scholarly journals L-Arginine and Asymmetric Dimethylarginine Are Early Predictors for Survival in Septic Patients with Acute Liver Failure

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Thorsten Brenner ◽  
Thomas H. Fleming ◽  
Claudia Rosenhagen ◽  
Ute Krauser ◽  
Markus Mieth ◽  
...  
Keyword(s):  
Septic Shock ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Healthy Volunteers ◽  
Asymmetric Dimethylarginine ◽  
Plasma Concentrations ◽  
Hepatic Function ◽  
Surgical Patients ◽  
Enzyme Linked Immunosorbent Assay ◽  
Early Predictors

Dysfunctions of the L-arginine (L-arg)/nitric-oxide (NO) pathway are suspected to be important for the pathogenesis of multiple organ dysfunction syndrome (MODS) in septic shock. Therefore plasma concentrations of L-arg and asymmetric dimethylarginine (ADMA) were measured in 60 patients with septic shock, 30 surgical patients and 30 healthy volunteers using enzyme linked immunosorbent assay (ELISA) kits. Plasma samples from patients with septic shock were collected at sepsis onset, and 24 h, 4 d, 7 d, 14 d and 28 d later. Samples from surgical patients were collected prior to surgery, immediately after the end of the surgical procedure as well as 24 h later and from healthy volunteers once. In comparison to healthy volunteers and surgical patients, individuals with septic shock showed significantly increased levels of ADMA, as well as a decrease in the ratio of L-arg and ADMA at all timepoints. In septic patients with an acute liver failure (ALF), plasma levels of ADMA and L-arg were significantly increased in comparison to septic patients with an intact hepatic function. In summary it can be stated, that bioavailability of NO is reduced in septic shock. Moreover, measurements of ADMA and L-arg appear to be early predictors for survival in patients with sepsis-associated ALF.

scholarly journals Acute liver failure in a term neonate after repeated paracetamol administration

2014 ◽  
Vol 32 (1) ◽  
pp. 144-148 ◽  
Author(s):  
Fabio Bucaretchi ◽  
Carla Borrasca Fernandes ◽  
Maira Migliari Branco ◽  
Eduardo Mello De Capitani ◽  
Stephen Hyslop ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Hepatic Function ◽  
Term Neonate ◽  
Intestinal Bleeding ◽  
Older Children ◽  
Laboratory Findings ◽  
Serum Aminotransferase ◽  
Severe Hepatotoxicity ◽  
Hepatocellular Damage

Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L), hypoglycemia (18mg/dL), increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L) and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL) after receiving oral paracetamol (10mg/kg/dose every 4 hours) for three consecutive days (total dose around 180mg/kg; serum concentration 36-48 hours after the last dose of 77µg/ mL). Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. Comments: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione - which provides greater resistance after overdoses -, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone) that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days.

scholarly journals The Use of Methylene Blue during Liver Transplantation for Vasoplegia

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Paul Harding ◽  
Thomas Nicholas ◽  
Cale Kassel
Keyword(s):  
Septic Shock ◽  
Methylene Blue ◽  
Liver Transplantation ◽  
Cardiopulmonary Bypass ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Treatment Option ◽  
Case Reports ◽  
Refractory Hypotension

The use of methylene blue for vasoplegia in cardiac cases with cardiopulmonary bypass, septic shock, and acute liver failure is well documented. Use of MB for liver transplantation has been largely limited to case reports. We describe three separate liver transplantation patients with significant hypotension following reperfusion. Administration of methylene blue to each patient resulted in a significant decrease in vasopressor medication and two patients weaned completely. We argue that the use of MB should be considered as a treatment option for refractory hypotension.

scholarly journals Insight into microRNAs-Mediated Communication between Liver and Brain: A Possible Approach for Understanding Acute Liver Failure?

2021 ◽  
Vol 23 (1) ◽  
pp. 224
Author(s):  
Karolina Orzeł-Gajowik ◽  
Krzysztof Milewski ◽  
Magdalena Zielińska
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Blood Brain Barrier ◽  
Neuropsychiatric Symptoms ◽  
Hepatic Function ◽  
Brain Barrier ◽  
Circulating Mirnas ◽  
Blood Brain ◽  
Micro Rnas ◽  
Functional Components

Acute liver failure (ALF) is a life-threatening consequence of hepatic function rapid loss without preexisting liver disease. ALF may result in a spectrum of neuropsychiatric symptoms that encompasses cognitive impairment, coma, and often death, collectively defined as acute hepatic encephalopathy (HE). Micro RNAs are small non-coding RNAs that modulate gene expression and are extensively verified as biomarker candidates in various diseases. Our systematic literature review based on the last decade’s reports involving a total of 852 ALF patients, determined 205 altered circulating miRNAs, of which 25 miRNAs were altered in the blood, regardless of study design and methodology. Selected 25 miRNAs, emerging predominantly from the analyses of samples obtained from acetaminophen overdosed patients, represent the most promising biomarker candidates for a diagnostic panel for symptomatic ALF. We discussed the role of selected miRNAs in the context of tissue-specific origin and its possible regulatory role for molecular pathways involved in blood–brain barrier function. The defined several common pathways for 15 differently altered miRNAs were relevant to cellular community processes, indicating loss of intercellular, structural, and functional components, which may result in blood-brain barrier impairment and brain dysfunction. However, a causational relationship between circulating miRNAs differential expression, and particular clinical features of ALF, has to be demonstrated in a further study.

scholarly journals Bifidobacterium longum R0175 Protects Rats against D-Galactosamine-Induced Acute Liver Failure

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Kaicen Wang ◽  
Longxian Lv ◽  
Ren Yan ◽  
Qiangqiang Wang ◽  
Huiyong Jiang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Protective Efficacy ◽  
Bifidobacterium Longum ◽  
Plasma Concentrations ◽  
Protective Effects ◽  
Content Type ◽  
Intestinal Microbes ◽  
Relative Abundances

ABSTRACT Acute liver failure is a severe liver disorder that poses considerable global challenges. Previous studies on Bifidobacterium longum R0175 have mainly focused on its psychotropic functions. The current research focused on the protective efficacy of B. longum R0175 against acute liver failure caused by d-galactosamine (d-GalN) in rats and further tested the hypothesis that B. longum R0175 exerted liver-protective effects by affecting the intestinal microbiota and fecal metabolites and by inhibiting inflammation. We found that oral gavage of B. longum R0175 markedly reduced the severity of liver injury in d-GalN-treated rats, as evidenced by decreased serum levels of aspartate aminotransferase (AST) and total bile acids (TBAs) (P < 0.05). Moreover, the plasma concentrations of proinflammatory cytokines (interleukin 1β [IL-1β] and tumor necrosis factor-α [TNF-α]) and chemokines (granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage chemoattractant protein 1 [MCP-1], chemokine [C-X-C motif] ligand 1 [CXCL1], chemokine [C-C motif] ligand 5 [CCL5], and macrophage inflammatory protein-1α [MIP-1α]) were also markedly reduced (P < 0.05). Pretreatment with B. longum R0175 partially reversed the gut microbiota dysbiosis in rats with liver injury by increasing the relative abundances of potentially beneficial bacteria, such as Alloprevotella spp., and decreasing the relative abundances of potentially harmful bacteria, such as Acetatifactor muris, Butyricimonas spp., and Oscillibacter spp. Furthermore, B. longum R0175 administration partially improved the metabolic function of the intestinal microbes, as indicated by the decreased level of lithocholic acid found in the feces. IMPORTANCE Our research investigated the protective and preventive roles of B. longum R0175 in a rat model of acute liver failure. The results illustrated that this probiotic strain exhibited protective effects in rats with acute liver failure. Thus, B. longum R0175 showed clinical application prospects that required further exploration.

Hemodynamics and metabolic studies on septic shock in patients with acute liver failure

2008 ◽  
Vol 23 (4) ◽  
pp. 468-472 ◽  
Author(s):  
Ming-Hung Tsai ◽  
Yung-Chang Chen ◽  
Jau-Min Lien ◽  
Ya-Chung Tian ◽  
Yun-shing Peng ◽  
...  
Keyword(s):  
Septic Shock ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Metabolic Studies

An extracorporeal bioartificial liver embedded with 3D-layered human liver progenitor-like cells relieves acute liver failure in pigs

2020 ◽  
Vol 12 (551) ◽  
pp. eaba5146
Author(s):  
Wei-Jian Li ◽  
Xue-Jing Zhu ◽  
Tian-Jie Yuan ◽  
Zhen-Yu Wang ◽  
Zheng-Qian Bian ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Porcine Model ◽  
Three Dimensional ◽  
Hepatic Function ◽  
Bioartificial Liver ◽  
Hepatic Cells ◽  
Support Device ◽  
Human Primary Hepatocytes ◽  
Therapeutic Avenue

Clinical advancement of the bioartificial liver is hampered by the lack of expandable human hepatocytes and appropriate bioreactors and carriers to encourage hepatic cells to function during extracorporeal circulation. We have recently developed an efficient approach for derivation of expandable liver progenitor-like cells from human primary hepatocytes (HepLPCs). Here, we generated immortalized and functionally enhanced HepLPCs by introducing FOXA3, a hepatocyte nuclear factor that enables potentially complete hepatic function. When cultured on macroporous carriers in an air-liquid interactive bioartificial liver (Ali-BAL) support device, the integrated cells were alternately exposed to aeration and nutrition and grew to form high-density three-dimensional constructs. This led to highly efficient mass transfer and supported liver functions such as albumin biosynthesis and ammonia detoxification via ureagenesis. In a porcine model of drug overdose–induced acute liver failure (ALF), extracorporeal Ali-BAL treatment for 3 hours prevented hepatic encephalopathy and led to markedly improved survival (83%, n = 6) compared to ALF control (17%, n = 6, P = 0.02) and device-only (no-cell) therapy (0%, n = 6, P = 0.003). The blood ammonia concentrations, as well as the biochemical and coagulation indices, were reduced in Ali-BAL–treated pigs. Ali-BAL treatment attenuated liver damage, ameliorated inflammation, and enhanced liver regeneration in the ALF porcine model and could be considered as a potential therapeutic avenue for patients with ALF.

Molecular Adsorbent Recirculating System Effectively Replaces Hepatic Function in Severe Acute Liver Failure

2017 ◽  
Vol 266 (4) ◽  
pp. 677-684 ◽  
Author(s):  
Steven I. Hanish ◽  
Deborah M. Stein ◽  
Joseph R. Scalea ◽  
Eno-obong Essien ◽  
Paul Thurman ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Hepatic Function ◽  
Molecular Adsorbent Recirculating System ◽  
Molecular Adsorbent

Arginine, citrulline and nitric oxide metabolism in sepsis

2009 ◽  
Vol 117 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Christina C. Kao ◽  
Venkata Bandi ◽  
Kalpalatha K. Guntupalli ◽  
Manhong Wu ◽  
Leticia Castillo ◽  
...  
Keyword(s):  
Septic Shock ◽  
Asymmetric Dimethylarginine ◽  
De Novo ◽  
Plasma Concentrations ◽  
No Synthase ◽  
Whole Body ◽  
Healthy Controls ◽  
Protein Breakdown ◽  
Breakdown Rate ◽  
Body Protein

Arginine has vasodilatory effects, via its conversion by NO synthase into NO, and immunomodulatory actions which play important roles in sepsis. Protein breakdown affects arginine availability and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore affect NO synthesis in patients with sepsis. The objective of the present study was to investigate whole-body in vivo arginine and citrulline metabolism and NO synthesis rates, and their relationship to protein breakdown in patients with sepsis or septic shock and in healthy volunteers. Endogenous leucine flux, an index of whole-body protein breakdown rate, was measured in 13 critically ill patients with sepsis or septic shock and seven healthy controls using an intravenous infusion of [1-13C]leucine. Arginine flux, citrulline flux and the rate of conversion of arginine into citrulline (an index of NO synthesis) were measured with intravenous infusions of [15N2]guanidino-arginine and [5,5-2H2]citrulline. Plasma concentrations of nitrite plus nitrate, arginine, citrulline and asymmetric dimethylarginine were measured. Compared with controls, patients had a higher leucine flux and higher NO metabolites, but arginine flux, plasma asymmetric dimethylarginine concentration and the rate of NO synthesis were not different. Citrulline flux and plasma arginine and citrulline were lower in patients than in controls. Arginine production was positively correlated with the protein breakdown rate. Whole-body arginine production and NO synthesis were similar in patients with sepsis and septic shock and healthy controls. Despite increased proteolysis in sepsis, there is a decreased arginine plasma concentration, suggesting inadequate de novo synthesis secondary to decreased citrulline production.

Sign in / Sign up

Export Citation Format

Share Document