Assessment of Serious Acute and Chronic Idiosyncratic Drug-Induced Liver Injury in Clinical Practice

2019 ◽  
Vol 39 (03) ◽  
pp. 381-394 ◽  
Author(s):  
Fernando Bessone ◽  
Mercedes Robles-Diaz ◽  
Nelia Hernandez ◽  
Inmaculada Medina-Caliz ◽  
M. Isabel Lucena ◽  
...  

AbstractDrug-induced liver injury (DILI) is the leading cause of acute liver failure (ALF) in developed countries. The extremely variable phenotype of DILI, both in presentation and in severity, is one of the distinctive characteristics of the disease and one of the major challenges that hepatologists face when assessing hepatotoxicity cases. A new Hy's law that more accurately predicts the risk of ALF related to DILI has been proposed and validated. Other prognostic scoring algorithms for the early identification of DILI patients who may go on to develop ALF have been developed as it is of most clinical relevance to stratify patients for closer monitoring. Recent data indicate that acute DILI often presents a more prolonged resolution or evolves into chronicity at a higher frequency than other forms of acute liver injury. Risk factors for chronicity, specific phenotypes, and histological features are discussed in this study. Biomarkers to predict DILI outcome are in need.

2020 ◽  
Vol 20 (2) ◽  
pp. 125-138 ◽  
Author(s):  
Bharat Bhushan ◽  
Udayan Apte

Acetaminophen (APAP) overdose is the major cause of acute liver failure (ALF) in the Western world. Extensive research is ongoing to identify the mechanisms of APAP-induced ALF. APAP-induced acute liver injury is also one of the most commonly studied drug-induced liver injury models in the field of hepatotoxicity. APAP toxicity is triphasic and includes three mechanistically interlinked but temporally distinct phases of initiation, progression, and recovery/regeneration. Despite how commonly it is studied, the methods to study APAP toxicity differ significantly, often leading to confusing and contradictory data. There are number of reviews on mechanisms of APAP toxicity, but a detailed mechanism-based comprehensive method and list of assays that covers all phases of APAP hepatotoxicity are missing. The goal of this review is to provide a standard protocol and guidelines to study APAP toxicity in mice including a test battery that can help investigators to comprehensively analyze APAP toxicity in the specific context of their hypothesis. Further, we will identify the major roadblocks and common technical problems that can significantly affect the results. This acetaminophen test battery (ATB) will be an excellent guide for scientists studying this most common and clinically relevant drug-induced liver injury and will also be helpful as a roadmap for hypothesis development to study novel mechanisms.


Drug Safety ◽  
2013 ◽  
Vol 37 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Xin Shen ◽  
Zheng’an Yuan ◽  
Jian Mei ◽  
Zurong Zhang ◽  
Juntao Guo ◽  
...  

2020 ◽  
Vol 33 (7) ◽  
pp. 1551-1560 ◽  
Author(s):  
Markus Walles ◽  
Alan P. Brown ◽  
Alfred Zimmerlin ◽  
Peter End

2017 ◽  
Vol 11 (3) ◽  
pp. 564-568 ◽  
Author(s):  
Qin Rao ◽  
Isaiah Schuster ◽  
Talal Seoud ◽  
Kevin Zarrabi ◽  
Nirvani Goolsarran

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.


2013 ◽  
Vol 35 (8) ◽  
pp. e25
Author(s):  
M. Robles-Díaz ◽  
C. Stephens ◽  
I. Medina-Cáliz ◽  
A.F. González ◽  
A. González-Jiménez ◽  
...  

Author(s):  
Diogo Costa Santos ◽  
Graça Lérias ◽  
Isabel Madruga

Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the Western world. In recent years, natural herbal and dietary supplements have become widely available to the general public and have increased in popularity. Reports of idiosyncratic liver injury caused by such supplements have also increased over the last decade. Horse chestnut is a herb used in dietary supplements primarily for complications of venous insufficiency. Clinically significant acute liver injury has been very rarely associated with its use. We present the case of a 70-year-old man with idiosyncratic horse chestnut-induced liver injury.


PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0212394 ◽  
Author(s):  
Herbert L. Bonkovsky ◽  
Huiman X. Barnhart ◽  
David M. Foureau ◽  
Nury Steuerwald ◽  
William M. Lee ◽  
...  

2020 ◽  
Vol 94 (9) ◽  
pp. 3185-3200
Author(s):  
Leah M. Norona ◽  
Aaron Fullerton ◽  
Chris Lawson ◽  
Leslie Leung ◽  
Jochen Brumm ◽  
...  

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