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 Sanghuangporus sanghuang Mycelium Prevents Paracetamol-Induced Hepatotoxicity through Regulating the MAPK/NF-κB, Keap1/Nrf2/HO-1, TLR4/PI3K/Akt and CaMKKβ/LKB1/AMPK Pathways and Suppressing Oxidative Stress and Inflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 897
Author(s):  
Wen-Ping Jiang ◽  
Jeng-Shyan Deng ◽  
Shyh-Shyun Huang ◽  
Sheng-Hua Wu ◽  
Chin-Chu Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Molecular Evidence ◽  
Related Factor ◽  
Serum Aminotransferase ◽  
Compound C

Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before paracetamol treatment. SS decreased serum aminotransferase activities and the lipid profiles, protecting against paracetamol hepatotoxicity in mice. Furthermore, SS inhibited the lipid peroxidation marker malondialdehyde (MDA), hepatic cytochrome P450 2E1 (CYP2E1), and the histopathological changes in the liver and decreased inflammatory activity by inhibiting the production of proinflammatory cytokines in paracetamol-induced acute liver failure. Moreover, SS improved the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in the liver. Significantly, SS diminished mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the nuclear factor-kappa B (NF-κB) axis, as well as upregulated the Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, in paracetamol-induced mice. SS mainly inhibited the phosphorylation of the liver kinase B1 (LKB1), Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ), and AMP-activated protein kinase (AMPK) protein expression. Furthermore, the protective effects of SS on paracetamol-induced hepatotoxicity were abolished by compound C, an AMPK inhibitor. In summary, we provide novel molecular evidence that SS protects liver cells from paracetamol-induced hepatotoxicity by inhibiting oxidative stress and inflammation.

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.

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

Acute Liver Failure - It's Just a Matter of Cell Death

2016 ◽  
Vol 34 (4) ◽  
pp. 423-428 ◽  
Author(s):  
Jan-Peter Sowa ◽  
Guido Gerken ◽  
Ali Canbay
Keyword(s):  
Cell Death ◽  
Intensive Care ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Clinical Management ◽  
Significant Proportion ◽  
Specific Treatment ◽  
Scoring Systems ◽  
Hepatic Function ◽  
Drug Induced

Background: Acute liver failure (ALF) is characterized by a sudden loss of hepatic function due to hepatocyte cell death and dysfunction in previously healthy individuals. The clinical presentation of ALF is associated with coagulopathy (international normalized ratio ≥1.5) and hepatic encephalopathy, although the latter may be less pronounced. Without appropriate and timely intensive care or liver transplantation (LTx), ALF will result in multi-organ failure and death. Various causes may induce ALF, with acetaminophen (APAP) intoxication and acute hepatitis B infection as most common causes in industrialized countries. While conventional terminology discerns acute, acute-on-chronic and acute-on cirrhosis liver failure, some chronic liver diseases (i.e. autoimmune hepatitis (AIH), Wilson's disease) can remain undiagnosed until an initial presentation as ALF. Key Messages: Upon definite diagnosis of ALF, the underlying cause must be identified, since etiology affects prognosis and clinical management. Individual prognosis should be evaluated with one of various available scoring systems. Most widely used are Model for End-Stage Liver Disease, the King's College Criteria and the Clichy criteria. Other markers, that is, cell death markers, lactate or thyroid status, may improve diagnostic accuracy of classic scores, though routine use of these is not yet established. Etiology-specific treatment under intensive care should be performed, if possible (APAP and amanita intoxication, acute viral hepatitides and AIH). LTx is the only curative option for other causes, unknown reasons of ALF or when etiology-specific therapy fails. In ambiguous cases, that is, suspected drug induced ALF or AIH, co-infection with hepatitis E virus should be tested, as this might be more common than it is currently supposed to be. Conclusions: Despite major improvements in clinical management of ALF patients, a significant proportion of ALF cases remains without clear identification of the underlying cause or unrecognized multiple causes. In depth analyzes of ambiguous ALF cases is warranted to further improve clinical management.

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 as the Leading Manifestation of Spontaneous Tumour Lysis Syndrome in a Patient with NonHodgkin Lymphoma: Do Current Diagnostic Criteria of Tumour Lysis Syndrome Need Re-Evaluation?

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Janja Tarčuković ◽  
Lara Valenčić ◽  
Željka Polonijo ◽  
Ana Fućak ◽  
Boban Dangubić ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Multiorgan Failure ◽  
Clinical Manifestations ◽  
Tumour Lysis Syndrome ◽  
Sterile Inflammation ◽  
Metabolic Disturbances ◽  
Laboratory Findings ◽  
Tumour Lysis ◽  
Nonhodgkin Lymphoma

Tumour lysis syndrome (TLS) is a group of pathophysiological processes caused by rapid degradation of tumour cells with subsequent release of intracellular contents into the extracellular space. It is characterized by the development of systemic metabolic disturbances with or without clinical manifestations. The process usually occurs in highly proliferative, large tumours after induction of cytotoxic therapy. Rarely, however, spontaneous TLS can develop, as well as signs of multiorgan failure triggered by an excessive metabolic load and sterile inflammation. The combination of the aforementioned is thus quite unique. Here, we present a 63-year-old male in which spontaneous TLS was accompanied with acute liver failure and delineated underlying nonHodgkin lymphoma. Initial laboratory findings included hyperkalaemia, hyperphosphataemia, hypocalcaemia, uraemia, and increased creatinine levels indicating the onset of TLS with acute kidney injury. Moreover, the patient showed signs of jaundice, coagulopathy, and hepatic encephalopathy. Development of TLS with multiorgan failure prompted rapid initiation of critical care management, including vigorous intravenous fluid therapy, allopurinol treatment, high flow continuous venovenous haemodiafiltration, and commencement of chemotherapy. The case highlights the possibility of TLS as a differential diagnosis in patients presenting with multiorgan failure and the importance of early detection of this potentially challenging and fatal diagnosis.

scholarly journals Early Detection and Rescue of an Unusual Case of Pediatric Acute Liver Failure Associated with Secondary Hemophagocytic Lymphophagocytosis: Case Report from a Liver Transplant Center in India

2021 ◽  
Vol 11 (01) ◽  
pp. e141-e144
Author(s):  
Richa Mittal ◽  
Smita Malhotra ◽  
Nameet Jerath ◽  
Amita Mahajan ◽  
Anupam Sibal
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Influenza A ◽  
Early Recognition ◽  
Central Nervous System Involvement ◽  
Laboratory Findings ◽  
Clinical Criteria ◽  
Life Saving ◽  
Influenza A H1n1 ◽  
Pediatric Acute Liver Failure

AbstractHemophagocytic lymphohistiocytosis (HLH) is a rare, multisystem, potentially fatal clinicopathologic syndrome. HLH presenting predominantly as pediatric acute liver failure (PALF) has been rarely reported. Early recognition is imperative to initiate life-saving treatment but is often hampered due to the rarity of this syndrome, variable clinical presentations, and nonspecific clinical and laboratory findings. In this article, we reported a case of secondary HLH (H1N1 and RSV positive) presenting as PALF from India. A previously healthy 22-month-old boy presented with fever, vomiting, and altered sensorium for 10 days. He had coagulopathy and deranged liver functions. He was evaluated for underlying etiology and managed on lines of PALF. Due to persistent bicytopenia and excessively high ferritin levels, HLH was strongly suspected though he did not fulfill all clinical criteria for the diagnosis of HLH. Presence of seizures and cerebrospinal fluid analysis was suggestive of central nervous system involvement. There was no evidence of primary HLH on genetic evaluation. Real-time polymerase chain reaction amplifications were positive for RSV and influenza A H1N1, confirming the causative triggers. After the administration of immunosuppressants and oseltamivir, the patient's symptoms improved dramatically and he recovered completely. To the best of our knowledge, this is the fourth case reported worldwide till date of successful rescue of ALF in a child associated with HLH completely without resorting to liver transplantation. Clinical vigilance is crucial for possible presence of HLH with varied initial presentations in PALF despite incomplete diagnostic criteria, with detailed etiological workup for commencing life-saving therapy in time.

Frequency of flutamide induced hepatotoxicity in patients with prostate carcinoma

1999 ◽  
Vol 18 (3) ◽  
pp. 137-140 ◽  
Author(s):  
Mustafa Çetin ◽  
Deniz Demirci ◽  
Ali Ünal ◽  
Mustafa Altinbaş ◽  
Muhammed Güven ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Liver Function ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Enzyme ◽  
Prostate Carcinoma ◽  
Liver Function Tests ◽  
The Other ◽  
Who Criteria ◽  
Severe Hepatotoxicity

To identify and describe the frequency and severity of hepatotoxicity in patients who received flutamide therapy for prostate cancer, 22 patients were treated with the combination of flutamide and goserilin or orchiectomy. After diagnosis and staging of prostate cancer, baseline results were obtained for a set of five liver function tests (LF Ts). Hepatotoxicity was assessed according to the WHO criteria. After initiation of flutamide therapy, LF Ts were performed at 4, 8 and 12 weeks and every 2 months thereafter. Severe hepatotoxicity appeared in two of 22 (9%) patients. Following the discontinuation of flutamide, one patient died due to acute liver failure. On the other patient an improvement of LF Ts occurred after cessation of flutamide. The observed severe hepatotoxicity in two of 22 (9%) patients occurred more frequent than is predicted in the literature. Patients treated with flutamide, having symptomatic or asymptomatic liver enzyme elevations, should be taken off therapy as soon as possible.

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