Evaluation of a Three-Dimensional Primary Human Hepatocyte Spheroid Model: Adoption and Industrialization for the Enhanced Detection of Drug-Induced Liver Injury

2021 ◽  
Author(s):  
Christopher A. Schofield ◽  
Tracy M. Walker ◽  
Maxine A. Taylor ◽  
Metul Patel ◽  
Denise F. Vlachou ◽  
...  
Keyword(s):  
Liver Injury ◽  
Three Dimensional ◽  
Human Hepatocyte ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Hepatocyte Spheroid ◽  
Primary Human Hepatocyte

scholarly journals Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Catherine C. Bell ◽  
Delilah F. G. Hendriks ◽  
Sabrina M. L. Moro ◽  
Ewa Ellis ◽  
Joanne Walsh ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Model System ◽  
Human Hepatocyte ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Primary Human Hepatocyte ◽  
Hepatocyte Spheroids

scholarly journals Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals

2021 ◽  
Vol 22 (20) ◽  
pp. 11005
Author(s):  
Vânia Vilas-Boas ◽  
Eva Gijbels ◽  
Kaat Leroy ◽  
Alanah Pieters ◽  
Audrey Baze ◽  
...  
Keyword(s):  
Cyclosporine A ◽  
Prolonged Exposure ◽  
Human Hepatocyte ◽  
Drug Induced ◽  
Clinical Issue ◽  
Drug Induced Liver Injury ◽  
Primary Human Hepatocyte ◽  
Donor Variability ◽  
Hepatocyte Spheroids

Drug-induced liver injury, including cholestasis, is an important clinical issue and economic burden for pharmaceutical industry and healthcare systems. However, human-relevant in vitro information on the ability of other types of chemicals to induce cholestatic hepatotoxicity is lacking. This work aimed at investigating the cholestatic potential of non-pharmaceutical chemicals using primary human hepatocytes cultured in 3D spheroids. Spheroid cultures were repeatedly (co-) exposed to drugs (cyclosporine-A, bosentan, macitentan) or non-pharmaceutical chemicals (paraquat, tartrazine, triclosan) and a concentrated mixture of bile acids for 4 weeks. Cell viability (adenosine triphosphate content) was checked every week and used to calculate the cholestatic index, an indicator of cholestatic liability. Microarray analysis was performed at specific time-points to verify the deregulation of genes related to cholestasis, steatosis and fibrosis. Despite the evident inter-donor variability, shorter exposures to cyclosporine-A consistently produced cholestatic index values below 0.80 with transcriptomic data partially supporting its cholestatic burden. Bosentan confirmed to be hepatotoxic, while macitentan was not toxic in the tested concentrations. Prolonged exposure to paraquat suggested fibrotic potential, while triclosan markedly deregulated genes involved in different types of hepatotoxicity. These results support the applicability of primary human hepatocyte spheroids to study hepatotoxicity of non-pharmaceutical chemicals in vitro.

Leberschaden unter oraler Antikoagulation, Statin- und ACE-Hemmertherapie

Praxis ◽  
2010 ◽  
Vol 99 (21) ◽  
pp. 1259-1265 ◽  
Author(s):  
Bruggisser ◽  
Terraciano ◽  
Rätz Bravo ◽  
Haschke
Keyword(s):  
Liver Injury ◽  
Wird Eine ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Ein 71-jähriger Patient stellt sich mit Epistaxis und ikterischen Skleren auf der Notfallstation vor. Der Patient steht unter einer Therapie mit Phenprocoumon, Atorvastatin und Perindopril. Anamnestisch besteht ein langjähriger Alkoholabusus. Laborchemisch werden massiv erhöhte Leberwerte (ALAT, Bilirubin) gesehen. Der INR ist unter oraler Antikoagulation und bei akuter Leberinsuffizienz >12. Die weiterführenden Abklärungen schliessen eine Virushepatitis und eine Autoimmunhepatitis aus. Nachdem eine Leberbiopsie durchgeführt werden kann, wird eine medikamentös-toxische Hepatitis, ausgelöst durch die Komedikation von Atorvastatin, Phenprocoumon und Perindopril bei durch Alkohol bereits vorgeschädigter Leber diagnostiziert. Epidemiologie, Pathophysiologie und Klink der medikamentös induzierten Leberschäden (drug induced liver injury, DILI), speziell von Coumarinen, Statinen und ACE-Hemmern werden im Anschluss an den Fallbericht diskutiert.

Drug-induced liver injury network (DILIN)

Hepatology ◽  
2004 ◽  
Vol 40 (4) ◽  
pp. 773-773 ◽  
Author(s):  
Jay H. Hoofnagle
Keyword(s):  
Liver Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Drug induced liver injury associated with Flupirtine in 6 cases

2011 ◽  
Vol 49 (08) ◽  
Author(s):  
C Agne ◽  
K Rifai ◽  
HH Kreipe ◽  
MP Manns ◽  
F Puls
Keyword(s):  
Liver Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury

WISP1 modulates immune cell infiltration upon drug-induced liver injury (DILI)

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
AB Widera ◽  
L Pütter ◽  
S Leserer ◽  
G Campos ◽  
K Rochlitz ◽  
...  
Keyword(s):  
Liver Injury ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Drug Induced ◽  
Drug Induced Liver Injury
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