scholarly journals Optimizing diagnostic approach to drug-induced liver injury

2018 ◽  
Vol 12 (3) ◽  
pp. 180-189 ◽  
Author(s):  
Maria Giovanna Minissale ◽  
Maurizio Soresi ◽  
Massimo Galia ◽  
Francesco Agnello ◽  
Lydia Giannitrapani ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Damage ◽  
Transient Elastography ◽  
Liver Stiffness ◽  
Abdominal Ultrasound ◽  
Liver Function Tests ◽  
Accurate Method ◽  
Focal Lesions ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Drug-induced liver injury (DILI) is often a trial even to expert clinicians, because sometimes diagnosis is not easy to be made. Guidelines of the American College of Gastroenterology (ACG) yielded in 2014, help to better understand the problem. The diagnosis of DILI is made through a detailed evaluation of clinical, serological, radiological and histological aspects. Biochemical data include liver function tests that allow to assess the pattern of damage, such as hepatocellular, cholestatic and mixed liver injury; serological data include testing for major and possibly minor hepatotropic viruses, non-organ specific autoantibodies. Clinical scenario might include jaundice, nausea, vomiting and extra-hepatic manifestations such as fever, pruritus, rash and eosinophilia. Investigation of the potential culprit drugs should involve firstly the temporal relationship between intake of the medication and onset of symptoms, thus the improvement after drug withdrawal. Overall, to complete the diagnostic evaluation, an abdominal ultrasound can be performed, as well as measurement of liver stiffness by transient elastography, and finally liver biopsy, which still represents the most accurate method to definitely assess liver damage. Sometimes, in such cases, computed tomography scan and magnetic resonance could help in the diagnosis of cases presenting with focal lesions of the liver, with cholestatic-like disease or vascular alterations, such as veno-occlusive disease. DILI diagnostic criteria help clinicians thinking of liver injury induced by drug, excluding other causes of liver disease. According to severity of liver damage and type of drug, it is possible to carefully predict the patient’s outcome.

scholarly journals BML-257, a small molecule that protects against drug induced liver injury in zebrafish

2022 ◽  
Author(s):  
Urmila Jagtap ◽  
Sandeep Basu ◽  
Lavanya Lokhande ◽  
Nikhil Bharti ◽  
Chetana Sachidanandan
Keyword(s):  
Liver Injury ◽  
Small Molecule ◽  
Liver Damage ◽  
Protective Action ◽  
Damage Model ◽  
Akt Inhibitor ◽  
Drug Induced ◽  
Specific Expression ◽  
Drug Induced Liver Injury ◽  
Chemical Screen

The use of many essential drugs is restricted due to their deleterious effects on the liver. Molecules that can prevent or protect the liver from drug induced liver injury (DILI) would be valuable in such situations. We used hepatocyte-specific expression of bacterial nitroreductase in zebrafish to cause temporally controlled liver damage. This transgenic line was used to run a whole organism based chemical screen in zebrafish larvae. In this screen we identified BML-257, a potent small molecule AKT inhibitor, that protected the liver against metronidazole-induced liver injury. BML-257 also showed potent prophylactic and pro-regenerative activity in this liver damage model. BML-257 also showed remarkable protective action in two independent toxicological models of liver injury caused by acetaminophen and Isoniazid. This suggests that BML-257 may have the potential to protect against multiple kinds of drug induced liver injury.

Drugs and liver damage

2010 ◽  
pp. 2527-2537
Author(s):  
J. Neuberger
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Pulmonary Tuberculosis ◽  
Liver Damage ◽  
Case History ◽  
Genetic Component ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Almost All

Case History—A 22 yr old man, being treated for pulmonary tuberculosis, now presenting with confusion and jaundice. Drug-induced liver injury (DILI) is relatively uncommon but can very rarely be fatal. Almost all patterns of liver disease can be induced by drugs, and some drugs may be associated with more than one type of reaction. Some cases of DILI have a genetic component. Most cases present with jaundice and/or hepatitis....

scholarly journals A Patient with Nafcillin-Associated Drug-Induced Liver Failure

2017 ◽  
Vol 11 (3) ◽  
pp. 564-568 ◽  
Author(s):  
Qin Rao ◽  
Isaiah Schuster ◽  
Talal Seoud ◽  
Kevin Zarrabi ◽  
Nirvani Goolsarran
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Liver Failure ◽  
Acute Liver Injury ◽  
Early Recognition ◽  
Antibiotic Use ◽  
Liver Function Tests ◽  
The United States ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Nafcillin-induced acute liver injury is a rare and potentially fatal complication that has been known since the 1960s but inadequately studied. At this time, the only proven treatment is early discontinuation of the drug. Because of the high prevalence of nafcillin class antibiotic use in the United States, it is important for clinicians to have a high clinical suspicion for this diagnosis. We present a case of liver failure attributable to nafcillin use in a 68-year-old male with a history methicillin-sensitive Staphylococcus and L3/L4 osteomyelitis. After starting long-term antibiotic therapy, he presented with painless jaundice which necessitated discontinuation of the drug. At the time of presentation, the patient’s lab work exhibited a bilirubin/direct bilirubin of 9.4/8.2 mg/dL, alkaline phosphatase of 311 IU/L, and aspartate transaminase/alanine transaminase of 109/127 IU/L. The patient was switched to i.v. vancomycin given the concern for drug-induced liver injury. Imaging did not show obstruction of the hepatobiliary or pancreaticobiliary trees. Serology was unremarkable for viral etiology, autoimmune processes, Wilson disease, and hemochromatosis. A liver biopsy showed findings consistent with drug-induced liver injury. The patient’s liver function tests peaked at day 7 of admission and trended towards normal levels with cessation of nafcillin therapy. The patient was discharged with a diagnosis of nafcillin-induced acute liver injury. Our case highlights the importance of early recognition of the diagnosis and careful monitoring of liver function when nafcillin is employed in the clinical setting.

scholarly journals Relationship between CYP2E1 Gene Polymorphism and Anti-tuberculosis Drug-induced Liver Injury

2018 ◽  
Vol 1 (4) ◽  
pp. 105
Author(s):  
Donglin Zhu ◽  
Yun Xi ◽  
Jieming Dong ◽  
Fanhua Huang ◽  
Changzhi Xu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Gene Polymorphism ◽  
Liver Damage ◽  
Gene Polymorphisms ◽  
Control Group ◽  
Case Group ◽  
Chinese Han ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Cyp2e1 Gene

 Objective: To investigate the relationship between cytochrome P450 E1 (CYP2E1) gene polymorphisms and susceptibility to anti-tuberculosis drug-induced liver damage (ATDLI) in tuberculosis patients in the Chinese Han nationality. Methods: A retrospective analysis was performed on 360 patients with tuberculosis who had liver damage after tuberculosis treatment (case group) and 360 patients with tuberculosis who did not develop liver injury after treatment (control group). MassARRAY were used to detect CYP2E1 gene polymorphisms. Results: In a total of 8 tagged SNP loci selected, the rs8192773 locus failed to pass the test, and therefore, it is not included in subsequent analysis. At the remaining seven SNP sites, the difference in alleles was not statistically significant between the case group and the control group, suggesting that these sites may not be related to liver damage caused by anti-tuberculosis drugs. Three monomer domains were found in the seven tags SNP loci mentioned above. However, it was found that these haplotypes are not closely related to anti-tuberculosis drug-induced liver damage. Conclusion: The CYP2E1 gene polymorphism in the Chinese Han nationality is not related to the occurrence of anti-tuberculosis drug-induced liver injury.

Current conservative treatment of uterine fibroids. Ulipristal acetate and liver damage: contrived tragedy?

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (6) ◽  
pp. 4-7
Author(s):  
A L Tikhomirov
Keyword(s):  
Risk Assessment ◽  
Liver Injury ◽  
Liver Damage ◽  
Uterine Fibroids ◽  
Tumor Formation ◽  
Drug Induced ◽  
Ulipristal Acetate ◽  
Drug Induced Liver Injury ◽  
Pharmacovigilance Risk Assessment Committee ◽  
Assessment Committee

Uterine fibroids are the most common pelvic tumor formation in women and the most common indication for hysterectomy. The effectiveness of long-term intermittent use of ulipristal acetate (UA) in patients with uterine myoma has been proven earlier. In May 2018, the ability of UA to cause a drug-induced liver injury (drug-induced liver injury, DILI) was disproved, and the European Commission approved a positive decision. According to the conclusion Expertise of the Pharmacovigilance Risk Assessment Committee (Pharmacovigilance Risk Assessment Committee - PRAC) the benefit/risk ratio remains favorable. Published recommendations are aimed at reducing the risk of liver damage. UA remains the 1st line of treatment for most myomas.

Prednisolone: role in amoxicillin–clavulanate-induced cholestatic liver injury

2021 ◽  
Vol 14 (4) ◽  
pp. e239488
Author(s):  
Melvin Qiyu Lee ◽  
Royale Chigozie ◽  
Irfan Khan ◽  
Gerard O'Mara
Keyword(s):  
Liver Injury ◽  
Liver Function Tests ◽  
Hepatocellular Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
The Us ◽  
Common Causes ◽  
Amoxicillin Clavulanate ◽  
The Common ◽  
Cholestatic Liver Injury

A 68-year-old patient presented with symptoms of a urinary tract infection. A deterioration in the patient’s liver function tests (LFTs) was noted 1 week following completion of a course of amoxicillin–clavunalate. This progressively worsened, reaching its peak by day 30. Our investigations excluded other possible causes for deranged LFTs and there was no improvement of same despite reduced dosing of potentially hepatotoxic medications.A trial of 30 mg/day prednisolone was commenced, resulting in an immediate and progressive improvement in LFTs to baseline over a period of 22 days and an improvement in constitutional symptoms such as tiredness and poor appetite. Drug-induced liver injury (DILI) is one of the common causes of acute hepatitis and a leading cause of acute liver failure in the US and Europe. Patterns of DILI can be generally divided into: (1) hepatocellular injury, (2) cholestatic injury and (3) mixed injury.

669 Chronic liver damage after an episode of idiosyncratic drug induced liver injury (DILI)

2006 ◽  
Vol 44 ◽  
pp. S247
Author(s):  
R.J. Andrade ◽  
M.I. Lucena ◽  
K. Pachkoria ◽  
Y. Borraz ◽  
N. Kaplowitz ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Damage ◽  
Chronic Liver ◽  
Drug Induced ◽  
Chronic Liver Damage ◽  
Drug Induced Liver Injury

scholarly journals Drug Induced Hepatotoxicity – An Ongoing Challenge

2020 ◽  
Vol 10 (3) ◽  
pp. 244-248
Author(s):  
Mehr Fatima ◽  
Syed Zaidi
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Liver Damage ◽  
Obese People ◽  
Drug Induced ◽  
Pharmacological Agents ◽  
Drug Induced Liver Injury ◽  
High Incidence ◽  
Inflammatory Drugs

Drug induced liver injury is one of the main factor of liver failure and acute liver damage world wide with high incidence in western countries. Liver injury can be intrinsic (dose dependant) or idiosyncratic (dose independent). However idiosyncratic type is considered to be mainly responsible for drug induced liver damage. Binding of reactive metabolites of drugs to tissue proteins and oxidative stress is the possible cellular mechanism involved in this process. Moreover, some antibiotics, anti-epileptics, nonsteroidal anti-inflammatory drugs etc are more likely to induce liver damage in high risks groups that includes females, elderly and obese people. HLA halotype and variation in protein expression also plays an important role in this context. Various studies are available regarding clinical features, histopathological features, diagnosis and management related to antibiotics and acetaminophen induced liver damage. N acetylcysteine is commonly available antidote for drug induced hepatic damage. Role of other pharmacological agents as an antidote requires further studies. However, liver transplantation should be considered with drug induced lethal liver failure

Ceftazidime induced liver injury

2021 ◽  
Vol 14 (12) ◽  
pp. e246571
Author(s):  
Tayyab Shah ◽  
James A Joslyn ◽  
James Lai
Keyword(s):  
Liver Injury ◽  
Type Ii Diabetes ◽  
Acute Liver Injury ◽  
Liver Function Tests ◽  
Type Ii Diabetes Mellitus ◽  
Rapid Identification ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Amoxicillin Clavulanate ◽  
Potential Hepatotoxicity

A 65-year-old woman with type II diabetes mellitus complicated by non-healing ulcers with recurrent osteomyelitis was admitted for progression of cellulitis after treatment failure with an outpatient course of amoxicillin-clavulanate. She was found to have persistent osteomyelitis and started on ceftazidime for a culture documented Pseudomonas aeruginosa infection. After two parenteral doses, she had a rapid rise in liver function tests (LFTs) in a hepatocellular pattern. Due to rapid identification, all medications with potential hepatotoxicity, including ceftazidime, were discontinued and the LFTs promptly returned to baseline over 3 days. Of note, the patient did not experience any symptoms of liver injury. Other causes of acute liver injury were effectively ruled out, but the case was confounded by usage of other potential hepatotoxic medications. Still, the most likely culprit was ceftazidime, a rare cause of drug induced liver injury with very few reports in the literature.

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