Impact of Donor Age on Liver Transplant Outcomes in Patients with Acute-on-Chronic Liver Failure: A Cohort Study.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age into group I (donor age ≤17 years, n=647); group II (donor age 18-59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were compared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001). When we analyzed the different effects of donor age on OS with different ACLF grades, in groups II and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions: Donor age is related to OS and graft survival of ACLF patients after transplantation, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

The impact of Karnofsky performance status on prognosis of patients with hepatocellular carcinoma in liver transplantation.

BACKGROUND: Functional performance as measured by the Karnofsky Performance Status (KPS) scale has been linked to the outcomes of liver transplant patients; however, the effect of KPS on the outcomes of the hepatocellular carcinoma (HCC) liver transplant population has not been fully elucidated. We aimed to investigate the association between pre-transplant KPS score and long-term outcomes in HCC patients listed for liver transplantation. METHODS: Adult HCC candidates listed on the Scientific Registry of Transplant Recipients (SRTR) database from January 1, 2011 to December 31, 2017 were grouped into group I (KPS 80-100%, n = 8,379), group II (KPS 50-70%, n = 8,091), and group III (KPS 10-40%, n = 1,256) based on percentage KPS score at listing. Survival was compared and multivariable analysis was performed to identify independent predictors. RESULTS: Patients with low KPS score had a higher risk of removal from the waiting list. The 5-year intent-to-treat survival was 57.7% in group I, 53.2% in group II and 46.7% in group III (P < 0.001). The corresponding overall survival was 77.6%, 73.7% and 66.3% in three groups, respectively (P < 0.001). Multivariable analysis demonstrated that KPS was an independent predictor of intent-to-treat survival (P < 0.001, reference group I; HR 1.19 [95%CI 1.07-1.31] for group II, P = 0.001; HR 1.63 [95%CI 1.34-1.99] for group III, P < 0.001) and overall survival(P < 0.001, reference group I; HR 1.16 [95%CI 1.05-1.28] for group II, P = 0.004; HR 1.53 [95%CI 1.26-1.87] for group III, P < 0.001). The cumulative 5-year recurrence rates was higher in group III patients (7.4%), compared with 5.2% in group I and 5.5% in group II (P = 0.037). However, this was not significant in the competing regression analysis. CONCLUSIONS: Low pre-transplant KPS score is associated with inferior long-term survival in liver transplant HCC patients, but is not significantly associated with post-transplant tumor recurrence.

Impact of donor diabetes mellitus status on liver transplant outcomes in patients with acute-on-chronic liver failure.

BACKGROUND: Liver transplantation (LT) is the most effective way to save patients with acute-on-chronic liver failure (ACLF). However, the impact of donor diabetes mellitus (DM) on LT outcomes in patients with ACLF has not been fully investigated. RESEARCH DESIGN AND METHODS: We retrospectively analyzed data from the Scientific Registry of Transplant Recipients (SRTR) between January 1st, 2008 to December 31st, 2017 in this study. All the patients were divided into donors with DM and without DM group (DM: 1,394; non-DM: 11138). We compared the overall survival (OS) and graft survival (GS) across different estimated ACLF (estACLF) grades between two groups. RESULTS: There were 25.10% estACLF-3 patients in the entire cohort. And in estACLF-3 patients, 318 patients had DM donors. The estACLF-3 associated 5-year OS rate in the non-DM group was 74.6%, significantly better than that in the DM group, with corresponding survival rate at 64.9% (P < 0.001). Donor DM was an independent predictor for OS in the entire cohort as well as in estACLF-3 patients. CONCLUSIONS: Donor DM was associated with inferior outcomes of LT in patients with estACLF-3. However, the differences were not obvious in recipients with other estACLF grades.

The interaction of T2DM and BMI with NASH in recipients of liver transplants: an SRTR database analysis.

BACKGROUND: NASH-related liver transplants are increasing because of the obesity epidemic, but the influence of T2DM on various levels of BMI among NASH recipients is unclear. RESEARCH DESIGN AND METHODS: We analyzed data retrieved from SRTR on 4,515 patients. We divided patients by BMI into five groups: normal weight; overweight; class 1 obesity; class 2 obesity; and class 3 obesity. Statistical analysis was done. RESULTS: Patients in the NASH group with T2DM had a lower patient and graft survival than patients without T2DM (5-year patient and graft survival: 77.5% vs. 79.8%; P = 0.001 and 76.4% vs. 78.2%; P = 0.002, respectively). Multivariate Cox proportional regression showed an independent association between T2DM and decreased patient and graft survival (HR, 1.170; P = 0.015 and HR, 1.133; P = 0.048, respectively). In the lean and the class 3 obesity NASH groups, patients with T2DM had lower patient and graft survival than the patients without T2DM. In the class 3 obesity NASH group, T2DM was independently associated with decreased patient survival (HR, 1.581; P = 0.027). CONCLUSION: Our research reveals that the focus of the post-transplantation treatment should be different for different BMI patients.

Antioxidative and Energy Metabolism-Improving Effects of Maca Polysaccharide on Cyclophosphamide-Induced Hepatotoxicity Mice via Metabolomic Analysis and Keap1-Nrf2 Pathway.

Lepidium meyenii Walp. (Maca), as a natural food supplement, has strong antioxidant and energy metabolism-improving characteristics, and Maca polysaccharide (MP) is its effective component. MP has been shown to mitigate liver damage in previous research, and Cyclophosphamide (CYP)-induced hepatotoxicity is also a major concern in clinical practice. We investigated the possible cytoprotective effect of MP on CYP-induced liver injury, and explored its underlying mechanism by analyzing the resulting liver metabolic profiles. MP significantly inhibited increases in serum transaminase, improved pathological changes, reduced oxidative stress, and increased the levels of energy metabolism-related enzymes. Metabolomic analysis showed that MP corrected lipid metabolic problems and regulated the pentose phosphate pathway and acid metabolism, thereby protecting against apoptosis of hepatocytes. The Pearson correlation analysis indicated that antioxidant enzymes and energy metabolism-related enzymes are closely correlated with these differential metabolites. In addition, the upstream Keap1-Nrf2 antioxidant signal transduction pathway was explored to validate the possible mechanism of the cytoprotective effect of MP. In conclusion, MP plays a protective role in CYP-induced hepatotoxicity through these potential metabolic means, where it ameliorates oxidative stress, improves energy metabolism, and restores mitochondrial respiration by regulating the Keap1-Nrf2 signaling pathway, thereby preventing liver damage.

Evaluation of retinal vessel and perfusion density in migraine patients by optical coherence tomography angiography.

BACKGROUND: Migraine is a neurovascular disease and has been reported as a risk factor for ocular vascular complications. Our study aimed to compare the retinal vessel density and perfusion density between migraine patients and healthy subjects by optical coherence tomography angiography (OCTA). METHODS: In this prospective study, 23 patients with migraine with aura (MWA) and 31 patients with migraine without aura (MWOA), and 32 age- and gender-matched healthy controls (HC) were enrolled. The vessel density (VD) and perfusion density (PD) were evaluated in a 6 × 6 mm scan of the macula and optic nerve head (ONH) with the Cirrus HD-OCT 5000 device. The measurement area is divided into three areas: center (c), inner ring (ir), outer ring (or) (with diameters of 1, 3, and 6 mm respectively), and nine subfields, according to the Early Treatment Retinopathy Study grid. RESULTS: The macular cVD, cPD, and temporal orVD in MWA and MWOA groups were significantly reduced than those of HC. On optic nerve head OCTA, patients with MWA had decreased cVD, average irVD, inferior irVD, and temporal orVD compared with HCs while MWOA had reduced cVD than HC group. In addition, PD was not significantly different among MWA, MWOA, and HC groups in any measure in the optic nerve head. The Migraine Disability Assessment Score (MIDAS) and attack frequency were significantly inversely correlated with cVD, cPD, irVD, and irPD of macula and ONH. CONCLUSIONS: Vessel and perfusion density of macula were reduced in both MWA and MWOA. Vessel density, but not perfusion density of ONH was decreased in MWA. The migraine severity and attack frequency were significantly inversely correlated with vessel and perfusion density of macula and ONH.

miR-296-5p Inhibits the Secretion of Pulmonary Surfactants in Pulmonary Epithelial Cells via the Downregulation of Wnt7b/ß-Catenin Signaling.

Neonatal respiratory distress syndrome (NRDS) is a common disease that occurs in premature infants. However, the mechanisms underlying the disease remain unclear. microRNAs (miRNAs) have been indicated to play a crucial role in the development of NRDS. In this study, we aimed to explore the regulatory mechanisms of miR-296-5p in NRDS. The expression levels of miR-296-5p in preterm infants with NRDS were determined using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). A549 cells were transfected with lentiviral vectors encoding miR-296-5p, and the transfection efficiency was determined using RT-qPCR. Flow cytometry and CCK8 assay were performed to measure apoptosis and proliferation of A549 cells, respectively. The protein levels of pulmonary surfactant SP-A (SFTPA1), SP-B, Wnt7b, and ß-catenin were measured using western blotting. We demonstrated an upregulation of miR-296-5p in NRDS. The miR-296-5p was successfully overexpressed in A549 cells via lentivirus transfection, and the upregulation of miR-296-5p inhibited cell proliferation and secretion of SP-A and SP-B and also induced downregulation of the Wnt7b/ß-catenin in vitro. Therefore, miR-296-5p inhibits cell proliferation and secretion of pulmonary surfactants in A549 cells via downregulation of Wnt7b/ß-catenin signaling.

Fructo-oligosaccharides lower serum lipid levels and suppress high-fat/high-sugar diet-induced inflammation by elevating serum and gut levels of short-chain fatty acids.

OBJECTIVE: This study aimed to investigate the effects of fructo-oligosaccharides (FOS) on serum lipid levels and to determine the mechanisms underlying these effects and the potential role of inflammation. METHODS: Male C57BL/6 mice received a normal diet, a high-fat/high-sugar (HFS) diet, or an HFS diet supplemented with 10% FOS for 10 weeks. In vivo intestinal and serum short-chain fatty acid (SCFA) levels were measured by gas chromatography. In vivo serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malonaldehyde (MDA) were also measured. Lipid accumulation was visualized. Reactive oxygen species (ROS) generation was evaluated and apoptosis was quantified. RESULTS: FOS reversed in vivo HFS-induced lipid accumulation in the liver. An HFS diet increased ALT, AST, TC, TG, and LDL serum levels, decreased HDL serum levels, and increased IL-6, TNF-α, 8-OHdG, and MDA levels. These changes were reduced by FOS. FOS also increased intestinal and serum levels of short chain fatty acids (SCFAs). In vitro, SCFAs ameliorated palmitic acid-induced ROS production and apoptosis of HepG2 cells. CONCLUSION: FOS supplementation lowers serum lipid levels and ameliorates HFS-induced inflammation by upregulating SCFAs.