Recent advances in management of acute liver failure

Panackel, Charles; Thomas, Richard K.; Sebastian, Benoy; Mathai, Sunil

doi:10.4103/0972-5229.148636

Cited by 27 publications

(14 citation statements)

References 47 publications

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“…TTP typically involves the brain and kidneys, but TTP-like syndrome prominently develops in one or more of vital organs [ 11 – 14 ], including the liver [ 15 , 16 ], heart [ 17 , 18 ], lungs [ 11 – 13 , 19 , 20 ], pancreas [ 21 ] and others with or without involvement of the brain and kidneys. Oftentimes fewer schistocytes are present on the blood film and intravascular hemolysis could have easily missed [ 11 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

TTP-like syndrome: novel concept and molecular pathogenesis of endotheliopathy-associated vascular microthrombotic disease

Chang

2018

Thrombosis J

145

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TTP is characterized by microangiopathic hemolytic anemia and thrombocytopenia associated with brain and kidney dysfunction. It occurs due to ADAMTS13 deficiency. TTP-like syndrome occurs in critically ill patients with the similar hematologic changes and additional organ dysfunction syndromes. Vascular microthrombotic disease (VMTD) includes both TTP and TTP-like syndrome because their underlying pathology is the same disseminated intravascular microthrombosis (DIT). Microthrombi are composed of platelet-unusually large von Willebrand factor multimers (ULVWF) complexes. TTP occurs as a result of accumulation of circulating ULVWF secondary to ADAMTS13 deficiency. This protease deficiency triggers microthrombogenesis, leading to “microthrombi” formation in microcirculation. Unlike TTP, TTP-like syndrome occurs in critical illnesses due to complement activation. Terminal C5b-9 complex causes channel formation to endothelial membrane, leading to endotheliopathy, which activates two different molecular pathways (i.e., inflammatory and microthrombotic). Activation of inflammatory pathway triggers inflammation. Activation of microthrombotic pathway promotes platelet activation and excessive endothelial exocytosis of ULVWF from endothelial cells (ECs). Overexpressed and uncleaved ULVWF become anchored to ECs as long elongated strings to recruit activated platelets, and assemble “microthrombi”. In TTP, circulating microthrombi typically be lodged in microvasculature of the brain and kidney, but in TTP-like syndrome, microthrombi anchored to ECs of organs such as the lungs and liver as well as the brain and kidneys, leading to multiorgan dysfunction syndrome. TTP occurs as hereditary or autoimmune disease and is the phenotype of ADAMTS13 deficiency-associated VMTD. But TTP-like syndrome is hemostatic disorder occurring in critical illnesses and is the phenotype of endotheliopathy-associated VMTD. Thus, this author’s contention is TTP and TTP-like syndrome are two distinctly different disorders with dissimilar underlying pathology and pathogenesis.

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Section: Introductionmentioning

confidence: 99%

TTP-like syndrome: novel concept and molecular pathogenesis of endotheliopathy-associated vascular microthrombotic disease

Chang

2018

Thrombosis J

145

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“…Acute liver failure (ALF) is a serious condition resulting from the development of hepatocellular dysfunction over a period of several days or a few weeks (1). ALF is very harmful to patient health, and has a mortality rate of 80% (2).…”

Section: Introductionmentioning

confidence: 99%

Lipoxin A4 exerts protective effects against experimental acute liver failure by inhibiting the NF-κB pathway

Jiang

Jiang³

et al. 2016

International Journal of Molecular Medicine

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Abstract.Although rare, acute liver failure (ALF) is associated with high levels of mortality, warranting the development of novel therapies. Nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) play roles in ALF. Lipoxin A4 (LXA4) has been shown to alleviate inflammation in non-hepatic tissues. In the present study, we explored whether LXA4 exerted hepatoprotective effects in a rat model of ALF. A rat model of ALF was generated by intraperitoneal injections of D-galactosamine (300 mg/kg) and lipopolysaccharide (50 µg/kg). Animals were randomly assigned to: control group (no ALF); model group (ALF); and the groups treated with a low dose (0.5 µg/kg), medium dose (1 µg/kg), and high dose (2 µg/kg) of LXA4 (all with ALF); and pyrrolidine dithiocarbamate (PDTC)-treated group (ALF and 100 mg/kg PDTC, an inhibitor of NF-κB). Liver histology was measured using H&E staining, serum levels by ELISA, and liver mRNA expression was measured by RT-PCR for the detection of the pro-inflammatory cytokines TNF-α and IL-6. Liver cell apoptosis (as measured using the TUNEL method and examining caspase-3 activity), and Kupffer cell NF-κB activity [using an electrophoretic mobility shift assay (EMSA)] were examined. Serum levels of transaminases, TNF-α and interleukin-6 (IL-6) were substantially higher in the model group compared to controls. In the model group, significant increases in TNF-α and IL-6 mRNA expression, TUNEL-positive cells, and caspase-3 activity in the liver tissue were noted. LXA4 improved liver pathology and significantly decreased the indicators of inflammatory response and apoptosis in a dose-dependent manner. High-dose LXA4 provided better protection than PDTC. LXA4 administration significantly decreased NF-κB expression in hepatocytes and Kupffer cells. These results indicated that LXA4 inhibited NF-κB activation, reduced the secretion of pro-inflammatory cytokines, and inhibited apoptosis of liver cells, thereby exerting protective effects against ALF.

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“…In this context, severe acute liver failure (ALF) represents a life-threatening condition. The rapid dysfunctional course of a previously normal liver is responsible for a high mortality rate [1].…”

Section: Introductionmentioning

confidence: 99%

Action of Melatonin on Severe Acute Liver Failure in Rats

Salvi¹,

Schemitt²,

Colares³

et al. 2017

IOSRJPBS

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Abstract:Severe acute liver failure (ALF) manifests itself as a rare syndrome, with multiple etiologies for similar clinical conditions. Melatonin (MLT) is a lipophilic indolamine that is synthesized in the pineal gland from serotonin. This study was designed to evaluate hepatic changes resulting from the thioacetamide-induced ALF model, as well as the effects of MLT treatment in male Wistar rats (n = 56) in 24-and 48-h experiments. The results indicate a hepatoprotective effect of MLT, with no difference between the studied times, and increased animal survival.

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Recent advances in management of acute liver failure

Cited by 27 publications

References 47 publications

TTP-like syndrome: novel concept and molecular pathogenesis of endotheliopathy-associated vascular microthrombotic disease

TTP-like syndrome: novel concept and molecular pathogenesis of endotheliopathy-associated vascular microthrombotic disease

Lipoxin A4 exerts protective effects against experimental acute liver failure by inhibiting the NF-κB pathway

Action of Melatonin on Severe Acute Liver Failure in Rats

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