Repair macrophages in acute liver failure

Puengel, Tobias; Tacke, Frank

doi:10.1136/gutjnl-2017-314245

Cited by 14 publications

(9 citation statements)

References 12 publications

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“…D-gal can cause liver cell necrosis and lead to ALF, as well as abnormally elevated serum TNF-α, which then triggers the cascade of inflammatory mediators and is closely related to the pathophysiology of ALF[ 28 , 29 ]. In our study, a strong inflammatory response was observed, as evidenced by markedly increased levels of TNF-α, IL-1β, IL-6, and endotoxin, all of which were positively correlated with the dose of D-gal.…”

Section: Discussionmentioning

confidence: 99%

Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

Feng

Cai

et al. 2017

WJG

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AIMTo establish a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure having an appropriate treatment window.METHODSSixteen cynomolgus monkeys were randomly divided into four groups (A, B, C and D) after intracranial pressure (ICP) sensor implantation. D-galactosamine at 0.3, 0.25, 0.20 + 0.05 (24 h interval), and 0.20 g/kg body weight, respectively, was injected via the small saphenous vein. Vital signs, ICP, biochemical indices, and inflammatory factors were recorded at 0, 12, 24, 36, 48, 72, 96, and 120 h after D-galactosamine administration. Progression of clinical manifestations, survival times, and results of H&E staining, TUNEL, and Masson staining were recorded.RESULTSCynomolgus monkeys developed different degrees of debilitation, loss of appetite, and jaundice after D-galactosamine administration. Survival times of groups A, B, and C were 56 ± 8.7 h, 95 ± 5.5 h, and 99 ± 2.2 h, respectively, and in group D all monkeys survived the 144-h observation period except for one, which died at 136 h. Blood levels of ALT, AST, CK, LDH, TBiL, Cr, BUN, and ammonia, prothrombin time, ICP, endotoxin, and inflammatory markers [(tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6)] significantly increased compared with baseline values in different groups (P < 0.05). Pathological results showed obvious liver cell necrosis that was positively correlated with the dose of D-galactosamine.CONCLUSIONWe successfully established a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure, and the single or divided dosage of 0.25 g/kg is optimal for creating this model.

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Section: Discussionmentioning

confidence: 99%

Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

Feng

Cai

et al. 2017

WJG

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“…In this regard, MER receptor tyrosine kinase (MERTK) is expressed by monocytes and macrophages that have features of restorative phagocytes. (152) Although these MERTK + macrophages seem to be associated with disease severity in acute-on-chronic liver failure, (153) they apparently indicate proper resolution from acute liver failure in patients. (154)…”

Section: Prognostic Value Of Macrophage-related Markers In Human Livementioning

confidence: 99%

Liver Macrophages: Old Dogmas and New Insights

2019

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Inflammation is a hallmark of virtually all liver diseases, such as liver cancer, fibrosis, nonalcoholic steatohepatitis, alcoholic liver disease, and cholangiopathies. Liver macrophages have been thoroughly studied in human disease and mouse models, unravelling that the hepatic mononuclear phagocyte system is more versatile and complex than previously believed. Liver macrophages mainly consist of liver-resident phagocytes, or Kupffer cells (KCs), and bone marrow-derived recruited monocytes. Although both cell populations in the liver demonstrate principal functions of macrophages, such as phagocytosis, danger signal recognition, cytokine release, antigen processing, and the ability to orchestrate immune responses, KCs and recruited monocytes retain characteristic ontogeny markers and remain remarkably distinct on several functional aspects. While KCs dominate the hepatic macrophage pool in homeostasis ("sentinel function"), monocyte-derived macrophages prevail in acute or chronic injury ("emergency response team"), making them an interesting target for novel therapeutic approaches in liver disease. In addition, recent data acquired by unbiased large-scale techniques, such as single-cell RNA sequencing, unraveled a previously unrecognized complexity of human and murine macrophage polarization abilities, far beyond the old dogma of inflammatory (M1) and anti-inflammatory (M2) macrophages. Despite tremendous progress, numerous challenges remain in deciphering the full spectrum of macrophage activation and its implication in either promoting liver disease progression or repairing injured liver tissue. Being aware of such heterogeneity in cell origin and function is of crucial importance when studying liver diseases, developing novel therapeutic interventions, defining macrophage-based prognostic biomarkers, or designing clinical trials. Growing knowledge in gene expression modulation and emerging technologies in drug delivery may soon allow shaping macrophage populations toward orchestrating beneficial rather than detrimental inflammatory responses. (Hepatology Communications 2019;3:730-743). T he liver is the largest solid organ and exerts vital metabolic functions. Liver diseases leading to liver cirrhosis or cancer are increasingly challenging for public health, the current trend being an augmentation of such diseases mainly caused by changes in alimentation and life habits. (1) Liver diseases are various by nature in terms of etiologies, chronicity, and chances of recovery. However, one constant feature is the presence of liver inflammation, and most remarkably, there is an apparent compulsory association of inflammation with a poor outcome for patients. (2-6) Liver macrophages are included in the mononuclear phagocyte system and are renown cornerstones in most if not all inflammation-related liver disorders due to their ability to respond to a seemingly infinite

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“…GC can inhibit the function of cytotoxic T lymphocytes (CTL) and intercellular adhesion molecule-1 (ICAM-1), thereby preventing or delaying excessive cellular immunity and alleviating liver cell injury (26,27). This treatment also suppresses the release of inflammatory mediators from intrahepatic and extrahepatic mononuclear phagocytes, preventing or delaying secondary hepatic microcirculation disorder (28)(29)(30). In addition, GCs can inhibit TNF-related apoptosis-inducing ligand (TRAIL) mediated apoptosis of hepatocytes by up-regulating P-glycoprotein (P-gp) expression (31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and predictive factors of glucocorticoid therapy for patients with hepatitis B virus-related acute-on-chronic liver failure

Shi¹,

Zhu²,

Liang³

et al. 2022

AGEB

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Background and study aims: Glucocorticoid (GC) treatment for liver failure is controversial. This study sought to evaluate the efficacy and predictive factors of glucocorticoid therapy for hepatitis B virus-related acute-on-chronic liver failure (HBV- ACLF). Patients and methods: A total of 302 patients with HBV- ACLF were enrolled and categorized by treatment modality (GC vs. Control). Baseline characteristics, liver function, disease complications, and mortality were recorded. Univariate and multivariate analysis were used to identify predictive factors for HBV-ACLF-related mortality. Results: GC therapy significantly improved the 30- and 60-day mortality of HBV-ACLF patients (4.64% vs. 11.92%, P=0.022 and 16.56% vs. 25.83%, P=0.049 for the Control and GC groups, respectively) and GC was an independent prognostic factor for 30-day mortality (OR = 0.177, 95% CI 0.051-0.616, P = 0.007). However, enhanced survival was not associated with improved liver function. There were no significant differences in the incidence of complications (i.e., ascites, bacterial infection, encephalopathy, hepatorenal syndrome, and gastrointestinal bleeding) between the GC and Control groups (P >0.05), except that fungal infection occurred with higher frequency in the GC group (P = 0.037). A significant improvement in the 30-day survival associated with GC therapy was observed among patients <40 years of age, a Model for End-stage Liver Disease (MELD) score of 25-35 or a CLIF- Consortium ACLF (CLIF-C ACLF) grade 0-1 (all P <0.05). Conclusions: GC therapy improved the short-term (30- and 60- day) mortality of patients with HBV-ACLF. This treatment may be of particular benefit to patients who are <40 years of age, have a MELD score of 25-35, or have a CLIF-C ACLF grade of 0-1. (Acta gastroenterol. belg., 2022, 85, 593-600).

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Repair macrophages in acute liver failure

Cited by 14 publications

References 12 publications

Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

Liver Macrophages: Old Dogmas and New Insights

Efficacy and predictive factors of glucocorticoid therapy for patients with hepatitis B virus-related acute-on-chronic liver failure

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