An Investigational Study of BMS-986165 in Participants With Normal Liver Function and Participants With Mild, Moderate and Severe Liver Damage

2019 ◽  
Author(s):  
Keyword(s):  
Liver Function ◽  
Liver Damage ◽  
Normal Liver ◽  
Normal Liver Function ◽  
Severe Liver ◽  
Severe Liver Damage

Heme Induced Organ Failure in Sickle Cell Disease Is Spatiotemporally Determined by the Amount of Heme Released Into the Bloodstream

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2135-2135 ◽  
Author(s):  
Samit Ghosh ◽  
Olufolake Adisa ◽  
Doreen Aryee ◽  
Fang Tan ◽  
Solomon F Ofori-Acquah
Keyword(s):  
Sickle Cell Disease ◽  
Liver Function ◽  
Transgenic Mice ◽  
Sickle Cell ◽  
Liver Damage ◽  
Lung Damage ◽  
Cell Disease ◽  
Long Term Effects ◽  
Severe Liver ◽  
Severe Liver Damage

Abstract Abstract 2135 Circulating heme is scavenged by multiple plasma proteins and delivered to the liver for degradation. We have recently demonstrated that heme scavenging is variably impaired in transgenic mice with sickle cell disease (SCD). In this study, we tested the hypothesis that excess protein-free plasma heme (PFPH) in the blood circulation, and excess scavenged protein-bound plasma heme (PBPH) destined for degradation cause different types of organ damage in SCD. Transgenic mice expressing exclusively human sickle hemoglobin (SS) were intravenously injected with a dose of heme (25 micromoles/kg) to elevate PBPH only, or with a dose (70 micromoles/kg) sufficient to raise PFPH. In agreement with our previous findings, PFPH was associated with severe lung injury and 100% lethality within 2 hours. This phenomenon occurred independent of any liver involvement. Modest elevation of circulating heme sufficient to raise PBPH only, increased alanine aminotransferase and aspartate aminotranferase 3- to 4-fold (P<0.001) within 12 hours, caused 55% lethality by 72 hours, with severe liver damage but no lung involvement. There was no effect on lung and liver function in control AA and AS mice administered the same doses of heme given to the SS mice. Recombinant human hemopexin rescued SS mice from heme induced lung damage and sudden death, however, the same group of mice developed severe liver damage and succumbed 24–48 hours later. Finally, in a cohort of 27 patients with SCD, a sudden drop in hemoglobin of 0.5 to 4.0 g/dl was associated with a marked increase in ALT 3–7 days later (p=0.027). Collectively, these results show for the first time that acute elevation of circulating heme causes two distinct organ pathologies with different mortality profiles in SCD. Therapeutic strategies based solely on enhanced scavenging of excess heme may provide short-term pulmonary benefits with deleterious long-term effects on liver function. Disclosures: Ofori-Acquah: Emory University: Patents & Royalties.

Acetaminophen Oxidation and Inflammatory Markers – A Review of Hepatic Molecular Mechanisms and Preclinical Studies

2020 ◽  
Vol 21 (12) ◽  
pp. 1225-1236
Author(s):  
Silvio Terra Stefanello ◽  
Nelson Rodrigues de Carvalho ◽  
Simone Beder Reis ◽  
Felix Alexandre Antunes Soares ◽  
Rômulo Pillon Barcelos
Keyword(s):  
Liver Damage ◽  
Inflammatory Markers ◽  
Molecular Mechanisms ◽  
Easy Access ◽  
Timely Manner ◽  
Severe Liver ◽  
Clinical Biomarkers ◽  
Severe Liver Damage ◽  
Acetaminophen Intoxication ◽  
New Biomarkers

Acetaminophen is a widely used analgesic for pain management, especially useful in chronic diseases, such as rheumatoid arthritis. However, easy access to this medicine has increased the occurrence of episodes of poisoning. Patients often develop severe liver damage, which may quickly lead to death. Consequently, numerous studies have been conducted to identify new biomarkers that allow the prediction of the degree of acetaminophen intoxication and thus intervene in a timely manner to save patients’ lives. This review highlights the main mechanisms of the induction and progression of liver damage arising from acetaminophen poisoning. In addition, we have discussed the possibility of using new clinical biomarkers for detecting acetaminophen poisoning.

scholarly journals Analysis of common causes of liver damage among children 12 years and younger in Weifang

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110066
Author(s):  
Qinghong Meng ◽  
Na Li ◽  
Lianmei Yuan ◽  
Xiaona Gao
Keyword(s):  
Liver Damage ◽  
Epstein Barr Virus ◽  
Metabolic Diseases ◽  
Unknown Etiology ◽  
Severe Liver ◽  
Drug Induced ◽  
Barr Virus ◽  
Common Causes ◽  
Severe Liver Damage ◽  
Epstein Barr

Aims To explore the causes of liver damage among children 12 years and younger in Weifang and to provide a theoretical basis for early diagnosis of liver damage in children. Methods Retrospective study of clinical data from pediatric patients (age ≤12 years) with liver damage in diagnosed at Weifang People's Hospital from June 2010 to May 2020. Results A total of 2632 children (1572 boys, 1060 girls) aged ≤12 years were diagnosed with liver damage including infectious liver damage (2100 cases), non-infectious liver damage (446 cases) and liver damage of unknown etiology (86 cases). The most common causes of infectious liver damage were viral infection (1515 cases), Mycoplasma pneumoniae infection (343 cases), and bacterial infection (197 cases). The most common causes of viral liver damage were Epstein–Barr virus, cytomegalovirus, and enterovirus. The most common causes of non-infectious liver damage were drug-induced liver damage, Kawasaki disease, and genetic metabolic diseases. There were 31 cases of severe liver damage. Conclusion There were many causes of liver damage among children in Weifang. Infections, and especially viral infections such as Epstein–Barr virus, were the most common causes of liver damage. Severe liver damage was primarily caused by drugs or poisons.

Management of Obscurely Dilated Common Bile Duct with Normal Liver Function Tests: A Pragmatic Approach

2021 ◽  
Author(s):  
Sundeep Singh Saluja ◽  
Vaibhav Kumar Varshney ◽  
Vidya Sharada Bhat ◽  
Phani Kumar Nekarakanti ◽  
Asit Arora ◽  
...  
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Liver Function ◽  
Normal Liver ◽  
Liver Function Tests ◽  
Pragmatic Approach ◽  
Normal Liver Function ◽  
Function Tests

Persistently raised aspartate aminotransferase (AST) due to macro-AST in a rheumatology clinic

Diagnosis ◽  
2015 ◽  
Vol 2 (2) ◽  
pp. 137-140 ◽  
Author(s):  
Wycliffe Mbagaya ◽  
Joanne Foo ◽  
Ahai Luvai ◽  
Claire King ◽  
Sarah Mapplebeck ◽  
...  
Keyword(s):  
Liver Function ◽  
Aspartate Aminotransferase ◽  
Normal Liver ◽  
Abdominal Ultrasound ◽  
Liver Function Tests ◽  
Analytical Investigation ◽  
Normal Liver Function ◽  
Rheumatology Clinic ◽  
History Of ◽  
Liver Biopsies

AbstractMacrocomplexes between immunoglobins and aspartate aminotransferase (macro-AST) may result in persistently increased AST concentration. The presence of macro-AST in patients has been implicated in unnecessary investigations of abnormal liver function tests. We report the case of a 44-year-old female who presented to the rheumatology clinic with a 12-months’ history of constant widespread pain affecting her limbs and was found to have an elevated AST concentration. Further information from her GP revealed a 14-years’ history of elevated AST with otherwise normal liver function. Previous abdominal ultrasound and two liver biopsies carried out 2 years apart were normal. This prompted further analytical investigation by the biochemistry department which identified macro-AST as the cause. This case illustrates that persistently raised isolated AST concentration with no other abnormal indices may warrant macroenzyme analysis potentially avoiding unnecessary invasive investigations.

Analysis of Factors Responsible for Continuing Mortality after Paracetamol Overdose

1986 ◽  
Vol 5 (3) ◽  
pp. 201-206 ◽  
Author(s):  
R. B. Read ◽  
J. M. Tredger ◽  
R. Williams
Keyword(s):  
Liver Failure ◽  
Liver Damage ◽  
Paracetamol Overdose ◽  
Severe Liver ◽  
College Hospital ◽  
King's College ◽  
Accident And Emergency ◽  
Drinking History ◽  
Severe Liver Damage ◽  
Complete Series

1 To determine reasons for the continuing mortality in patients taking a paracetamol overdose, the presentation, drug ingestion history, patient background, use of antidote ( N-acetylcysteine and methionine), clinical course and outcome were determined in 247 patients treated at King's College Hospital in 1982 and 1983. Patients (147) were referred from other centres because of severe liver damage and 100 were local patients seen in the accident and emergency department. 2 Survival in the local patients was 100% and, for those with severe liver damage, 49 and 63% (1982 and 1983 values). Delay in initial presentation to hospital was a major factor in determination of an adverse outcome, with a median delay of 30 h in the referred patients and 8 h in the local cases. Such a delay precluded administration of antidote to the majority of patients in the referred group, but in 11 cases where antidote could have been given a full course was not provided and all 11 patients died. Included among these were four patients in whom the serum paracetamol concentration was in the ‘non-toxic’ range. 3 One patient with a chronic alcohol-drinking history (> 200 g/day) received N-acetylcysteine at 12 h but died from liver failure. However, in the complete series prior alcohol consumption was not associated with a significantly worse prognosis and simultaneous ingestion of alcohol with paracetamol had no effect on outcome. 4 The concomitant ingestion of dextropropoxyphene caused an early and marked impairment of consciousness unrelated to any hepatotoxicity but, in three cases where dextropropoxyphene combinations were used, death occurred subsequently from liver failure.

scholarly journals Mildly elevated succinylacetone and normal liver function in compound heterozygotes with pathogenic and pseudodeficient FAH alleles

2018 ◽  
Vol 14 ◽  
pp. 55-58 ◽  
Author(s):  
Hao Yang ◽  
Francis Rossignol ◽  
Denis Cyr ◽  
Rachel Laframboise ◽  
Shu Pei Wang ◽  
...  
Keyword(s):  
Liver Function ◽  
Normal Liver ◽  
Normal Liver Function ◽  
Compound Heterozygotes

Sodium valproate reassessed

1981 ◽  
Vol 19 (24) ◽  
pp. 93-95
Keyword(s):  
Sodium Valproate ◽  
Liver Damage ◽  
Severe Liver ◽  
Severe Liver Damage ◽  
The Uk

Sodium valproate (Epilim - Labaz) is an effective anticonvulsant which has been used in the treatment of most forms of epilepsy. It has been taken by nearly a million people (70,000 in the UK) and during its first 10 years reported unwanted effects were few and mild.1 The recent reports of severe liver damage and other serious unwanted effects are disturbing.

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