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Unlabelled: Acute liver failure remains a critical clinical condition, with high mortality rates, and increased apoptosis of hepatocytes represents a key event in the cause of liver failure. Alpha-1-antitrypsin (AAT) is synthesized and secreted mainly by hepatocytes, and plasma purified AAT is used for augmentation therapy in patients with AAT deficiency. Because AAT therapy exerts antiinflammatory and immune modulatory activities in various experimental models, and it was recently suggested that AAT exerts antiapoptotic activities, we aimed to explore whether administration of AAT may represent a therapeutic strategy to treat acute liver failure in mice. Well-established preclinical models of acute liver failure such as the Jo2 FAS/CD95 activating model and models of acetaminophen and α-amanitin poisoning were used. Therapeutic effects of AAT were evaluated by monitoring animal survival, histopathological changes, measurement of caspase activity, and serum cytokine levels. Systemic treatment with AAT significantly decreased Jo2-induced liver cell apoptosis and prolonged survival of mice. Native and oxidized (lacking elastase inhibitory activity) forms of AAT were equally effective in preventing acute liver injury and showed direct inhibition of active caspase-3 and -8 in liver homogenates and in a cell-free system in vitro. Concomitantly, mice treated with AAT showed significantly lower serum levels of tumor necrosis factor alpha (TNF-α), which also paralleled the reduced activity of ADAM17 (TACE). Noticeably, the increased survival and a reduction of apoptotic hepatocytes were also observed in the α-amanitin and acetaminophen-induced liver injury mouse models.
Conclusion: Our data suggest that systemic administration of AAT can be a promising therapy to treat acute liver failure and clinical studies to explore this treatment in humans should be initiated.
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http://dx.doi.org/10.1002/hep.27024 | DOI Listing |
Liver Int
January 2025
Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Introduction: Racial/ethnic disparities have been previously reported in renal and hepatic disease care; however, acute kidney injury (AKI) in the setting of cirrhosis (hepatorenal syndrome [HRS]-AKI) despite its complexity requiring a multidisciplinary approach, remains understudied.
Methods: To identify unique associations of clinical and sociodemographic factors with mortality and length of stay (LOS) among patients hospitalised with HRS-AKI, hierarchical regression analysis was conducted, along with a mediation analysis to estimate how race-related differences in in-hospital mortality were influenced by payer type, area household income, and clinical severity.
Results: Black patients demonstrated a significantly higher odds of in-hospital mortality, compared to their white counterparts, adjusting for (1) sex and age, (2) sex, age, payer type, and area household income and (3) sex, age, and clinical severity [OR 1.
Diagn Microbiol Infect Dis
December 2024
Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, China. Electronic address:
Objectives: To evaluate the rationality of the clinical use of ceftazidime-avibactam (CAZ-AVI) for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in a real-world setting.
Methods: We established the rational evaluation criteria based on drug instructions and relevant guidelines to retrospectively evaluate the use of CAZ-AVI to treat CRKP infections from June 2020 to June 2023 in a tertiary hospital in China. Patients were divided into the rational use group and irrational use group.
Int Immunopharmacol
December 2024
Department of Emergency, Kashi Prefecture Second People's Hospital, Uygur Autonomous Region Kashi, Xinjiang, 844000, China; Department of Emergency, Shanghai Tenth People's Hospital, School of Medicine Tongji University, Shanghai 200072, China. Electronic address:
Background: Sepsis represents a critical health crisis often leading to the failure of multiple organs, with the liver playing a pivotal role in controlling inflammation and defending against systemic infections. The exacerbation of liver damage can escalate sepsis severity, underscoring the necessity to delve into the molecular mechanisms underlying sepsis-induced acute liver injury (ALI). The role of alternative splicing (AS), a complex post-transcriptional mechanism, has been occasionally noted in relation to sepsis across different investigations.
View Article and Find Full Text PDFEur Heart J Cardiovasc Pharmacother
December 2024
Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Vorarlberg, Austria.
Objectives: This review aims to examine the evidence on the benefits and risks of lipid lowering drugs in patients with liver disease. Elevated liver enzyme levels often lead to cautious discontinuation of these drugs, potentially withholding from patients their benefit in reducing cardiovascular disease morbidity and mortality.
Methods And Results: Using a literature search of PubMed, we examine the efficacy and safety profiles of various lipid lowering agents, including statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, fibrates, and icosapent ethyl, focusing particularly on their potential side effects related to liver health.
Am J Trop Med Hyg
December 2024
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Dengue infection poses a significant public health challenge in tropical countries. In Thailand, children ages 5-14 years are among the groups with the highest incidence of dengue. This study aimed to determine the prevalence of gastrointestinal (GI) manifestations in children with dengue infection and assess prognostic factors for severe dengue.
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