Liver dysfunction and various hepatic disorders cause neuropsychiatric abnormalities including depression, anxiety, cognitive impairment and personality changes through liver-brain axis imbalance, greatly worsening patient prognosis. The liver-brain axis acts as a bidirectional network via neural, humoral, immune and gut microbiota pathways, and its disruption dominates liver disease-related central nervous system (CNS) injury. Toxic metabolites such as bilirubin activate the transient receptor potential cation channel subfamily M member 2 (TRPM2)-spleen tyrosine kinase (SYK)-nuclear factor kappa-B (NF-κB) pathway in microglia, triggering excessive glutamatergic synapse phagocytosis in the anterior cingulate cortex (ACC) and sustained neuroinflammation with irreversible neural circuit damage. This review summarizes the pathogenesis of neuropsychiatric complications induced by liver dysfunction and liver transplantation, focusing on blood-brain barrier (BBB) disruption, systemic immune activation, neurotransmitter imbalance and resident immune cell phenotypic shifts. It clarifies four liver-brain axis regulatory pathways, highlights microglial central functions, and addresses gut-liver-brain axis crosstalk, meningeal immunity, choroid plexus barrier damage and circadian rhythm disturbance. It also concludes diagnostic biomarkers including bilirubin and fibroblast growth factor 21 (FGF21), alongside therapeutic targets covering the TRPM2-SYK-NF-κB pathway, microglial polarization and gut microbiota. This study provides a unified theoretical framework for clinical diagnosis, risk stratification and targeted treatment of liver disease-related neuropsychiatric complications, and explains CNS dysfunction mechanisms underlying metabolic dysfunction-associated steatotic liver disease (MASLD), liver cirrhosis and acute-on-chronic liver failure.

Acetaminophen (APAP) overdose can induce hepatic injury and even acute liver failure. Astragaloside IV (AS-IV), a saponin isolated from Astragalus membranaceus, demonstrates protective effects on both digestive and immune systems owing to its antioxidant and anti-inflammatory properties. This study aims to investigate the protective effects and underlying mechanisms of AS-IV against APAP-induced liver injury (AILI) in mice. Potential therapeutic targets of AS-IV against AILI were predicted through network pharmacology and GEO data mining. Functional enrichment analysis was performed on the identified targets. Molecular docking and dynamics simulations were conducted to validate the binding interactions between AS-IV and core targets within the PPAR signaling pathway. For in vivo validation, fifty C57BL/6 mice were randomly allocated into five groups: control, APAP model, AS-IV low-dose, AS-IV high-dose, and N-acetylcysteine treatment groups. Following model establishment, serum AST and ALT levels were measured to assess liver function. Hepatic histopathological changes were evaluated by HE staining, while RT-qPCR and WB were employed to quantify the expression of key genes and proteins. Network pharmacology analysis identified 43 potential therapeutic targets of AS-IV against AILI, including key molecules such as IL1B, PPARG, RXRA, and FOS. KEGG pathway enrichment revealed significant associations with the PPAR signaling pathway, measles, and non-alcoholic fatty liver disease. In vivo experiments demonstrated that AS-IV treatment effectively attenuated histopathological liver damage in AILI mice, as evidenced by significantly reduced serum ALT and AST levels. Furthermore, AS-IV administration markedly upregulated both mRNA and protein expression levels of critical metabolic regulators PCK1, RXRA, and PPARG. In conclusion, AS-IV alleviates AILI by modulating the PPAR signaling pathway through regulation of PCK1, PPARG, and RXRA.

Hyperlactatemia is a frequent finding in critically ill patients and is traditionally interpreted as a marker of tissue hypoxia and anaerobic metabolism. However, in sepsis, septic shock, and other states of circulatory failure - including post-cardiac arrest syndrome - elevated lactate concentrations often occur despite preserved arterial oxygenation and adequate oxygen delivery. Increasing evidence indicates that lactate is a central metabolic intermediate whose circulating concentration reflects the balance between stress-induced production, cellular utilization, and organ clearance. While hepatic metabolism has long been considered the dominant pathway for lactate disposal, the kidneys - particularly proximal tubular cells - play a major and often underappreciated role in lactate utilization and clearance. Acute kidney injury (AKI), a common complication of sepsis, directly alters systemic lactate homeostasis. In this narrative review, we synthesize current knowledge on lactate biology in critical illness and examine the contribution of renal metabolism to hyperlactatemia in patients with sepsis-induced AKI. We propose that lactate should be interpreted as an integrated metabolic signal reflecting systemic stress and impaired clearance - rather than as a surrogate for hypoxia alone - with important implications for the management of septic AKI. The potential of urinary lactate as a marker of proximal tubular metabolic dysfunction and the emerging role of protein lactylation in modulating the inflammatory-to-reparative phenotypic transition are also discussed.

Since 2012, 2 viral causes of hepatitis have been identified in horses. Much remains to be discovered about their transmission, risk factors for clinical disease, diagnosis, and treatment approaches. Equine parvovirus-hepatitis has been identified as the cause of acute hepatic necrosis, previously known as Theiler's disease. Equine hepacivirus is recognized as a cause of chronic fibrosing hepatitis. Diagnosis relies on ruling out other causes of hepatitis and documenting infection by serum or liver polymerase chain reaction. There is no direct antiviral for either condition and treatments are symptomatic or aimed at ameliorating effects of liver failure and encephalopathy if present.

A baseline MAP <80 mmHg is an independent predictor of short- and mid-term mortality in patients with AH. Strategies aimed at restoring hemodynamic stability may improve outcomes in this high-risk population.

Acute liver failure (ALF) has been described at initial presentation of citrullinemia type 1 (CTLN1), but recurrent hepatic decompensations during medical treatment have not been reported. We describe 5 children developing ALF episodes, including one who required emergency liver transplantation. Our findings expand the CTLN1 phenotype and support early liver transplant referral in selected cases.

Sepsis is a life-threatening disorder triggered by an unregulated host reaction to infection, and it represents a worldwide health dilemma given the scarcity of effective treatment strategies. Sepsis usually leads to lethal multiorgan dysfunctions, including acute liver failure (ALF) and acute lung injury (ALI). Recent studies have found that altered programmed cell death (PCD) processes, including apoptosis, autophagy, ferroptosis, and pyroptosis, belong to key mechanisms that trigger sepsis-associated multiorgan disorders. Among them, ferroptosis is a unique mode of PCD characterized by the accumulation of iron-dependent reactive oxygen species (ROS) and lipid peroxidation. Mediating ferroptosis is a promising strategy against sepsis. Recently, studies have identified multiple natural products for treating sepsis-associated lung and liver injuries by targeting ferroptosis. Here, we provide an overview of the mechanisms and potential therapeutic targets underlying ferroptosis in sepsis. The natural products with ferroptosis targeting will be summarized. Notably, most current evidence supporting the therapeutic potential of natural products is derived from preclinical investigations, and high-quality clinical data remain scarce, requiring further validation for clinical translation. We hope this study provides new perspectives for the future treatment of sepsis-induced ALI and ALF.