Fulminant Hepatic Failure in Children

Farmer, Douglas G.; Venick, Robert S.; McDiarmid, Sue V.; Duffy, John P.; Kattan, Omar; Hong, Johnny C.; Vargas, Jorge; Yersiz, Hasan; Busuttil, Ronald W.

doi:10.1097/sla.0b013e3181b480ad

Cited by 54 publications

(20 citation statements)

References 31 publications

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“…Orthotopic liver transplantation (OLT) is the only effective treatment [1, 2]. However, the shortage of available donor livers and multiple postoperative complications limit widespread clinical application of OLT [3].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells increase expression of heme oxygenase-1 leading to anti-inflammatory activity in treatment of acute liver failure

et al. 2017

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BackgroundMesenchymal stem cells (MSCs) have been studied for the treatment of acute liver failure (ALF) for several years. MSCs may exert their effect via complex paracrine mechanisms. Heme oxygenase (HO) 1, a rate-limiting enzyme in heme metabolism, exerts a wide range of anti-inflammatory, anti-apoptotic and immunoregulatory effects in a variety of diseases. However, the relationship between MSCs and HO-1 in the treatment of ALF is still unclear. We investigated the preventive and therapeutic potential of intravenously administered BMSCs.MethodsBone marrow-derived mesenchymal stem cells (BMSCs) obtained from Sprague–Dawley rats were isolated and cultured. We employed BMSCs, hemin (a HO-1 inducer) and zinc protoporphyrin (ZnPP, the HO-1 activity inhibitor) in D-galactosamine (D-Gal)/lipopolysaccharides (LPS)-induced ALF rats. Rats were sacrificed at days 1, 3, 5, and 7 post-transfusion, respectively. Blood samples and liver tissues were collected. Hepatic injury, HO-1 activity, chemokines, inflammatory cytokines, the number and oxidative activity of neutrophils, ki67, and TUNEL-positive cells were evaluated.ResultsHO-1 induction or BMSCs transplantation attenuated D-galactosamine/lipopolysaccharide-induced increases in alanine aminotransferase, aspartate aminotransferase, total bilirubin (TBIL), ammonia, and inflammatory cytokines. Treatment with hemin or BMSCs also inhibited neutrophil infiltration, oxidative activity, and hepatocyte apoptosis. The protective effect of BMSCs was partially neutralized by ZnPP, suggesting the key role of HO-1 in the process.ConclusionsThese findings may correlate with inhibition of nuclear factor-κ B activation. BMSCs ameliorated ALF by increasing the HO-1 expression, which reduced PMN infiltration and function, and played an important anti-inflammatory and anti-apoptotic role.Graphical AbstractProposed mechanism by which BMSCs reduce inflammation, neutrophil activation, and hepatocyte apoptosis and promote hepatocyte proliferation via HO-1. BMSCs increase HO-1 expression in liver via Nrf2. HO-1 protects against LPS/D-Gal-induced ALF by inhibiting neutrophil infiltration and inflammatory burst, and hepatocyte apoptosis and necrosis. HO-1 also promotes hepatocyte proliferation. Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0524-3) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells increase expression of heme oxygenase-1 leading to anti-inflammatory activity in treatment of acute liver failure

et al. 2017

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“…Orthotopic liver transplantation is the treatment of choice for FHF and end-stage liver disease [1]. However, liver transplantation has limitations, primarily due to a lack of readily available donors.…”

Section: Introductionmentioning

confidence: 99%

Amniotic-Fluid–Derived Mesenchymal Stem Cells Overexpressing Interleukin-1 Receptor Antagonist Improve Fulminant Hepatic Failure

et al. 2012

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Uncontrolled hepatic immunoactivation is regarded as the primary pathological mechanism of fulminant hepatic failure (FHF). The major acute-phase mediators associated with FHF, including IL-1β, IL-6, and TNF-α, impair the regeneration of liver cells and stem cell grafts. Amniotic-fluid–derived mesenchymal stem cells (AF-MSCs) have the capacity, under specific conditions, to differentiate into hepatocytes. Interleukin-1–receptor antagonist (IL-1Ra) plays an anti-inflammatory and anti-apoptotic role in acute and chronic inflammation, and has been used in many experimental and clinical applications. In the present study, we implanted IL-1Ra–expressing AF-MSCs into injured liver via the portal vein, using D-galactosamine–induced FHF in a rat model. IL-1Ra expression, hepatic injury, liver regeneration, cytokines (IL-1β, IL-6), and animal survival were assessed after cell transplantation. Our results showed that AF-MSCs over-expressing IL-1Ra prevented liver failure and reduced mortality in rats with FHF. These animals also exhibited improved liver function and increased survival rates after injection with these cells. Using green fluorescent protein as a marker, we demonstrated that the engrafted cells and their progeny were incorporated into injured livers and produced albumin. This study suggests that AF-MSCs genetically modified to over-express IL-1Ra can be implanted into the injured liver to provide a novel therapeutic approach to the treatment of FHF.

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“…Patients with PALF demonstrating signs of altered mental status and/or worsening coagulopathy should be closely monitored in the ICU with frequent neurological and cardiorespiratory assessments. After initial Table 9.1 Diagnostic evaluation [85] Age -based causes Diagnostic evaluation Idiopathic or indeterminate (all ages) Liver function tests: AST, ALT, GGT, alkaline phosphatase, fractionated bilirubin, albumin, total protein Coagulation: PT-INR, aPTT, fibrinogen, factors V, VII, Ferritin, iron, TIBC Antinuclear antibody, anti-smooth muscle antibody, anti-liver-kidney-microsome antibody, Ig G level, anti-soluble liver antigen/anti-liver pancreas antibody, anti-liver cytosol type I antigen Drug toxicity or accidental ingestion: 1. Infancy: acetaminophen, acetylsalicylic acid, valproic acid, etc.…”

Section: General Principles Of Managementmentioning

confidence: 99%