for identifying SLD phenotypes in UNOS. MetALD is the third leading etiology among those waitlisted and underwent transplantation, exhibiting worse pretransplantation and posttransplantation outcomes compared to alcohol-associated liver disease. Identifying and addressing factors determining poor outcomes is crucial in this patient population.