Review
Biochemistry & Molecular Biology
Rolf Teschke, Gaby Danan
Summary: Progress has been made in understanding the mechanisms of idiosyncratic drug-induced liver injury (iDILI) worldwide, with the identification of metabolic risk factors. However, uncertainty remains regarding the prediction of iDILI, with controversies surrounding certain risks factors such as drug doses and hepatic drug metabolism. Further research is needed to address these methodological flaws and establish stronger evidence for risk factors of iDILI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Alison Jee, Samantha Christine Sernoskie, Jack Uetrecht
Summary: IDILI remains a significant problem for patients and drug development due to its idiosyncratic nature. Most cases of IDILI are likely caused by reactive metabolites of drugs and mediated by the adaptive immune system, with some associations with specific human leukocyte antigen haplotypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
Mengmeng Lin, Yingying Li, Bo Cao, Jing Xu, Yujun Zhang, Guohui Li, Xiaohe Xiao, Chunyu Li
Summary: This study found that bavachin and epimedin B caused significant liver injury under immunological stress conditions, and resulted in differential gene expression related to liver metabolism and immune system processes. The combination of bavachin and epimedin B not only affected immune system processes, but also lipid metabolism, leading to an imbalance in the immune microenvironment in the liver.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Immunology
Yan Wang, Guang Xu, Zhilei Wang, Ruisheng Li, Xiaoyan Zhan, Hongbin Liu, Qin Qin, Weixia Li, Xiaoyan Wang, Mingliang Zhang, Jinfa Tang, Zhaofang Bai, Xiaohe Xiao
Summary: This study found that psoralidin from Psoraleae Fructus induces idiosyncratic drug-induced liver injury (IDILI) by activating inflammasomes. The results suggest that psoralidin can activate not only the NLRP3 inflammasome but also other types of inflammasomes. The study further revealed the mechanism of liver injury induced by psoralidin.
INTERNATIONAL IMMUNOPHARMACOLOGY
(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)
Article
Immunology
Hyun Yang, Ji Won Han, Jae Jun Lee, Ahlim Lee, Sung Woo Cho, Pu Reun Rho, Min-Woo Kang, Jeong Won Jang, Eun Sun Jung, Jong Young Choi, Pil Soo Sung, Si Hyun Bae
Summary: This study investigated the phenotypes and clinical implications of liver-infiltrating immune cells in idiosyncratic drug-induced liver injury (DILI). The results showed that activated CD8+ T cells and mononuclear phagocytes are associated with drug-induced liver injury. Therefore, steroids are suggested as a potential treatment option for idiosyncratic DILI.
FRONTIERS IN IMMUNOLOGY
(2023)
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)
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
Gastroenterology & Hepatology
Jieting Tang, Jin Gu, Naihui Chu, Yu Chen, Yongliang Wang, Dongying Xue, Qing Xie, Lei Li, Zaoxian Mei, Xiaojin Wang, Jun Li, Jun Chen, Yi Li, Changqing Yang, Yingxin Wang, Jia Shang, Wen Xie, Peng Hu, Dongliang Li, Limin Zhao, Pei Lan, Chen Wang, Chengwei Chen, Yimin Mao
Summary: This study investigated the efficacy and safety of bicyclol in acute drug-induced liver injury. The results showed that bicyclol reduced ALT levels and improved ALT normalization rates, with no significant difference in safety compared to the control group.
LIVER INTERNATIONAL
(2022)
Review
Environmental Sciences
Rebecca Allison, Asha Guraka, Isaac Thom Shawa, Gyan Tripathi, Wolfgang Moritz, Ali Kermanizadeh
Summary: This review primarily focuses on the mechanisms, risk factors, and the impact of the coronavirus pandemic on idiosyncratic drug-induced liver injury (DILI). Although some molecular mechanisms are known, the underlying mechanisms responsible for DILI are still unknown. Prevention strategies are crucial due to limited treatment options once the injury has occurred.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS
(2023)
Review
Biochemistry & Molecular Biology
Camilla Stephens, M. Isabel Lucena, Raul J. Andrade
Summary: Idiosyncratic drug-induced liver injury (DILI) is a challenging condition with genetic predispositions believed to contribute to susceptibility. Genetic studies have identified various polymorphisms associated with DILI susceptibility, but not all have been confirmed in independent studies. Genome-wide significant associations between HLA risk alleles and DILI due to specific causative agents support the hypothesis that DILI is partially immune-mediated, aiding in diagnosis and clinical decision-making.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2021)
Review
Immunology
Yan-zhong Han, Zhi-tao Ma, Ming-xi Zhou, Ming Niu, Xu Zhao, Yu-ming Guo, Xin-hua Song, Ya-wen Lu, Zhao-fang Bai, Zhen Li, Han Gao, Yong-kang Zhao, Jia-bo Wang, Xiao-he Xiao, Jing Jing
Summary: By using metabolomics analysis, it has been found that drug-induced liver injury with autoantibodies may not be a homogeneous group in terms of pathogenesis, including a subset with autoimmune hepatitis tendencies. This finding calls for further investigation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
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.
Review
Biochemistry & Molecular Biology
Rolf Teschke
Summary: Drug induced liver injury (DILI) occurs in patients exposed to drugs at recommended doses and provides an excellent human model with well described clinical features, liver injury pattern, and diagnostic criteria. Direct evidence from cases assessed using RUCAM shows the involvement of the immune system and genetic HLA genotypes in DILI. The identification of immune mechanisms and genetics in DILI may contribute to understanding the disease and developing new approaches for therapy and prevention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
