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Search Results (471)

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Keywords = end-stage liver disease

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16 pages, 2053 KB  
Article
Chronic and Heavy Drinking, Nutrition Status, and Progression of Liver Injury Negatively Affect the Mortality Risk in Patients Suffering from Alcohol-Associated Hepatitis
by Aishwarya Thakurdesai, Anjali Kumari, Henry Shay, Khaled Elgharabawy, Evan J. Winrich, Wanyu Zhang, Amber Jackson, Matthew C. Cave, Maiying Kong, Xiang Zhang, Ashwani K. Singal, Craig J. McClain and Vatsalya Vatsalya
J. Clin. Med. 2025, 14(17), 6157; https://doi.org/10.3390/jcm14176157 (registering DOI) - 31 Aug 2025
Abstract
Background/Objectives: Alcohol-associated hepatitis (AH) is an acute inflammatory condition of alcohol-associated liver disease (ALD) with rapid progression and high mortality. The Age-Bilirubin-INR-Creatinine (ABIC) score is a static algorithm that predicts survivability in AH. The roles of alcohol drinking patterns and nutritional status [...] Read more.
Background/Objectives: Alcohol-associated hepatitis (AH) is an acute inflammatory condition of alcohol-associated liver disease (ALD) with rapid progression and high mortality. The Age-Bilirubin-INR-Creatinine (ABIC) score is a static algorithm that predicts survivability in AH. The roles of alcohol drinking patterns and nutritional status in AH progression and risk of death are understudied. This study evaluates the impact of alcohol drinking patterns and nutrition on AH progression and mortality. Methods: Sixty-one adult patients diagnosed with AH were stratified by the Model for End-Stage Liver Disease (MELD) as non-severe (MELD < 20, n = 26, Gr.1) and severe (MELD ≥ 20, n = 35, Gr.2). Each group was further subdivided by ABIC: low- (<6.71), intermediate- (6.71–9), and high- (>9) risk categories. We assessed different demographics: nutrition using the Controlling Nutritional Status (CONUT) score; lifetime drinking history (LTDH); recent alcohol use (AUDIT); laboratory measures (complete metabolic panel, complete blood count, and coagulation), and clinical measures (Maddrey DF, Child–Turcotte–Pugh, and Lille). Results: All patients showed a significant and positive correlation between ABIC and LTDH (r = 0.538, p = 0.004), particularly in Gr.2 (r = 0.554, p = 0.011). The low-risk Gr.2 exhibited the highest AST:ALTs. AST:ALTs were significantly associated with LTDH, AUDIT, and CONUT (R2 = 0.539, p = 0.031). In all AH patients with intermediate mortality risk, AST:ALTs were strongly linked to CONUT and LTDH (R2 = 0.657, p = 0.017). Conclusions: Severe AH demonstrates rapid liver injury progression even when the mortality risk is low. Chronic and recent heavy alcohol consumption and poor nutrition adversely impact AH severity and mortality risk. Alcohol intake and nutritional assessments in routine clinicals could identify high-risk patients, thereby improving treatment and a favorable prognosis. Full article
(This article belongs to the Special Issue Alcohol-Related Liver Disease: Diagnosis, Treatment, and Management)
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13 pages, 2048 KB  
Article
Dual Energy CT-Derived Liver Extracellular Volume Fraction for Assessing Liver Functional Reserve in Patients with Liver Cirrhosis
by Seok Jin Hong, Ji Eun Kim, Jae Min Cho, Ho Cheol Choi, Mi Jung Park, Hye Young Choi, Hwa Seon Shin, Jung Ho Won, Wonjeong Yang and Hyun Ok Kim
Medicina 2025, 61(9), 1561; https://doi.org/10.3390/medicina61091561 - 30 Aug 2025
Viewed by 95
Abstract
Background and Objectives: The extracellular volume fraction (fECV) of the liver, as measured by contrast-enhanced computed tomography (CT), has been shown to correlate closely with the histological stages of hepatic fibrosis. This study aimed to investigate the diagnostic performance of a liver [...] Read more.
Background and Objectives: The extracellular volume fraction (fECV) of the liver, as measured by contrast-enhanced computed tomography (CT), has been shown to correlate closely with the histological stages of hepatic fibrosis. This study aimed to investigate the diagnostic performance of a liver extracellular volume fraction derived from dual-energy CT (DECT) for evaluating liver functional reserve based on the Child–Pugh class in cirrhotic patients, compared with other noninvasive markers. Materials and Methods: This retrospective study included 258 patients with liver cirrhosis who underwent contrast-enhanced DECT. The fECV was measured using iodine maps derived from equilibrium phase images obtained 3 min after contrast injection at 100/140 Sn kVp. Statistical analyses included Welch’s ANOVA with post hoc tests, Spearman’s correlation, and ROC analysis. The area under the curve (AUC) was compared among fECV and other noninvasive markers (aspartate transaminase to platelet ratio index [APRI], Fibrosis-4 [FIB-4], and model for end-stage liver disease [MELD]) using DeLong’s test. Intra- and interobserver reliability of fECV was assessed with the intraclass correlation coefficient (ICC). The area under the receiver operating characteristic curve (AUC) for differentiating Child–Pugh classes was compared among the fECV and other noninvasive markers (aspartate transaminase to platelet ratio index [APRI], Fibrosis-4 [FIB-4], and model for end-stage liver disease [MELD]). Results: The fECV increased significantly with advancing Child–Pugh classes (p < 0.001), showing a moderate correlation with Child–Pugh class (r = 0.53). The mean differences in fECV among the Child–Pugh classes were 8.88 between A and B (95% confidence interval [CI], 5.85–11.92; p < 0.001) and 7.42 between B and C (95% CI, 1.92–12.91: p < 0.001). The AUC for differentiating Child–Pugh classes A and B demonstrated no significant differences among the fECV (0.84), APRI (0.83, p > 0.99) and FIB-4 (0.83, p > 0.99), except for MELD, which had a significantly higher AUC (0.94, p = 0.047). For differentiating Child-Pugh classes B and C, the fECV demonstrated a significantly higher AUC (0.78), compared with FIB-4 (0.50, p = 0.038) and APRI (0.49, p = 0.037), whereas no significant difference was observed between fECV and MELD (0.92, p = 0.12). The intra- and interobserver reliabilities of the fECV measurements were excellent (ICC, 0.93; 95% CI, 0.91–0.95 and 0.91; 95% CI, 0.88–0.92, respectively). Conclusions: DECT derived fECV is a useful noninvasive marker for assessing liver functional reserve based on the Child–Pugh classification. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
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13 pages, 763 KB  
Review
Palliative Care in End-Stage Liver Disease
by Luisa Sousa, Sofia Marques Silva, Francisca Rego, Rui Nunes and Hugo M. Oliveira
Livers 2025, 5(3), 39; https://doi.org/10.3390/livers5030039 - 22 Aug 2025
Viewed by 694
Abstract
Chronic liver disease is a significant global cause of morbidity and mortality. While early-stage liver cirrhosis is often asymptomatic, it can progress to a decompensated phase known as end-stage liver disease (ESLD), resulting in a high symptom burden, diminished quality of life, and [...] Read more.
Chronic liver disease is a significant global cause of morbidity and mortality. While early-stage liver cirrhosis is often asymptomatic, it can progress to a decompensated phase known as end-stage liver disease (ESLD), resulting in a high symptom burden, diminished quality of life, and frequent hospitalizations. Palliative care is a form of specialized care aimed at addressing the needs of patients; however, it remains underutilized in ESLD patients. Globally, the integration of palliative care into ESLD is impeded by several barriers. Certain factors—such as advanced age, the presence of hepatocellular carcinoma (HCC), and transplant listing status—have been associated with higher rates of palliative care referral. This review provides a comprehensive analysis of the current literature, emphasizing the benefits of palliative care interventions in ESLD, including improved symptom control and enhanced quality of life. It also underscores the impact on caregivers and healthcare systems, notably in reducing hospital readmissions. We advocate for a paradigm shift toward proactive, patient-centered models that integrate symptom management, advance care planning, and psychosocial support alongside disease-specific treatments for patients with ESLD. Full article
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14 pages, 661 KB  
Article
Comparative Analysis of Multi-Organ Failure Trajectories Following Heart Transplantation and HeartMate 3 Implantation: A 1-Year Postprocedural Follow-Up Study Utilizing the MELD-XI Scale
by Mateusz Sokolski, Jakub Ptak, Małgorzata Makieła, Maciej Szwajkowski, Mateusz Waloszczyk, Kacper Wiśniewski, Joanna Gontarczyk, Paulina Makowska, Dominik Krupka, Natalia Sitko, Magdalena Cielecka, Mateusz Rakowski, Maciej Bochenek, Roman Przybylski and Michał Zakliczyński
J. Clin. Med. 2025, 14(17), 5933; https://doi.org/10.3390/jcm14175933 - 22 Aug 2025
Viewed by 318
Abstract
Background: Multi-organ failure (MOF) is a common complication of advanced heart failure (HF), significantly influencing patient prognosis. This study aimed to assess and compare the impact of orthotopic heart transplantation (HTx) and left ventricular assist device (LVAD) implantation on the severity of [...] Read more.
Background: Multi-organ failure (MOF) is a common complication of advanced heart failure (HF), significantly influencing patient prognosis. This study aimed to assess and compare the impact of orthotopic heart transplantation (HTx) and left ventricular assist device (LVAD) implantation on the severity of MOF, as measured by the model for end-stage liver disease excluding INR (MELD-XI) score. Methods: Data from 1 month before to 1 year after HTx or LVAD implantation were analysed. The MELD-XI score was calculated using average bilirubin and creatinine values. Comparative assessments of MELD-XI scores were performed within the HTx and LVAD groups at various time points pre- and post-procedure. Results: The analysis included 107 HTx patients and 30 LVAD patients. The median MELD-XI score 1 month pre-procedure was 11.7 (9.4–16.7) in all patients. There were no significant differences in MELD-XI scores between the groups at 3-, 6-, and 12-month follow-ups. However, a significant difference was observed 1 month post-procedure [HTx: 14.8 (9.4–17.7) vs. LVAD: 11.2 (7.3–14.9), p = 0.02]. In the LVAD group, a significant decrease in MELD-XI score was noted for 3 months post-procedure compared to 1 month pre-procedure (p < 0.001), whereas at 6- and 12-month follow-ups the score did not differ from pre-procedural scores. In the HTx group, significant decreases in MELD-XI scores were observed from 3 months, 6 months, and 1 year post-procedure compared to 1 month pre-procedure (p < 0.002). Conclusions: The MELD-XI scale reveals different MOF trajectories between HTx and LVAD recipients. Both interventions lead to early improvements in liver and kidney function, with sustained benefits in HTx patients, highlighting the distinct impacts on organ function. Full article
(This article belongs to the Special Issue Clinical Updates in Heart Transplantation)
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12 pages, 596 KB  
Article
Model for End-Stage Liver Disease Excluding INR Is Associated with Poor Prognosis in Elderly Patients with Decompensated Heart Failure
by Michał Jurkiewicz, Wioletta Szczurek-Wasilewicz, Michał Skrzypek, Jacek J. Jóźwiak, Mariusz Gąsior and Bożena Szyguła-Jurkiewicz
Biomedicines 2025, 13(8), 2000; https://doi.org/10.3390/biomedicines13082000 - 18 Aug 2025
Viewed by 373
Abstract
Introduction: Heart failure (HF) remains a leading cause of morbidity and hospitalization among elderly patients. Therefore, identifying reliable prognostic indicators is crucial for improving clinical outcomes in this population. The aim of this study was to evaluate the association between the Model for [...] Read more.
Introduction: Heart failure (HF) remains a leading cause of morbidity and hospitalization among elderly patients. Therefore, identifying reliable prognostic indicators is crucial for improving clinical outcomes in this population. The aim of this study was to evaluate the association between the Model for End-stage Liver Disease excluding INR (MELD-XI) and clinical outcomes in elderly patients hospitalized for decompensated HF. Material and methods: This was a single-center observational study involving 242 elderly patients with end-stage HF who were hospitalized for decompensation at our institution between 2019 and 2023. Upon hospital admission and discharge, MELD-XI scores were calculated using serum bilirubin and creatinine levels. The primary endpoint of the study was all-cause mortality during the follow-up period. Results: The median age of the patients was 68 years (66–74.6), and 78.9% were men. The median (Q1–Q3) follow-up time was 1.47 (0.78–2.31) years. During the follow-up period, 47.1% of the patients died. Independent predictors of mortality were diabetes mellitus [HR 1.656 (1.113–2.463), p = 0.013] and MELD-XI at discharge [OR 1.267 (1.210–1.327), p < 0.001]. The area under the receiver operating characteristic curves (AUC) for MELD-XI at discharge was 0.827 (95% CI: 0.776–0.878). The cut-off value for MELD-XI at discharge (>11.7 points) had a sensitivity of 97% and a specificity of 59%. Conclusions: Independent predictors of death in the analyzed population of elderly patients with decompensated HF were diabetes mellitus and MELD-XI at discharge. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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15 pages, 1728 KB  
Review
MicroRNAs in Liver Cirrhosis: Diagnostic and Therapeutic Perspectives—A Comprehensive Review
by Cristian Ichim, Adrian Boicean, Paula Anderco, Samuel Bogdan Todor, Adrian Hașegan, Sabrina Bîrsan and Victoria Bîrluțiu
J. Pers. Med. 2025, 15(8), 376; https://doi.org/10.3390/jpm15080376 - 14 Aug 2025
Viewed by 334
Abstract
Liver cirrhosis represents the end-stage of chronic hepatic injury, arising from a diverse range of etiologies including viral hepatitis, alcohol abuse and non-alcoholic fatty liver disease. A key driver of cirrhosis is hepatic fibrogenesis, a multifaceted process involving hepatic stellate cell activation, inflammatory [...] Read more.
Liver cirrhosis represents the end-stage of chronic hepatic injury, arising from a diverse range of etiologies including viral hepatitis, alcohol abuse and non-alcoholic fatty liver disease. A key driver of cirrhosis is hepatic fibrogenesis, a multifaceted process involving hepatic stellate cell activation, inflammatory signaling and extracellular matrix accumulation. MicroRNAs (miRNAs), a class of small non-coding RNAs, have emerged as pivotal regulators in this context, modulating gene expression networks that govern inflammation, fibrosis and hepatocarcinogenesis. This review synthesizes current evidence on the role of miRNAs in liver cirrhosis, emphasizing specific miRNAs such as miR-21, miR-122, miR-125, miR-146 and miR-155. These miRNAs influence pathways involving TGF-β, NF-κB and PI3K/Akt signaling, contributing to either fibrogenic progression or its suppression. The unique expression profiles and stability of miRNAs in biological fluids position them as promising non-invasive biomarkers for cirrhosis diagnosis and monitoring. Moreover, therapeutic modulation of miRNA activity through mimics or inhibitors holds future potential, though delivery and safety challenges remain. Advancing our understanding of miRNA-mediated regulation in cirrhosis could transform current diagnostic and therapeutic strategies, enabling more precise and personalized liver disease management. Full article
(This article belongs to the Section Disease Biomarker)
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14 pages, 233 KB  
Article
Ten-Year Trends in Hepatocellular Carcinoma Mortality: Examining the Interaction Between Fibrosis Score and Patient Age
by Ayrton Bangolo, Hadrian Hoang-Vu Tran, Budoor Alqinai, Rishabh Goyal, Shehwar Ahmed, Aamna Qasim, Gabriela Rojas, Shubham Madan, Helena Barbosa, Zainab Mustafa, Risham Waseem, Gabriel Ingersoll, Hamza Khan, Alison Guzzetti, Jonathan Daniel, Samiya Parkar, Aakriti Tiwari, Sarah Lafleur, Rajasekhar Cingapagu, Saliha Y. Amasyali, Eric Pin-Shiuan Chen and Simcha Weissmanadd Show full author list remove Hide full author list
Diseases 2025, 13(8), 256; https://doi.org/10.3390/diseases13080256 - 12 Aug 2025
Viewed by 421
Abstract
Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with survival outcomes influenced by a range of demographic and pathological factors. While cirrhosis is a well-established risk factor, recent evidence shows that HCC can also develop in patients with only [...] Read more.
Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with survival outcomes influenced by a range of demographic and pathological factors. While cirrhosis is a well-established risk factor, recent evidence shows that HCC can also develop in patients with only mild to moderate liver fibrosis. However, there is limited understanding of how fibrosis severity interacts with other clinical variables, such as patient age, to affect mortality. This study aims to explore how fibrosis scores relate to both overall and cancer-specific mortality in US HCC patients, with an emphasis on how this relationship may shift across different age groups. Methods: We utilized data from the Surveillance, Epidemiology, and End Results (SEER) database to identify 15,796 adult patients diagnosed with HCC between 2010 and 2021. Baseline demographics, disease characteristics, and treatment variables were examined. Mortality outcomes were evaluated using Cox proportional hazard regression. Variables significant at p < 0.1 in univariate analysis were included in multivariate models to identify independent predictors of mortality (with hazard ratios [HRs] > 1 signifying increased risk). A secondary analysis assessed how age modifies the association between fibrosis score and mortality. Results: The study population was predominantly male (77.2%), with most patients aged 60–79 (59.6%) and presenting with localized disease (61%). A majority had advanced liver fibrosis or cirrhosis (81.7%) and lived in large urban areas (62.9%). Crude comparisons indicated that male sex, older age, single status, advanced tumor stage, lower income, and cirrhosis were linked to worse outcomes. In adjusted models, independent predictors of increased mortality included male sex, older age, unmarried status, and more advanced disease stage. Receipt of surgery or chemotherapy was associated with a lower risk of death. Notably, the influence of fibrosis on mortality was found to be greater in older patients than in their younger counterparts. Conclusions: This analysis identifies key prognostic indicators in HCC and suggests that the relationship between fibrosis and survival is not uniform across age groups. These findings support the need for age-specific clinical management strategies and highlight the potential benefit of early detection and appropriate interventions, even in non-cirrhotic patients. Full article
15 pages, 1484 KB  
Article
High-Risk PNPLA3 rs738409 Genotype Is Associated with Higher Concentrations of CCL2 in Liver Transplant Candidates with Alcoholic End-Stage Liver Disease
by Ivan Budimir Bekan, Dino Šisl, Alan Šućur, Ana Bainrauch, Valerija Bralić Lang, Pavao Planinić, Nataša Kovačić, Danka Grčević, Anna Mrzljak and Tomislav Kelava
Medicina 2025, 61(7), 1293; https://doi.org/10.3390/medicina61071293 - 18 Jul 2025
Viewed by 446
Abstract
Background and Objectives: Patients with GG rs738409 patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype (148M variant) have greater risk to develop end-stage liver disease and its associated clinical complications, including hepatocellular carcinoma (HCC). We aimed to analyze the association between the PNPLA3 [...] Read more.
Background and Objectives: Patients with GG rs738409 patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype (148M variant) have greater risk to develop end-stage liver disease and its associated clinical complications, including hepatocellular carcinoma (HCC). We aimed to analyze the association between the PNPLA3 genotype and augmented inflammatory response in transplant candidates with end-stage alcoholic liver disease (ALD). Materials and Methods: Concentrations of 13 cytokines were measured in 106 end-stage ALD patients without HCC (40 with CC, 40 with CG, and 26 with GG genotype), 35 end-stage ALD patients with HCC, and 19 control patients by cytometric bead array. Results: We found significantly higher concentrations of IL-1, IFN-α, IFN-γ, TNF-α, IL-6, CXCL8, IL-10, IL-12, IL-32, and IL-33 in patients with ALD compared to controls, while the concentration of CCL2 was significantly lower. No differences were observed in the concentration of IL-17 and IL-18. ALD patients with and without HCC had similar cytokine concentrations (p > 0.05 for all comparisons). End-stage ALD patients without HCC of the GG genotype had significantly higher CCL2 concentrations (212.6 [135.9–264.9] pg/mL) compared to end-stage ALD patients without HCC carrying the CC/CG genotypes (141.3 [104.1–201.6] pg/mL, p = 0.002, Mann–Whitney). No significant differences across the genotypes were found for the remaining measured cytokines (p > 0.05). GG carriers also had significantly higher levels of AST and ALT, and lower platelet counts. Conclusions: End-stage ALD patients without HCC who carry the PNPLA3 GG genotype have relatively higher CCL2 levels compared to those with the CC or CG genotypes. Relatively elevated CCL2 concentrations in GG patients might contribute to their increased risk of developing clinical complications compared to CC/CG patients. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Treatment of Chronic Liver Disease)
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18 pages, 1149 KB  
Article
Hypothermic Machine Perfusion Is Associated with Improved Short-Term Outcomes in Liver Transplantation: A Retrospective Cohort Study
by Alexandru Grigorie Nastase, Alin Mihai Vasilescu, Ana Maria Trofin, Mihai Zabara, Ramona Cadar, Ciprian Vasiluta, Nutu Vlad, Bogdan Mihnea Ciuntu, Corina Lupascu Ursulescu, Cristina Muzica, Irina Girleanu, Iulian Buzincu, Florin Iftimie and Cristian Dumitru Lupascu
Life 2025, 15(7), 1112; https://doi.org/10.3390/life15071112 - 16 Jul 2025
Viewed by 707
Abstract
Introduction: Liver transplantation remains the definitive treatment for end-stage liver disease but faces critical challenges including organ shortages and preservation difficulties, particularly with extended criteria donor (ECD) grafts. Hypothermic machine perfusion (HMP) represents a promising alternative to traditional static cold storage (SCS). Methods: [...] Read more.
Introduction: Liver transplantation remains the definitive treatment for end-stage liver disease but faces critical challenges including organ shortages and preservation difficulties, particularly with extended criteria donor (ECD) grafts. Hypothermic machine perfusion (HMP) represents a promising alternative to traditional static cold storage (SCS). Methods: This retrospective study analyzed outcomes from 62 liver transplant recipients between 2016 and 2025, comparing 8 grafts preserved by HMP using the Liver Assist® system and 54 grafts preserved by SCS. Parameters assessed included postoperative complications, hemodynamic stability, ischemia times, and survival outcomes. Results: HMP significantly reduced surgical (0% vs. 75.9%, p = 0.01) and biliary complications (0% vs. 34.4%, p = 0.004), improved hemodynamic stability post-reperfusion (∆MAP%: 1 vs. 21, p = 0.006), and achieved superior one-year survival rates (100% vs. 84.4%). Despite longer ischemia periods, grafts treated with HMP exhibited fewer adverse effects from ischemia-reperfusion injury. Discussion: These findings highlight the substantial benefits of HMP, particularly in improving graft quality from marginal donors and reducing postoperative morbidity. Further adoption of this technology could significantly impact liver transplantation outcomes by expanding the viable donor pool. Conclusions: The study underscores the effectiveness of hypothermic machine perfusion (HMP) as a superior preservation method compared to traditional static cold storage (SCS), HMP appears to be associated with improved short-term outcomes in liver transplantation. By substantially reducing postoperative complications and enhancing graft viability, HMP emerges as a pivotal strategy for maximizing the use of marginal donor organs. Further research and broader clinical implementation are recommended to validate these promising results and to fully harness the potential of HMP in liver transplantation. Full article
(This article belongs to the Section Medical Research)
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24 pages, 8054 KB  
Article
INHIBITION OF THE PROSTAGLANDIN-DEGRADING ENZYME 15-PGDH AMELIORATES MASH-ASSOCIATED APOPTOSIS AND FIBROSIS IN MICE
by Utibe-Abasi S. Udoh, Mathew Steven Schade, Jacqueline A. Sanabria, Pradeep Kumar Rajan, Rodrigo Aguilar, Micheal Andryka, Alexei Gorka, Sandrine V. Pierre and Juan Sanabria
Cells 2025, 14(13), 987; https://doi.org/10.3390/cells14130987 - 27 Jun 2025
Viewed by 3593
Abstract
Background. Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world population. Progression to its inflammatory state, MASH, is associated with increasing liver fibrosis, leading to end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC). SW033291, an inhibitor of 15-PGDH [...] Read more.
Background. Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world population. Progression to its inflammatory state, MASH, is associated with increasing liver fibrosis, leading to end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC). SW033291, an inhibitor of 15-PGDH (the PGE2 degradation enzyme), has been shown to increase in vivo regeneration of liver parenchyma, ameliorating oxidative stress and inflammation. We hypothesized that SW033291 abrogates MASH progression by inducing a paucity of the initial apoptotic switch and restoring physiological collagen’s microenvironment. Methods. The expression levels of the cell metabolic proteins FOXO1, mTOR, and SIRT7 were determined in a diet-induced MASH-mouse model at 16, 20, and 24 weeks. Non-targeted metabolomics in mouse plasma were measured by LC-MS/MS. Liver morphology and apoptotic activity were quantified by the NAS score and TUNEL assay, respectively. Statistical analyses between groups (NMC, HFD, and SW033291) were determined by ANOVA, t-test/Tukey’s post hoc test using GraphPad Prism. Metabolomics data were analyzed using R-lab. Results. The treated group showed significant decreases in total body fat, cellular oxidative stress, and inflammation and an increase in total lean mass with improved insulin resistance and favorable modulation of metabolic protein expressions (p < 0.05). SW033291 significantly decreased GS:SG, citric acid, and corticosterone, NAS scores (9.4 ± 0.2 vs. 6.2 ± 0.1, p < 0.05), liver fibrosis scores (1.3 ± 0.5 vs. 0.25 ± 0.1, p < 0.05), and apoptotic activity (43.9 ± 4.6 vs. 0.38 ± 0.1%, p < 0.05) compared with controls at 24W. Conclusions. The inhibition of 15-PGDH appears to normalize the metabolic and morphological disturbances during MASH progression with a paucity of the initial apoptotic switch, restoring normal collagen architecture. SW033291 warrants further investigation for its translation. Full article
(This article belongs to the Special Issue Cellular Pathology: Emerging Discoveries and Perspectives in the USA)
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12 pages, 682 KB  
Article
Sina Score as a New Machine Learning-Derived Online Prediction Model of Mortality for Cirrhotic Patients Awaiting Liver Transplantation: A Prospective Cohort Study
by Seyed Mohammad Kazem Hosseini-Asl, Seyed Jalil Masoumi, Ghazaleh Rashidizadeh, Amir Hossein Hassani, Golnoush Mehrabani, Vahid Ebrahimi, Seyed Ali Malek-Hosseini, Saman Nikeghbalian and Alireza Shakibafard
J. Clin. Med. 2025, 14(13), 4559; https://doi.org/10.3390/jcm14134559 - 27 Jun 2025
Viewed by 490
Abstract
Background: Cirrhosis is responsible for a large proportion of mortality worldwide. Despite having multiple scoring systems, organ allocation for end-stage liver disease remains a major problem. Since anthropometric indices play important roles in predicting the prognosis of patients with cirrhosis, these variables were [...] Read more.
Background: Cirrhosis is responsible for a large proportion of mortality worldwide. Despite having multiple scoring systems, organ allocation for end-stage liver disease remains a major problem. Since anthropometric indices play important roles in predicting the prognosis of patients with cirrhosis, these variables were used in establishment of a novel scoring system. Methods: In order to evaluate a machine learning approach for predicting the probability of three-month mortality in cirrhotic patients awaiting liver transplantation, the clinical and anthropometric information of 64 patients referred to Abu-Ali-Sina Transplantation Center were collected and followed for three months. A LASSO logistic regression model was used to devise and validate a new machine learning approach and compare it to the Model for End-Stage Liver Disease (MELD) regarding the three-month mortality of cirrhotic patients. Hand grip, skeletal muscle mass index, average mean arterial pressure, serum sodium, and total bilirubin were assessed with this new machine learning approach to predict the prognosis of patients with cirrhosis, which we named the Sina score. Results: Sixty-four patients were enrolled, with a mean age of 46.50 ± 12.871 years. Like the MELD score, the Sina score is a precise prognostic tool for predicting the three-month mortality probability in cirrhotic patients [area under the curve (AUC) = 0.753 and p = 0.005 vs. AUC = 0.607 and p = 0.238]. Our machine learning approach, the Sina score, was shown to be a precise prognostic tool, like the MELD, for the prediction of the three-month mortality probability of cirrhotic patients awaiting liver transplantation. Conclusions: The Sina score, given that its level of precision is on par with the MELD, can be recommended for the prediction of three-month mortality in cirrhotic patients awaiting liver transplantation. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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11 pages, 394 KB  
Article
Fetuin-A Can Assess the Severity of Alcohol-Related Liver Disease
by Musa Salmanoğlu, İrfan Küçük and Süleyman Baş
Medicina 2025, 61(7), 1147; https://doi.org/10.3390/medicina61071147 - 25 Jun 2025
Viewed by 323
Abstract
Background and Objectives: Fetuin-A is mostly synthesized in the liver. It is a hepatokine, which is an extracellular inhibitor of growth factors. There is a scarcity of data on the clinical utility of serum fetuin-A (SFA) in alcohol-associated cirrhosis (AC). We first [...] Read more.
Background and Objectives: Fetuin-A is mostly synthesized in the liver. It is a hepatokine, which is an extracellular inhibitor of growth factors. There is a scarcity of data on the clinical utility of serum fetuin-A (SFA) in alcohol-associated cirrhosis (AC). We first investigated the association between SFA levels and disease phenotypes in alcoholic liver disease (ALD) patients, including alcohol-associated steatotic liver (ASL) and alcohol-associated hepatitis (AH), along with AC patients. Materials and Methods: There were 26 healthy controls and 64 ALD patients in this case–control study. The severity of the disease in the AC patients was evaluated using the Child–Pugh classification (CPC-A, -B, and -C), and the FH and AC patients’ Maddrey’s differential function scores and the Model of End-Stage Liver Disease Sodium (MELD-Na) scores were computed. We measured SFA levels using a human fetuin-A enzyme-linked immunosorbent assay (ELISA) kit. Results: The SFA concentrations were lower in the AC group and higher in the ASL group [670.72 (412.36) mg/L vs. 1484.61 (858.16) mg/L, respectively; p < 0.001]. When compared to patients with ASL, the SFA levels in AC patients were noticeably lower. However, similar SFA levels were observed for the AH group and the healthy controls, as well as for the ASL group and the healthy controls. Within the AC group, the CPC-A subgroup had the highest median SFA values, while the CPC-C subgroup had the lowest median SFA value. Furthermore, the median SFA levels demonstrated significant and inverse correlations with the CPC scores and the MELD-Na scores (rho = −0.671, p < 0.001; rho = −0.742, p < 0.001, respectively). A negative correlation was observed between the SFA levels and the MELD-Na scores in the AH group (ρ = −0.621, p = 0.013). Conclusions: In ALD patients, decreased SFA levels, which exhibit disease severity, might be an auxiliary biomarker for the follow-up of AC patients. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
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13 pages, 566 KB  
Article
Evaluation of Statins Use in Hemodialysis Patients: A Retrospective Analysis of Clinical and Safety Outcomes
by Abdulmalik S. Alotaibi, Mohamed A. Albekery, Ahmed A. Alanazi, Ibrahim S. Alhomoud, Khalid A. Alamer, Mohammad Shawaqfeh, Reem H. Alshammari, Fayez Alhejaili, Muthana Al Sahlawi, Ibrahim Aldossary, Hajar Adel Aljuayl, Mohammad Alkathiri, Shmeylan Alharbi, Abdulkareem Albekairy and Abdulmalik Alkatheri
Pharmaceuticals 2025, 18(6), 911; https://doi.org/10.3390/ph18060911 - 18 Jun 2025
Viewed by 987
Abstract
Background: Lipid metabolism disturbances are common in end-stage renal disease (ESRD) patients on hemodialysis (HD), leading to dyslipidemia, which is characterized by abnormal plasma lipids and lipoproteins. Although large randomized controlled trials have generally not demonstrated a survival benefit associated with statin therapy [...] Read more.
Background: Lipid metabolism disturbances are common in end-stage renal disease (ESRD) patients on hemodialysis (HD), leading to dyslipidemia, which is characterized by abnormal plasma lipids and lipoproteins. Although large randomized controlled trials have generally not demonstrated a survival benefit associated with statin therapy among patients receiving hemodialysis, limited observational studies have reported potential associations with improved clinical outcomes in this population. Methods: This retrospective cohort study investigated the clinical and safety outcomes of statin use in ESRD patients on HD with documented dyslipidemia over a two-year period from 1 January 2018 to 30 December 2019. The primary endpoints evaluated the clinical outcomes of statins by assessing changes in specific lipid parameters, including low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C). The secondary endpoints assessed safety by monitoring liver enzymes and creatine kinase (CK) levels. Results: Among 179 participants, diabetes mellitus was present in 134 patients (74.9%), while 168 patients (93.9%) had hypertension. Cardiovascular events occurred in 95 patients (53.1%). Statin therapy was administered to 146 patients (82.0%), with atorvastatin being the most frequently prescribed statin (69.3%). Modest reductions in LDL-C levels were observed in the rosuvastatin and atorvastatin groups, whereas slight increases were noted in the simvastatin and non-statin groups. None of these within-group changes were statistically significant. In the atorvastatin group, LDL-C decreased slightly from 2.058 to 2.003 mmol/L. The rosuvastatin group experienced a more pronounced LDL-C reduction from 2.607 to 2.113 mmol/L. Conversely, the simvastatin group showed an LDL-C increase from 1.550 to 1.901 mmol/L. Among the non-statin group, LDL-C increased from 2.678 to 2.820 mmol/L. Liver enzyme and CK levels fluctuated slightly but remained within normal ranges. Conclusions: This study evaluated statin therapy in hemodialysis patients with dyslipidemia. Although modest reductions in LDL-C levels were observed in the atorvastatin and rosuvastatin groups, statin therapy did not reduce the incidence of atherosclerotic events in hemodialysis patients with dyslipidemia. Additionally, statin use was not associated with any clinically or statistically significant effects. Full article
(This article belongs to the Special Issue New Development in Pharmacotherapy of Kidney Diseases)
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13 pages, 269 KB  
Article
Evaluation of Perioperative Risk Factors for Infection by Multidrug-Resistant Bacteria in Patients Undergoing Liver Transplantation
by Rafael Ramos Fernández, Alberto Calvo García, Ainhoa Fernández Yunkera, Silvia Ramos Cerro, Ignacio Garutti, Javier Hortal Iglesias, Patricia Muñoz García, Sergio García Ramos, Adoración Elvira Rodríguez, Mercedes Power Esteban, Patricia Duque González and Patricia Piñeiro
J. Pers. Med. 2025, 15(6), 240; https://doi.org/10.3390/jpm15060240 - 10 Jun 2025
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Abstract
Background: Liver transplantation (LT) is a critical intervention for patients with end-stage liver disease. Infections caused by multidrug-resistant bacteria (MDRB) significantly worsen post-transplant outcomes. The main objective of this study was to analyze perioperative risk factors associated with MDRB infections within six months [...] Read more.
Background: Liver transplantation (LT) is a critical intervention for patients with end-stage liver disease. Infections caused by multidrug-resistant bacteria (MDRB) significantly worsen post-transplant outcomes. The main objective of this study was to analyze perioperative risk factors associated with MDRB infections within six months following LT. Methods: A retrospective analysis was conducted on 133 medical records of patients who underwent liver transplantation between October 2018 and May 2022. Data collected included the presence of MDRB colonization and infection, as well as various perioperative variables. These were analyzed to identify potential risk factors for MDRB infection and colonization. Results: Univariate analysis identified several perioperative variables associated with MDRB infection within six months after LT. Multivariate logistic regression revealed that pre-transplant MDRB colonization (OR 5.72, 95% CI 1.7–18.7, p = 0.005) and the requirement for dialysis during postoperative ICU stay (OR 6.42, 95% CI 1.7–23.4, p = 0.009) were independent risk factors for developing MDRB infections. MDRB infection occurred in 9.4% of patients and was not significantly associated with increased mortality (p = 0.126). Conclusions: These findings contribute to a better understanding of the epidemiology and pathophysiology of MDRB infections in the postoperative period of liver transplantation. This knowledge is essential for developing effective prevention and treatment strategies that may improve outcomes in this patient population. Full article
(This article belongs to the Special Issue Advances in Infectious Disease Epidemiology)
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13 pages, 1330 KB  
Article
Trends and Disparities in Liver Transplantation in the United States: A Nationwide Analysis of Demographic, Clinical, and Socioeconomic Factors (2016–2021)
by Vignesh Krishnan Nagesh, Vivek Joseph Varughese, Marina Basta, Emelyn Martinez, Shruthi Badam, Lokaesh Subramani Shobana, Abdifitah Mohamed, Alin J, Simcha Weissman and Adam Atoot
Med. Sci. 2025, 13(2), 66; https://doi.org/10.3390/medsci13020066 - 1 Jun 2025
Viewed by 849
Abstract
Background: Liver transplantation has become the standard of care for patients with end-stage liver disease. Despite advances in surgical techniques, immunosuppression, and perioperative care, disparities in access and outcomes persist across demographic and socioeconomic lines. Objective: To assess trends and disparities in liver [...] Read more.
Background: Liver transplantation has become the standard of care for patients with end-stage liver disease. Despite advances in surgical techniques, immunosuppression, and perioperative care, disparities in access and outcomes persist across demographic and socioeconomic lines. Objective: To assess trends and disparities in liver transplant admissions in the United States from 2016 to 2021, examining demographic patterns, in-hospital mortality, hospital charges, length of stay, and socioeconomic factors. Methods: Using the National Inpatient Sample (NIS) from 2016 to 2021, we identified liver transplant admissions using ICD-10 PCS codes 0FY00Z1 and 0FY00Z2. Demographic characteristics (age, sex, race, insurance status, and income quartile), clinical outcomes, and resource utilization metrics were analyzed. One-way ANOVA and Hensel’s test were used to assess variance and distribution homogeneity, with a significance threshold of p < 0.05. Results: A total of 9677 liver transplant admissions were analyzed. The mean recipient age remained stable (51–52 years), with males comprising ~62% of transplants. White patients constituted the largest group of recipients (~66–68%), followed by Hispanic (~14–17%) and Black patients (~7–10%). The proportion of transplants relative to liver failure admissions remained stable across racial groups, indicating no widening racial gap during the study period. In-hospital mortality post-transplant remained low (2.37–3.52%) and did not differ significantly by race (p = 0.23), sex (p = 0.24), or income quartile (p = 0.13). Similarly, Charlson Comorbidity Index > 5 did not predict inpatient mortality (p = 0.154). Hospital charges ranged from $578,000 to $766,000, with an average stay of ~21 days. Conclusions: Liver transplantation outcomes, including in-hospital mortality, appear consistent across demographic and socioeconomic groups once patients are admitted for transplant. However, broader disparities in access persist, necessitating further research into pre-transplant barriers and long-term outcomes. These findings support the need for equitable healthcare strategies aimed at optimizing transplant candidacy and survival across all populations. Full article
(This article belongs to the Section Hepatic and Gastroenterology Diseases)
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