scholarly journals Design of anti-inflammatory heparan sulfate to protect against acetaminophen-induced acute liver failure

2020 ◽  
Vol 12 (535) ◽  
pp. eaav8075 ◽  
Author(s):  
Katelyn Arnold ◽  
Yongmei Xu ◽  
Erica M. Sparkenbaugh ◽  
Miaomiao Li ◽  
Xiaorui Han ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Heparan Sulfate ◽  
Core Protein ◽  
Lethal Dose ◽  
The United States ◽  
Sterile Inflammation ◽  
Drug Induced ◽  
Apap Overdose ◽  
Acetyl Cysteine

Acetaminophen/paracetamol (APAP) overdose is the leading cause of drug-induced acute liver failure (ALF) in the United States and Europe. The progression of the disease is attributed to sterile inflammation induced by the release of high mobility group box 1 (HMGB1) and the interaction with receptor for advanced glycation end products (RAGE). A specific, effective, and safe approach to neutralize the proinflammatory activity of HMGB1 is highly desirable. Here, we found that a heparan sulfate (HS) octadecasaccharide (18-mer-HP or hepatoprotective 18-mer) displays potent hepatoprotection by targeting the HMGB1/RAGE axis. Endogenous HS proteoglycan, syndecan-1, is shed in response to APAP overdose in mice and humans. Furthermore, purified syndecan-1, but not syndecan-1 core protein, binds to HMGB1, suggesting that HMGB1 binds to HS polysaccharide side chains of syndecan-1. Last, we compared the protection effect between 18-mer-HP and N-acetyl cysteine, which is the standard of care to treat APAP overdose. We demonstrated that 18-mer-HP administered 3 hours after a lethal dose of APAP is fully protective; however, the treatment of N-acetyl cysteine loses protection. Therefore, 18-mer-HP may offer a potential therapeutic advantage over N-acetyl cysteine for late-presenting patients. Synthetic HS provides a potential approach for the treatment of APAP-induced ALF.

scholarly journals Etiology and Outcome of Acute Liver Failure: Experience from a Liver Transplantation Centre in Montreal

2002 ◽  
Vol 16 (10) ◽  
pp. 672-676 ◽  
Author(s):  
Geneviève Tessier ◽  
Edith Villeneuve ◽  
Jean-Pierre Villeneuve
Keyword(s):  
Liver Transplantation ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Rapid Development ◽  
Significant Proportion ◽  
Rare Condition ◽  
Unknown Origin ◽  
The United States ◽  
Drug Induced

BACKGROUND: Acute liver failure is a rare condition in which massive liver injury is associated with the rapid development of hepatic encephalopathy. Although viral hepatitis and drug-induced liver injury are the most common causes, no specific etiology is found in a substantial proportion of cases reported from Europe and the United States.AIM: To determine the etiology and outcome of patients with acute liver failure in the authors’ institution.PATIENTS AND METHODS: The charts of 81 consecutive patients admitted to Saint-Luc between 1991 and 1999 were reviewed.RESULTS: The etiology was viral in 27 cases (33.2%), toxic or drug-induced in 22 (27.2%), of unknown origin in 22 (27.2%) and due to various causes in 10 (12.3%) (autoimmune, vascular, cancer). Of the 81 patients, 16% survived without liver transplantation, and 84% died or underwent liver transplantation. Survival without liver transplantation differed according to the mode of presentation: the survival rate was 27% in patients with hyperacute liver failure, 7% in those with acute liver failure and 0% in those with subacute liver failure. Among the 38 patients who underwent liver transplantation, survival one year after transplantation was 71%. In the 30 patients who died without liver transplantation, the main causes of death were cerebral edema and sepsis.CONCLUSIONS: Acute liver failure is associated with a high mortality, and liver transplantation is the treatment of choice. In a significant proportion of cases, the etiology remains undetermined and is probably related to yet unidentified hepatotropic viruses.

Acute Liver Failure

2016 ◽  
Vol 31 (10) ◽  
pp. 642-653 ◽  
Author(s):  
Carmi S. Punzalan ◽  
Curtis T. Barry
Keyword(s):  
Liver Transplantation ◽  
Hepatic Encephalopathy ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Specific Treatment ◽  
The United States ◽  
Drug Induced ◽  
Life Threatening ◽  
Transplantation Center

Acute liver failure is life threatening liver injury with coagulopathy and hepatic encephalopathy within 26 weeks and generally, in the absence of preexisting liver disease. Fulminant liver failure occurs when hepatic encephalopathy occurs within 8 weeks of jaundice. The majority of patients with ALF are women with the median age of 38 years. In the United States, drug induced liver injury including acetaminophen causes the majority of ALF cases. The etiology of ALF should be determined, if possible, because many causes have a specific treatment. The mainstay for ALF is supportive care and liver transplantation, if necessary. There are multiple prognostic criteria available. Prognosis can be poor and patients should be referred to a liver transplantation center as soon as possible.

scholarly journals Liver transplantation for acute liver failure from drug induced liver injury in the United States

2004 ◽  
Vol 10 (8) ◽  
pp. 1018-1023 ◽  
Author(s):  
Mark W. Russo ◽  
Joseph A. Galanko ◽  
Roshan Shrestha ◽  
Michael W. Fried ◽  
Paul Watkins
Keyword(s):  
United States ◽  
Liver Transplantation ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
The United States ◽  
Drug Induced ◽  
Drug Induced Liver Injury

scholarly journals Acetaminophen: Dose-Dependent Drug Hepatotoxicity and Acute Liver Failure in Patients

2015 ◽  
Vol 33 (4) ◽  
pp. 464-471 ◽  
Author(s):  
Hartmut Jaeschke
Keyword(s):  
Cell Death ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Severe Liver ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Apap Overdose ◽  
Therapeutic Doses ◽  
Dose Dependent

Background: Drug-induced liver injury is a rare but serious clinical problem. A number of drugs can cause severe liver injury and acute liver failure at therapeutic doses in a very limited number of patients (<1:10,000). This idiosyncratic drug-induced liver injury, which is currently not predictable in preclinical safety studies, appears to depend on individual susceptibility and the inability to adapt to the cellular stress caused by a particular drug. In striking contrast to idiosyncratic drug-induced liver injury, drugs with dose-dependent hepatotoxicity are mostly detected during preclinical studies and do not reach the market. One notable exception is acetaminophen (APAP, paracetamol), which is a safe drug at therapeutic doses but can cause severe liver injury and acute liver failure after intentional and unintentional overdoses. Key Messages: APAP overdose is responsible for more acute liver failure cases in the USA or UK than all other etiologies combined. Since APAP overdose in the mouse represents a model for the human pathophysiology, substantial progress has been made during the last decade in understanding the mechanisms of cell death, liver injury and recovery. More recently, emerging evidence based on mechanistic biomarker analysis in patients and studies of cell death in human hepatocytes suggests that most of the mechanisms discovered in mice also apply to patients. The rapid development of N-acetylcysteine as an antidote against APAP overdose was based on the early understanding of APAP toxicity in mice. However, despite the efficacy of N-acetylcysteine in patients who present early after APAP overdose, there is a need to develop intervention strategies for late-presenting patients. Conclusions: The challenges related to APAP toxicity are to better understand the mechanisms of cell death in order to limit liver injury and prevent acute liver failure, and also to develop biomarkers that better predict as early as possible who is at risk for developing acute liver failure with poor outcome.

scholarly journals The Ugly Side of Colchicine

2021 ◽  
Vol 9 ◽  
pp. 232470962110297
Author(s):  
Justin Cozza ◽  
Tuong Vi Cassandra Do ◽  
Shyam Ganti ◽  
Jayaramakrishna Depa
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Activated Charcoal ◽  
The United States ◽  
Multiple Organ ◽  
Poison Control ◽  
Fab Fragments ◽  
Early Use ◽  
Potential Use ◽  
Electrolyte Abnormalities

We report a rare case of a 32-year-old male who ingested 32.4 to 54 mg of colchicine and presented after 44 hours. He developed progressive multiple organ failure with shock, acute kidney failure, troponemia, pancytopenia, absolute neutropenia, disseminated intravascular coagulation, acute liver failure, rhabdomyolysis, and lactic acidosis. He also developed electrolyte abnormalities and refractory hypoglycemia. Initial treatment consisted of activated charcoal, fluids, and broad-spectrum antibiotics with supportive treatment of mechanical ventilation, hemodialysis, vasopressors, N-acetylcysteine, colony-stimulating factors, and blood products. Literature shows potential benefit of colchicine-specific Fab fragments for acute toxicity with limited studies and is not currently available in the United States. Further research for N-acetylcysteine protocol for acute liver failure in colchicine toxicity and potential use of colchicine-specific Fab fragments is needed. Our case demonstrates the importance of early use of activated charcoal for ingestion overdose with the incorporation of poison control into multidisciplinary team for coordinated patient care.

scholarly journals The Role of Acetyl Cysteine in Cocaethylene (Non-Acetaminophen) Acute Liver Failure

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Getaw Worku Hassen ◽  
Amaninder Dhaliwal ◽  
Catherine Ann Jenninigs ◽  
Hossein Kalantari
Keyword(s):  
Emergency Department ◽  
Substance Abuse ◽  
Liver Failure ◽  
Liver Transplant ◽  
Acute Liver Failure ◽  
Active Substance ◽  
Vital Signs ◽  
Normal Limits ◽  
History Of ◽  
Acetyl Cysteine

Background.Acute liver failure can result from acetaminophen overdose, viral infection, toxins, and other disease conditions. Liver transplant is available in limited fashion and the criteria are strict as to who should get an available liver. N- Acetyl Cysteine (NAC) has been used in non-acetaminophen induced liver failure with success. Here we report a case of acute liver failure from cocaethylene that was reversed with NAC along with other medical therapy.Case Presentation.A 50-year-old female patient presented to the Emergency Department (ED) with a two-day history of coffee ground vomiting and hematemesis. She reported occasional substance abuse and heavy alcoholism. She reported shortness of breath and chest pain from the recurrent forceful vomiting. The rest of the review of systems was unremarkable except a fall from intoxication. Physical examination revealed anicteric conjunctiva and nontender abdomen and her vital signs were within normal limits. Initial blood work revealed acute liver and renal failure. The patient was started with general medical management and liver transplant service rejected the case due to active substance abuse. She underwent brief hemodialysis and was started on NAC. Over the course of her hospital stay her liver function and kidney function improved significantly and patient was discharged to home.Conclusion.In cases where liver transplant is not an option for various reasons including active substance abuse, a trial of N-Acetyl Cysteine may be beneficial and should be considered in the Emergency Department.

scholarly journals Drug-Induced Autoimmune Hepatitis From Hydralazine Leading to Acute Liver Failure and Liver Transplantation

2019 ◽  
Vol 6 (10) ◽  
pp. e00252 ◽  
Author(s):  
Jasleen Grewal ◽  
Angela Doan ◽  
Annie S. Hong ◽  
Arpit Amin ◽  
Jason V. Scapa ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Autoimmune Hepatitis ◽  
Drug Induced

P309 PROGNOSTIC MODEL FOR PREDICTING DRUG-INDUCED ACUTE LIVER FAILURE

2014 ◽  
Vol 60 (1) ◽  
pp. S169
Author(s):  
R.J. Andrade ◽  
M. Robles-Díaz ◽  
C. Stephens ◽  
I. Medina-Cáliz ◽  
A. González-Jiménez ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Prognostic Model ◽  
Drug Induced
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