Article
Gastroenterology & Hepatology
Robert J. Fontana, Einar S. Bjornsson, Rajender Reddy, Raul J. Andrade
Summary: Idiosyncratic drug-induced liver injury (DILI) is a rare but significant cause of liver disease. Newly identified causes of DILI include COVID vaccines, turmeric, green tea extract, and immune checkpoint inhibitors. DILI is diagnosed through exclusion, requiring evaluation for more common causes and a temporal association with the suspected drug. Advances in DILI causality assessment and drug-specific HLA associations have improved diagnosis and prognosis. LiverTox provides important information on the hepatotoxicity profile of medications and supplements.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Estela Villanueva-Badenas, M. Teresa Donato, Laia Tolosa
Summary: Hepatotoxicity or drug-induced liver injury (DILI) is a significant problem in drug development, leading to drug failure and regulatory measures. The development of a co-culture system involving hepatocytes and other cell types has been shown to enhance the understanding and prediction of iDILI. In this study, a co-culture system using HepG2 cells and THP-1-derived macrophages was established and used to evaluate the effects of model iDILI compounds on viability and oxidative stress induction.
Review
Pharmacology & Pharmacy
Mercedes Robles-Diaz, Lana Nezic, Vesna Vujic-Aleksic, Einar S. Bjornsson
Summary: UDCA may have some benefits in the treatment and prevention of DILI according to available data, but a well designed RCT is needed to draw a firm conclusion on its efficacy in DILI.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Edmond Atallah, Cristiana Freixo, Ismael Alvarez-Alvarez, F. J. Cubero, Alexander L. Gerbes, Gerd A. Kullak-Ublick, Guruprasad P. Aithal
Summary: This systematic review presents the available evidence for biomarkers in the diagnosis or prognosis of DILI, highlighting the heterogeneity in diagnostic studies and the improved prognostic ability when integrating novel and traditional biomarkers in prognostic models.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2021)
Review
Cell Biology
Sydney Stern, Hongbing Wang, Nakissa Sadrieh
Summary: Drug-induced liver injury (DILI) is a major concern in the pharmaceutical industry and global health due to its high attrition rates and complex pathogenesis. In vitro co-culture models that incorporate the immune system have shown promise in investigating idiosyncratic DILI (iDILI). Human-based 3D multicellular models have been developed to mimic the hepatic microenvironment and provide a more accurate representation of iDILI. However, more research is needed to harmonize and compare the characteristics of these models, as well as address challenges such as disease-related endpoints and multi-cellular mechanisms.
Article
Pharmacology & Pharmacy
Binbin Lv, Longshan Liu, Xiaoman Liu, Min Huang, Xiao Chen, Kejing Tang, Changxi Wang, Pan Chen
Summary: In this study, the occurrence of tacrolimus-induced liver injury (tac-DILI) in renal transplant recipients was investigated. The most common type of tac-DILI was found to be the cholestatic pattern. Baseline ALP level, age, and body weight were identified as independent risk factors.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Bernd Rattay, Ralf A. Benndorf
Summary: Drug-induced agranulocytosis is a life-threatening side effect that can be triggered by various drugs, characterized by idiosyncratic reactions and a low incidence rate. It is thought to be initiated by chemically reactive drugs or metabolites that elicit an immune response, affecting cells or organs with specific metabolic activities.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Gastroenterology & Hepatology
Amoah Yeboah-Korang, Ahmed Memon, Neil Patel, Andrea Portocarrero-Castillo, Askanda Osman, David Kleesattel, Carmen Lopez, Jeremy Louissaint, Kenneth Sherman, Robert Fontana
Summary: This study compared the frequency, clinical features, and outcomes of drug-induced liver injury (DILI) in patients with and without a history of prior drug allergy. The results showed that a prior drug allergy history was not associated with a greater likelihood of developing DILI, but DILI patients with a history of prior drug allergy tended to have less severe liver injury and clinical outcomes. Additionally, the low rate of suspect drug documentation after a DILI episode is of concern and could lead to avoidable harm from inadvertent suspect drug re-challenge.
DIGESTIVE DISEASES AND SCIENCES
(2022)
Article
Cell Biology
Yuan Gao, Guang Xu, Li Ma, Wei Shi, Zhilei Wang, Xiaoyan Zhan, Nan Qin, Tingting He, Yuming Guo, Ming Niu, Jiabo Wang, Zhaofang Bai, Xiaohe Xiao
Summary: The study revealed that Icariside I specifically facilitates ATP- or nigericin-induced NLRP3 inflammasome activation and leads to idiosyncratic hepatotoxicity. It is suggested to avoid using Icariside I or EF in patients with diseases related to ATP- or nigericin-induced NLRP3 inflammasome activation, which may be risk factors for idiosyncratic drug-induced liver injury (IDILI).
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Oncology
Nan Qin, Guang Xu, Yan Wang, Xiaoyan Zhan, Yuan Gao, Zhilei Wang, Shubin Fu, Wei Shi, Xiaorong Hou, Chunyu Wang, Ruisheng Li, Yan Liu, Jiabo Wang, Haiping Zhao, Xiaohe Xiao, Zhaofang Bai
Summary: Bavachin isolated from Psoraleae Fructus enhances the specific stimuli-induced activation of the NLRP3 inflammasome, leading to hepatotoxicity.
FRONTIERS OF MEDICINE
(2021)
Article
Toxicology
Fernando Bessone, Antonella Ferrari, Nelia Hernandez, Manuel Mendizabal, Ezequiel Ridruejo, Alina Zerega, Federico Tanno, Maria Virginia Reggiardo, Julio Vorobioff, Hugo Tanno, Marco Arrese, Vinicius Nunes, Martin Tagle, Inmaculada Medina-Caliz, Mercedes Robles-Diaz, Hao Niu, Ismael Alvarez-Alvarez, Camilla Stephens, M. Isabel Lucena, Raul J. Andrade
Summary: In this study, the demographics, clinical characteristics, biochemical features, and outcome of nitrofurantoin-induced liver injury were described. The majority of the cases were women with a mean age of 61 years. Hepatocellular damage was the most common pattern of liver injury, and about half of the patients were asymptomatic. Most patients recovered within six months, but a small number developed nitrofurantoin-induced autoimmune-like hepatitis.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Gastroenterology & Hepatology
Jeremy Louissaint, Ihab Kassab, Amoah Yeboah-Korang, Robert J. Fontana
Summary: Combining K72 codes with drug poisoning T-codes had limited utility in identifying patients with idiosyncratic DILI, but still showed some diagnostic value, supporting further refinement of algorithms for detecting DILI cases in the EMR.
DIGESTIVE DISEASES AND SCIENCES
(2022)
Article
Spectroscopy
Zhao Wang, Fan Zhang, Jianhua Xiong, Zhiqiang Mao, Zhihong Liu
Summary: This study developed a two-photon fluorescence probe for peroxynitrite, which can sensitively image ONOO- in mouse liver and demonstrate the potential application in DILI screening.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2021)
Article
Chemistry, Analytical
Guo-Jiang Mao, Guang-Qi Gao, Wen-Pei Dong, Qian-Qian Wang, Ying-Ying Wang, Yao Li, Li Su, Guisheng Zhang
Summary: In this study, a two-photon excited near-infrared fluorescence probe (NIR-ONOO-) was developed for the detection and imaging of peroxynitrite (ONOO-), which is an important biomarker for drug-induced liver injury and other drug-induced damage. NIR-ONOO showed high selectivity, sensitivity, and performance for ONOO- detection, making it a powerful chemical tool for imaging ONOO- and assessing drug-induced hepatotoxicity.
Review
Cell Biology
Silvia Bressan, Alessandra Pierantoni, Saman Sharifi, Sergio Facchini, Vincenzo Quagliarello, Massimiliano Berretta, Monica Montopoli
Summary: HIV patients have increased risk of developing cancer and treating those with both HIV and cancer can be complicated due to the risk of drug-drug interactions. Temporary discontinuation of ART may be a strategy to manage the risk of DDIs.