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Background: Considering the expected increase in the elderly population and the growing emphasis on aging-related biomedical research, the demand for aged laboratory animals has surged, challenging established husbandry practices. Our objective was to establish a cost-effective method for environmental enrichment, utilizing the liver as a representative organ to assess potential metabolic changes in response to differing enrichment levels. Methods: We conducted a six-month study involving 24 male Sprague Dawley rats, randomly assigned to four environmental enrichment groups. Two groups were housed in standard cages, while the others were placed in modified rabbit cages. Half of the groups received weekly playtime in an activity focused rat housing unit. We evaluated hormone levels, playtime behavior, and subjective handling experience. Additionally, liver tissue proteomic analysis was performed. Results: Initial corticosterone levels and those after 3 and 6 months showed no significant differences. Yet, testosterone levels were lower in the control group by the end of the study (p = 0.007). We observed 1871 distinct proteins in liver tissue, with 77% being common across groups. In gene ontology analysis, no specific pathways were overexpressed. In semiquantitative analysis, we observed differences in proteins associated in lipid metabolism such as Apolipoprotein A-I and Acyl-CoA 6-desaturase, which were lower in the control group (p = 0.024 and p = 0.009). Rats in the intervention groups with weekly playtime displayed the least amount of reported distress during inspection or upon room entry and were less prone to accepting treats. Removing animals from their enclosure was most effortless for those in the large cage group. Over time, there was a decrease in conflicts among rats that interacted only twice weekly during playpen time. Discussion: In summary, refining husbandry practices for aging rats is both simple and budget-friendly, with no apparent adverse effects on stress levels, animal development, or relevant metabolic changes in the liver. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV)‐infection and reactivation remain a relevant complication after liver transplantation (LT). The recipient and donor serum CMV‐IgG‐status has been established for risk stratification when choosing various pharmaceutical regimens for CMV‐prophylaxis in the last two decades. However, factors influencing course of CMV‐infection in LT remain largely unknown. In this study, the impact of immunosuppressive regimen was examined in a large cohort of patients. Methods: All patients that underwent primary LT between 2006 and 2018 at the Charité–Universitaetsmedizin, Berlin, were included. Clinical course as well as histological and laboratory findings of patients were analyzed our prospectively maintained database. Univariate and multivariate regression analysis for impact of variables on CMV‐occurrence was conducted, and survival was examined using Kaplan–Meier analysis. Results: Overall, 867 patients were included in the final analysis. CMV‐infection was diagnosed in 325 (37.5%) patients after transplantation. Significantly improved overall survival was observed in these patients (Log rank = 0.03). As shown by correlation and regression tree classification and regression tree analysis, the recipient/donor CMV‐IgG‐status with either positivity had the largest influence on CMV‐occurrence. Analysis of immunosuppressive burden did not reveal statistical impact on CMV‐infection, but statistically significant inverse correlation of cumulative tacrolimus trough levels and survival was found (Log rank <.001). Multivariate analysis confirmed these findings (p =.02). Discussion: CMV‐infection remains of clinical importance after LT. Undergone CMV‐infection of either recipient or donor requires prophylactic treatment. Additionally, we found a highly significant, dosage‐dependent impact of immunosuppression (IS) on long‐term outcomes for these patients, underlying the importance of minimization of IS in liver transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Pre‐transplant deceased donor liver biopsy may impact decision making; however, interpretation of the results remains variable and depends on accepting center practice patterns. Methods: In this cohort study, adult recipients from 04/01/2015–12/31/2020 were identified using the UNOS STARfile data. The deceased donor liver biopsies were stratified by risk based on degree of fibrosis, macrovesicular fat content, and level of portal infiltration (low‐risk: no fibrosis, no portal infiltrates, and <30% macrosteatosis; moderate‐risk: some fibrosis or mild infiltrates and <30% macrosteatosis; high‐risk: most fibrosis, moderate/marked infiltrates, or ≥30% macrosteatosis). Graft utilization, donor risk profile, and recipient outcomes were compared across groups. Results: Of the 51,094 donor livers available, 20,086 (39.3%) were biopsied, and 34,606 (67.7%) were transplanted. Of the transplanted livers, 14,908 (43.1%) were biopsied. The transplanted grafts had lower mean macrovesicular fat content (9.3% transplanted vs. 26.9% non‐transplanted, P < 0.001) and less often had any degree of fibrosis (20.9% vs. 39.9%, P < 0.001) or portal infiltration (51.3% vs. 58.2%, P < 0.001) versus non‐transplanted grafts. Post‐transplant recipient LOS (14.2 days high‐risk vs. 15.2 days low‐risk, P = 0.170) and 1‐year graft survival (90.5% vs. 91.7%, P = 0.137) did not differ significantly between high‐ versus low‐risk groups. Kaplan‐Meier survival estimates further revealed no differences in the 5‐year graft survival across risk strata (P = 0.833). Of the 5178 grafts biopsied and turned down, PSM revealed 1338 (26.0%) were potentially useable based on biopsy results and donor characteristics. Conclusion: Carefully matched deceased donor livers with some fibrosis, inflammation, or steatosis ≥30% may be suitable for transplantation. Further study of this group of grafts may decrease turndowns of potentially useable organs. [ABSTRACT FROM AUTHOR]

Background: Body composition alterations are frequent in patients with cancer or chronic liver disease, but their prognostic value remains unclear in many cancer entities. Objective: We investigated the impact of disease aetiology and body composition after surgery for intrahepatic cholangiocarcinoma (iCCA), a rare and understudied cancer entity in European and North American cohorts. Methods: Computer tomography‐based assessment of body composition at the level of the third lumbar vertebra was performed in 173 patients undergoing curative‐intent liver resection for iCCA at the Department of Surgery, Charité – Universitätsmedizin Berlin. Muscle mass and ‐composition as well as subcutaneous and visceral adipose tissue quantity were determined semi‐automatically. (Secondary) sarcopenia, sarcopenic obesity, myosteatosis, visceral and subcutaneous obesity were correlated to clinicopathological data. Results: Sarcopenia was associated with post‐operative morbidity (intraoperative transfusions [p = 0.027], Clavien–Dindo ≥ IIIb complications [p = 0.030], post‐operative comprehensive complication index, CCI [p < 0.001]). Inferior overall survival was noted in patients with myosteatosis (33 vs. 23 months, p = 0.020). Fifty‐eight patients (34%) had metabolic (dysfunction)‐associated fatty liver disease (MAFLD) and had a significantly higher incidence of sarcopenic (p = 0.006), visceral (p < 0.001) and subcutaneous obesity (p < 0.001). Patients with MAFLD had longer time‐to‐recurrence (median: 38 vs. 12 months, p = 0.025, log‐rank test). Multivariable cox regression analysis confirmed only clinical, and not body, composition parameters (age > 65, fresh frozen plasma transfusions) as independently prognostic for overall survival. Conclusion: This study evidenced a high prevalence of MAFLD in iCCA, suggesting its potential contribution to disease aetiology. Alterations of muscle mass and adipose tissue were more frequent in patients with MAFLD. [ABSTRACT FROM AUTHOR]