• ACLF
• CIBERSORT
• WGCNA
• biomarker genes
• neutrophil

• Humans
• Acute-On-Chronic Liver Failure/genetics
• Acute-On-Chronic Liver Failure/diagnosis
• Acute-On-Chronic Liver Failure/blood
• Acute-On-Chronic Liver Failure/immunology
• Neutrophils/immunology
• Neutrophils/metabolism
• Biomarkers/blood
• Matrix Metalloproteinase 9/genetics
• Matrix Metalloproteinase 9/blood
• Male
• Gene Expression Profiling
• Chemokine CCL5/genetics
• Female
• Middle Aged
• Adult
• Gene Regulatory Networks

• chemokines
• chronic liver failure
• cytokines
• immune response
• immunosuppression
• innate and adaptive immune response
• liver cirrhosis

• Humans
• Immunity, Innate
• Liver Failure/immunology
• Animals
• Immune System/metabolism
• Immune System/immunology
• Adaptive Immunity
• Killer Cells, Natural/immunology
• Cytokines/metabolism
• Liver/immunology
• Liver/metabolism
• Liver/pathology

• SKN No. 148 wroclaw medical university
• SUBZ.D260.24.076 wroclaw medical university

• ALD
• G protein coupled receptors
• HCC
• NAFLD
• Poly-unsaturated fatty acid lipid mediators
• eicosanoids
• liver cancer
• liver fibrosis
• lyso-phospholipids
• steatohepatitis
• viral hepatitis

• Humans
• Non-alcoholic Fatty Liver Disease/complications
• Liver Diseases, Alcoholic/metabolism
• Carcinoma, Hepatocellular/pathology
• Phospholipids/metabolism
• Liver Neoplasms/pathology
• Liver/pathology

• U01 AA026962 NIAAA NIH HHS
• R21 AA029206 NIAAA NIH HHS

• Acute-on-chronic liver failure
• Chronic viral hepatitis B
• Monocyte-lymphocyte ratio
• Neutrophil-lymphocyte ratio
• Prognosis

• BCG vaccine
• biomarker
• innate immunity
• monocyte
• tuberculosis

Lipids are organic compounds insoluble in water with a variety of metabolic and non-metabolic functions. They not only represent an efficient energy substrate but can also act as key inflammatory and anti-inflammatory molecules as part of a network of soluble mediators at the interface of metabolism and the immune system. The role of endogenous bioactive lipid mediators has been demonstrated in several inflammatory diseases (rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, cancer). The liver is unique in providing balanced immunotolerance to the exposure of bacterial components from the gut transiting through the portal vein and the lymphatic system. This balance is abruptly deranged in liver failure syndromes such as acute liver failure and acute-on-chronic liver failure. In these syndromes, researchers have recently focused on bioactive lipid mediators by global metabonomic profiling and uncovered the pivotal role of these mediators in the immune dysfunction observed in liver failure syndromes explaining the high occurrence of sepsis and subsequent organ failure. Among endogenous bioactive lipids, the mechanistic actions of three classes (eicosanoids, pro-resolving lipid mediators and lysophospholipids) in the pathophysiological modulation of liver failure syndromes will be the topic of this narrative review. Furthermore, the therapeutic potential of lipid-immune pathways will be described.

• acute liver failure
• acute on chronic liver failure
• cirrhosis
• lipids
• liver
• liver failure
• metabonome
• systems biology

The liver is a multifaceted organ; its location and detoxifying function expose this organ to countless injuries. Acute-on-chronic failure liver (ACLF) is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease. An infection environment, ascites, increased liver enzymes and prothrombin time, encephalopathy and fast-evolving multiorgan failure, leading to death, usually accompany this. The pathophysiology remains poorly understand. In this context, animal models become a very useful tool in this regard, as understanding; the disease may be helpful in developing novel therapeutic methodologies for ACLF. However, although animal models display several similarities to the human condition, they do not represent all ACLF manifestations, resulting in significant challenges. An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-GaIN, potentiating liver damage supports the methodologies applied to induce experimental ACLF. The entire methodology has been described mostly for rats. Nevertheless, a quick PubMed database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models. These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.

• Liver disease
• Acute-on-chronic liver failure
• Cirrhosis
• Acute decompensate event
• Translational study
• Animal models

The liver is a multifaceted organ; its location and detoxifying function expose this organ to countless injuries. Acute-on-chronic failure liver (ACLF) is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease. An infection environment, ascites, increased liver enzymes and prothrombin time, encephalopathy and fast-evolving multiorgan failure, leading to death, usually accompany this. The pathophysiology remains poorly understand. In this context, animal models become a very useful tool in this regard, as understanding; the disease may be helpful in developing novel therapeutic methodologies for ACLF. However, although animal models display several similarities to the human condition, they do not represent all ACLF manifestations, resulting in significant challenges. An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-GaIN, potentiating liver damage supports the methodologies applied to induce experimental ACLF. The entire methodology has been described mostly for rats. Nevertheless, a quick PubMed database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models. These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.

• Liver disease
• Acute-on-chronic liver failure
• Cirrhosis
• Acute decompensate event
• Translational study
• Animal models

Fewer than 50% of patients with acute-on-chronic liver failure (ACLF) recover spontaneously, and ACLF has high mortality without liver transplantation. Oxidative stress has been shown to mediate hepatic inflammation during acute liver failure (ALF). We wanted to see if a biomarker for oxidative stress might be used to measure the severity and prognosis of ACLF patients.

A retrospective cohort of 124 ACLF patients, as well as healthy individuals, liver cirrhosis and ALF patients, was studied between January 2015 and September 2018. The levels of plasma superoxide dismutase (SOD) were detected using an ELISA commercial kit, and the Kaplan–Meier method was used for survival analysis.

Patients with ACLF had statistically higher plasma SOD levels than the controls did (healthy controls and liver cirrhosis patients); however, the levels did not differ from those in patients with ALF. The plasma SOD level may be an inexpensive, easily accessible, and significant independent prognostic index for mortality on multivariate analysis (HR = 1.201, 95% CI 1.001–1.403, P < 0.01) as well as the model for end-stage liver disease (MELD) score. A level of SOD > 428 U/mL was linked to a statistically significant increase in the likelihood of death or liver transplantation in ACLF patients. Combination of plasma SOD levels and MELD scores improved performance in measuring the severity and prognosis of ACLF patients.

Patients with ACLF can be classified into high-risk and low-risk groups based on their plasma SOD levels at the time of admission to the hospital. The patient outcome is more closely connected with the combination of SOD level and MELD score than either value alone. This approach might be used to predict patient prognoses and prioritize liver transplant candidates.

• acute-on-chronic liver failure
• cirrhosis
• immunopathology
• liver transplantation
• stem cell therapy

• ACLF
• HBV
• Mortality
• ROS
• suPAR

Rhubarb, as a traditional Chinese medicine, is the preferred drug for the treatment of stagnation and constipation in clinical practice. It has been reported that rhubarb possesses hepatotoxicity, but its mechanism in vivo is still unclear.

In this study, the chemical components in rhubarb were identified based on UPLC-Q-TOF/MS combined with data postprocessing technology. The metabolic biomarkers obtained through metabolomics technology were related to rhubarb-induced hepatotoxicity. Furthermore, the potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology involving the above components and metabolites. Meanwhile, GO gene enrichment analysis and KEGG pathway analysis were performed on the common targets.

Twenty-eight components in rhubarb were identified based on UPLC-Q-TOF/MS, and 242 targets related to rhubarb ingredients were predicted. Nine metabolic biomarkers obtained through metabolomics technology were closely related to rhubarb-induced hepatotoxicity, and 282 targets of metabolites were predicted. Among them, the levels of 4 metabolites, namely dynorphin B (10–13), cervonoyl ethanolamide, lysoPE (18:2), and 3-hydroxyphenyl 2-hydroxybenzoate, significantly increased, while the levels of 5 metabolites, namely dopamine, biopterin, choline, coenzyme Q9 and P1, P4-bis (5ʹ-uridyl) tetraphosphate significantly decreased. In addition, 166 potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology. The KEGG pathway analysis was performed on the common targets to obtain 46 associated signaling pathways.

These data suggested that rhubarb may cause liver toxicity due to its action on dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), phosphodiesterase 4B (PDE4B), vanilloid receptor (TRPV1); transient receptor potential cation channel subfamily M member 8 (TRPM8), prostanoid EP2 receptor (PTGER2), acetylcholinesterase (ACHE), muscarinic acetylcholine receptor M3 (CHRM3) through the cAMP signaling pathway, cholinergic synapses, and inflammatory mediators to regulate TRP channels. Metabolomics technology and network pharmacology were integrated to explore rhubarb hepatotoxicity to promote the reasonable clinical application of rhubarb.

• hepatotoxicity
• metabolomics
• network pharmacology
• rhubarb