Prediction of survival for patients with fulminant hepatic failure

Neuberger, James

doi:10.1002/hep.20562

Cited by 27 publications

(23 citation statements)

References 26 publications

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“…A variety of prognostic variables of ALF have been described, including age, creatinine, bilirubin, phosphate, international normalized ratio, encephalopathy, alpha-fetoprotein, arterial pH, and lactate levels. 21,22,29 Several of these markers merely reflect the loss of liver function, and their discriminatory power increases while the disease progresses and the general condition of the patient deteriorates. Because the decision for liver transplantation .…”

Section: Discussionmentioning

confidence: 99%

Caspase activation is associated with spontaneous recovery from acute liver failure

et al. 2008

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Acute liver failure (ALF) has various causes and is characterized by rapid hepatocyte dysfunction with development of encephalopathy in the absence of preexisting liver disease. Whereas most patients require liver transplantation to prevent the high mortality, some patients recover spontaneously and show complete liver regeneration. Because of the low incidence of ALF, however, the molecular mechanisms of liver dysfunction and regeneration are largely unknown. In this study, we investigated the role of apoptosis and caspases in 70 ALF patients using novel biomarkers that allow the detection of caspase activation in serum samples. Compared with healthy individuals, activation of caspases was strongly enhanced in ALF patients. Interestingly, patients with spontaneous recovery from ALF revealed a significantly higher activation of caspases than patients that required transplantation or died, although in the latter patients extensive DNA fragmentation and signs of nonapoptotic cell death were observed. In the spontaneous survivors, increased caspase activation was accompanied by elevated levels of tumor necrosis factor alpha (TNF-␣) and interleukin-6 (IL-6), important cytokines involved in liver regeneration. Conclusion: Our data suggest that caspase activation and apoptosis are involved in ALF of patients with spontaneous recovery, whereas caspase-independent cell death might be more relevant in irreversible forms of liver failure. These findings might be important for therapeutic options of ALF but also suggest that measurement of caspase activation might be of prognostic value to predict the outcome of acute liver failure. (HEPATOLOGY 2008;47:1624-1633

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Section: Discussionmentioning

confidence: 99%

Caspase activation is associated with spontaneous recovery from acute liver failure

et al. 2008

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“…Currently, patients with acute liver failure are assigned a high priority of UNOS status 1, regardless of MELD score, with ranking within this category dependent upon waiting time on the transplantation list. Several criteria for liver transplantation in ALF have been proposed, but their accuracy and feasibility are controversial [13][14][15][16][17].…”

Section: Meld Score For Liver Transplantationmentioning

confidence: 99%

Accuracy of MELD Scores in Predicting Mortality in Decompensated Cirrhosis from Variceal Bleeding, Hepatorenal Syndrome, Alcoholic Hepatitis, or Acute Liver Failure As Well As Mortality After Non-transplant Surgery or TIPS

Sibae

Cappell

2010

Dig Dis Sci

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“…The prognosis for ALF is very poor, and the syndrome is usually associated with a high mortality of up to 80% (Bernal et al, 2010). There is a definite need for the development of new and effective therapeutic strategies for the treatment of this syndrome (Mas and Rodes, 1997;Neuberger, 2005).…”

Section: Introductionmentioning

confidence: 99%

Protective Role of Cannabinoid Receptor 2 Activation in Galactosamine/Lipopolysaccharide-Induced Acute Liver Failure through Regulation of Macrophage Polarization and MicroRNAs

Tomar¹,

Zumbrun²,

Nagarkatti³

2015

J Pharmacol Exp Ther

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Acute liver failure (ALF) is a potentially life-threatening disorder without any effective treatment strategies. D-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced ALF is a widely used animal model to identify novel hepato-protective agents. In the present study, we investigated the potential of a cannabinoid receptor 2 (CB2) agonist, JWH-133 [(6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo [b,d] pyran], in the amelioration of GalN/LPS-induced ALF. JWH-133 treatment protected the mice from ALF-associated mortality, mitigated alanine transaminase and proinflammatory cytokines, suppressed histopathological and apoptotic liver damage, and reduced liver infiltration of mononuclear cells (MNCs). Furthermore, JWH-133 pretreatment of M1/M2-polarized macrophages significantly increased the secretion of anti-inflammatory cytokine interleukin-10 (IL-10) in M1 macrophages and potentiated the expression of M2 markers in M2-polarized macrophages. In vivo, JWH-133 treatment also suppressed ALF-triggered expression of M1 markers in liver MNCs, while increasing the expression of M2 markers such as Arg1 and IL-10. microRNA (miR) microarray analysis revealed that JWH-133 treatment altered the expression of only a few miRs in the liver MNCs. Gene ontology analysis of the targets of miRs suggested that Toll-like receptor (TLR) signaling was among the most significantly targeted cellular pathways. Among the altered miRs, miR-145 was found to be the most significantly decreased. This finding correlated with concurrent upregulated expression of its predicted target gene, interleukin-1 receptor-associated kinase 3, a negative regulator of TLR4 signaling. Together, these data are the first to demonstrate that CB2 activation attenuates GalN/LPS-induced ALF by inducing an M1 to M2 shift in macrophages and by regulating the expression of unique miRs that target key molecules involved in the TLR4 pathway.

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Prediction of survival for patients with fulminant hepatic failure

Cited by 27 publications

References 26 publications

Caspase activation is associated with spontaneous recovery from acute liver failure

Caspase activation is associated with spontaneous recovery from acute liver failure

Accuracy of MELD Scores in Predicting Mortality in Decompensated Cirrhosis from Variceal Bleeding, Hepatorenal Syndrome, Alcoholic Hepatitis, or Acute Liver Failure As Well As Mortality After Non-transplant Surgery or TIPS

Protective Role of Cannabinoid Receptor 2 Activation in Galactosamine/Lipopolysaccharide-Induced Acute Liver Failure through Regulation of Macrophage Polarization and MicroRNAs

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