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.

Racial and ethnic differences and the role of unfavorable social determinants of health across steatotic liver disease subtypes in the United States.

BACKGROUND: The global liver community established a more precise criteria to characterize steatotic liver disease (SLD), specifically metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated and alcohol-associated liver disease (MetALD). We aimed to estimate the burden of SLD subtypes and unfavorable social determinants of health (SDOH) in US adults and whether clinical and social factors drive disparities across racial/ethnic subgroups. METHODS: We evaluated 4263 persons aged 20 years or older from the National Health and Nutrition Examination Survey 2017-2018. We estimated the weighted age-adjusted prevalence and severity of SLD, examined the prevalence of SDOH across SLD subtypes, and performed stepwise regression analysis to evaluate associations between race/ethnicity and SLD, accounting for metabolic risks, alcohol use, and SDOH. RESULTS: Hispanic adults had the highest prevalence of MASLD (22.3%), MASLD-predominant MetALD (10.3%), alcohol-associated liver disease (ALD)-predominant MetALD (5.6%), and ALD (5.4%). Hispanic adults with MASLD had the highest prevalence of high-risk metabolic dysfunction-associated steatohepatitis (18.0%) and advanced fibrosis (21.1%), whereas non-Hispanic (NH) White adults with MetALD had the highest prevalence of high-risk metabolic dysfunction-associated steatohepatitis (19.3%), advanced fibrosis (19.5%), and cirrhosis (8.1%). Adults with ALD-predominant MetALD and ALD had an increased burden of unfavorable SDOH than those with MASLD, particularly food insecurity, limited health care access, and single living. In stepwise regression, the odds of SLD in Hispanic adults decreased after adjusting for metabolic risks (OR 1.40, 95% CI, 1.06-1.84) and alcohol use (OR 1.36, 95% CI, 1.01-1.82). Differences did not persist after adjusting for cumulative SDOH and nativity status (OR 1.22, 95% CI, 0.89-1.68). CONCLUSIONS: We found substantial disparities in the burden of unfavorable SDOH across SLD subtypes, particularly among those with ALD-predominant MetALD and ALD. Population-based approaches targeting SDOH may mitigate racial/ethnic differences among US adults with SLD.

Enhanced Identification of Hispanic Ethnicity Using Clinical Data: A Study in the Largest Integrated United States Health Care System.

BACKGROUND: Collection of accurate Hispanic ethnicity data is critical to evaluate disparities in health and health care. However, this information is often inconsistently recorded in electronic health record (EHR) data. OBJECTIVE: To enhance capture of Hispanic ethnicity in the Veterans Affairs EHR and compare relative disparities in health and health care. METHODS: We first developed an algorithm based on surname and country of birth. We then determined sensitivity and specificity using self-reported ethnicity from the 2012 Veterans Aging Cohort Study survey as the reference standard and compared this to the research triangle institute race variable from the Medicare administrative data. Finally, we compared demographic characteristics and age-adjusted and sex-adjusted prevalence of conditions in Hispanic patients among different identification methods in the Veterans Affairs EHR 2018-2019. RESULTS: Our algorithm yielded higher sensitivity than either EHR-recorded ethnicity or the research triangle institute race variable. In 2018-2019, Hispanic patients identified by the algorithm were more likely to be older, had a race other than White, and foreign born. The prevalence of conditions was similar between EHR and algorithm ethnicity. Hispanic patients had higher prevalence of diabetes, gastric cancer, chronic liver disease, hepatocellular carcinoma, and human immunodeficiency virus than non-Hispanic White patients. Our approach evidenced significant differences in burden of disease among Hispanic subgroups by nativity status and country of birth. CONCLUSIONS: We developed and validated an algorithm to supplement Hispanic ethnicity information using clinical data in the largest integrated US health care system. Our approach enabled clearer understanding of demographic characteristics and burden of disease in the Hispanic Veteran population.

Waitlist and posttransplantation outcomes of lean individuals with nonalcoholic fatty liver disease.

Lean individuals with nonalcoholic fatty liver disease (NAFLD) represent a subset of patients with a distinct risk factor profile. We assessed the association between body mass index (BMI) on waitlist and postliver transplantation (LT) outcomes among these patients. We retrospectively analyzed the United Network for Organ Sharing data, including adult patients with NAFLD listed for LT between February 27, 2002, and June 30, 2020. We first used competing risk analyses to estimate the association of BMI with waitlist removal due to death or clinical deterioration. We then conducted Kaplan-Meier estimates and Cox regression models to determine the impact of weight change during the waiting list on all-cause mortality and graft failure after LT. Patients with normal weight (BMI 18.5-24.9 kg/m 2 ) suffered higher waitlist removal (adjusted subdistribution hazard ratio 1.26, 95% confidence interval [CI] 1.10-1.43; p = 0.001) compared with patients with obesity class I (BMI 30-34.9 kg/m 2 ). Those who remained at normal weight had higher all-cause mortality (adjusted hazard ratio [aHR] 1.61, 95% CI 1.32-1.96; p <0.001) and graft failure (aHR 1.57, 95% CI 1.32-1.88; p <0.001) than patients with stable obesity. Among patients with normal weight, those with the greatest weight increase (BMI gain ≥3 kg/m 2 ) had lower all-cause mortality (aHR 0.55, 95% CI 0.33-0.93; p = 0.03) and graft failure (aHR 0.49, 95% CI 0.30-0.81; p = 0.01) compared with patients with stable weight (BMI change ≤1 kg/m 2 ). Patients with NAFLD with normal weight have increased waitlist removal and those who remained at normal weight during the waitlist period have worse posttransplantation outcomes. Identifying and addressing factors influencing apparent healthy weight prior to LT are crucial to mitigate poor outcomes.

Comparison of transient elastography and Model for End-Stage Liver Disease-sodium to Model for End-Stage Liver Disease-sodium alone to predict mortality and liver transplantation.

OBJECTIVES: Model for End-Stage Liver Disease (MELD) alone and with sodium (MELD-Na) have decreasing predictive capacity as trends in liver disease evolve. We sought to combine transient elastography (TE) with MELD-Na to improve its predictive ability. METHODS: This is a retrospective cohort study comparing the use of TE, MELD-Na, and composite MELD-Na-TE to predict liver transplantation and all-cause mortality, with hepatic decompensation as a secondary outcome. Cox proportional hazards regression was used to measure predictive ability and control for confounders. RESULTS: Of the 214 patients, the mean age was 53 years with 35% being female and 76% being Caucasian. Hepatitis C (59%) and nonalcoholic fatty liver disease (22%) were the most frequent liver disease etiologies. On univariable analysis, MELD-Na [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06-1.2, P < 0.001], TE (HR 1.04, 95% CI 1.03-1.06, P < 0.001) and composite MELD-Na-TE (HR 1.13, 95% CI 1.08-1.19, P < 0.001) were associated with death or transplant. On multivariable analysis, MELD-Na was no longer significant (HR 1.08, 95% CI 0.95-1.22, P = 0.27) after adjusting for TE (HR 1.05, 95% CI 1.03-1.07, P < 0.001) while composite MELD-Na-TE remained significant (HR 1.16, 95% CI 1.09-1.24, P < 0.001). Composite MELD-Na-TE predicts mortality or liver transplant with the highest C-statistic of 0.81. Age (HR 1.05, 95% CI 1-1.09, P = 0.04), TE (HR 1.04, 95% CI 1.03-1.06, P < 0.001) and composite MELD-Na-TE (HR 1.11, 95% CI 1.06-1.15, P < 0.001) were significantly associated with hepatic decompensation. CONCLUSION: Composite MELD-Na-TE better predicts liver transplantation, death, and hepatic decompensation compared to MELD/MELD-Na or TE alone.

Maltodextrin-induced intestinal injury in a neonatal mouse model.

Prematurity and enteral feedings are major risk factors for intestinal injury leading to necrotizing enterocolitis (NEC). An immature digestive system can lead to maldigestion of macronutrients and increased vulnerability to intestinal injury. The aim of this study was to test in neonatal mice the effect of maltodextrin, a complex carbohydrate, on the risk of intestinal injury. The goal was to develop a robust and highly reproducible murine model of intestinal injury that allows insight into the pathogenesis and therapeutic interventions of nutrient-driven intestinal injury. Five- to 6-day-old C57BL/6 mice were assigned to the following groups: dam fed (D); D+hypoxia+Klebsiella pneumoniae; maltodextrin-dominant human infant formula (M) only; M+hypoxia; and M+hypoxia+K. pneumoniae. The mice in all M groups were gavage fed five times a day for 4 days. Mice were exposed to hypoxia twice a day for 10 min prior to the first and last feedings, and K. pneumoniae was added to feedings as per group assignment. Mice in all M groups demonstrated reduced body weight, increased small intestinal dilatation and increased intestinal injury scores. Maltodextrin-dominant infant formula with hypoxia led to intestinal injury in neonatal mice accompanied by loss of villi, increased MUC2 production, altered expression of tight junction proteins, enhanced intestinal permeability, increased cell death and higher levels of intestinal inflammatory mediators. This robust and highly reproducible model allows for further interrogation of the effects of nutrients on pathogenic factors leading to intestinal injury and NEC in preterm infants.This article has an associated First Person interview with the first author of the paper.

Long-term outcomes after liver transplantation in the Hispanic population.

BACKGROUND & AIMS: Racial/ethnic disparities in liver transplantation (LT) are well-recognized. Although Hispanics represent the largest and youngest minority group in the United States, limited data exist on long-term outcomes. We aimed to investigate long-term post-liver transplant outcomes in Hispanic patients and identify potential disparities compared to a baseline demographic of non-Hispanic white patients. METHODS: We performed a retrospective cohort study of first-time liver transplant recipients using the United Network for Organ Sharing database from 2002 to 2013, with follow-up through 2018. The primary outcomes of interest were overall patient and graft survival after LT. RESULTS: 45 767 patients underwent LT (85.0% non-Hispanic white, 15.0% Hispanic). Hispanics had lower socioeconomic status, higher prevalence of pretransplant comorbidities and more severe liver disease compared to non-Hispanic whites. Hispanics had similar patient (76.6% vs 75.6%; P = .12) and graft (71.7% vs 70.8%; P = .28) survival at 5 years and significantly better patient (62.9% vs 59.7%; P < .001) and graft (58.6% vs 55.6%; P = .002) survival at 10 years. In multivariable analysis, Hispanics had lower associated all-cause mortality (HR 0.86, 95% CI, 0.82-0.91; P < .001) and graft failure (HR 0.89, 95% CI, 0.85-0.93; P < .001) compared to non-Hispanic whites. In etiology-specific subanalysis, Hispanics transplanted for ALD, NASH and HCV had lower all-cause mortality compared to non-Hispanic whites. CONCLUSIONS: Hispanics have similar or better long-term post-LT outcomes compared to non-Hispanic whites despite a worse pretransplant risk factor profile. Further research is needed to clarify if this survival advantage reflects uncaptured protective factors or more stringent transplant selection in the Hispanic population.

Effect of polyunsaturated fatty acids on postnatal ileum development using the fat-1 transgenic mouse model.

BACKGROUND: Long-chain polyunsaturated fatty acids (LCPUFAs) play a critical role in neonatal health. We hypothesized that LCPUFAs play an essential role in priming postnatal gut development. We studied the effect of LCPUFAs on postnatal gut development using fat-1 transgenic mice, which are capable of converting n-6 to n-3 LCPUFAs, and wild-type (WT) C57BL/6 mice. METHODS: Distal ileum sections were collected from fat-1 and WT mice on days 3, 14, and 28. Fatty acid analyses, histology, RT-qPCR and intestinal permeability were performed. RESULTS: Fat-1 mice, relative to WT mice, showed increased n-3 LCPUFAs levels (α-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid, p < 0.05) and decreased arachidonic acid levels (p < 0.05) in the ileum. Preweaning fat-1 mice, compared to WT, showed >50% reduced muc2, Tff3, TLR9, and Camp expression (p < 0.05), markers of the innate immune response. There was a >two-fold increased expression of Fzd5 and EphB2, markers of cell differentiation (p < 0.05), and Fabp2 and 6, regulators of fatty acid transport and metabolism (p < 0.05). Despite reduced expression of tight junction genes, intestinal permeability in fat-1 was comparable to WT mice. CONCLUSIONS: Our data support the hypothesis that fatty acid profiles early in development modulate intestinal gene expression in formative domains, such as cell differentiation, tight junctions, other innate host defenses, and lipid metabolism.

Comparación de la efectividad de la dosis única frente a la dosis triple de cefazolina como profilaxis antibiótica en cesáreas / Comparison of single versus triple dose of cefazolin in antibiotic prophylaxis for caesarean section

Determinar la efectividad de la dosis única comparada con la dosis triple de Cefazolina como profilaxis antibiótica para reducir las infecciones post-cesárea. Material y Métodos: Estudio observacional, analítico, retrospectivo, transversal y comparativo. Se incluyó 82 historias clínicas de pacientes sometidas a cesárea en el Hospital Nacional Guillermo Almenara Irigoyen que recibieron dosis única o dosis triple de Cefazolina en el año 2011. De acuerdo al esquema recibido, se evaluaron las complicaciones infecciosas. Resultados: No hubo diferencia estadísticamente significativa entre la dosis única y la dosis triple en la incidencia de infecciones totales (9,3% vs 16,4%, p= 0,422), infección del sitio operatorio (7% vs 12,8%, p= 0,793), endometritis (0% vs 2,6%, p= 1,116) e infección del tracto urinario (2,3% vs 0%, p= 0,918). Conclusión: La dosis única de Cefazolina como profilaxis antibiótica fue igual de efectiva como la dosis triple en la prevención de la morbilidad infecciosa post-cesárea...

To compare the effectiveness of single dose versus triple dose of Cefazolinas prophylactic antibiotics in women undergoing cesarean section. Material and Methods: An observational, analytic, retrospective, cross sectional comparative study. Eighty two medical records of women undergoing caesarean section who received either single dose or triple dose in the Almenara Irigoyen Hospital were included. Women were compared on the basis of development of postoperative infections. Results: The study groups did not have statistically significant differences in the incidence of total infections (9,3% vs 16,4%, p= 0,422), wound infections(7% vs 12,8%, p= 0,793), endometritis (0% vs 2,6%, p= 1,116) and urinary tract infection(2,3% vs 0%, p= 0,918). Conclusion: A single prophylaxis dose of Cefazolin was as effective as triple dose in preventing post-caesarean infectious morbidity...