scholarly journals Olaparib-Induced Immune-Mediated Liver Injury

2022 ◽  
Vol 9 (1) ◽  
pp. e00735
Author(s):  
Mohammad Alshelleh ◽  
Jennifer Park ◽  
Veena John ◽  
Arvind Rishi ◽  
David Bernstein ◽  
...  
Keyword(s):  
Liver Injury ◽  
Immune Mediated

scholarly journals Investigating the Mechanism of Trimethoprim-Induced Skin Rash and Liver Injury

2021 ◽  
Author(s):  
Yanshan Cao ◽  
Ahsan Bairam ◽  
Alison Jee ◽  
Ming Liu ◽  
Jack Uetrecht
Keyword(s):  
Liver Injury ◽  
Skin Rash ◽  
Covalent Binding ◽  
Reactive Metabolites ◽  
Important Data ◽  
Drug Induced ◽  
Interindividual Differences ◽  
Immune Mediated ◽  
Sulfate Conjugate

Abstract Trimethoprim (TMP)-induced skin rash and liver injury are likely to involve the formation of reactive metabolites. Analogous to nevirapine-induced skin rash, one possible reactive metabolite is the sulfate conjugate of α-hydroxyTMP, a metabolite of TMP. We synthesized this sulfate and found that it reacts with proteins in vitro. We produced a TMP-antiserum and found covalent binding of TMP in the liver of TMP-treated rats. However, we found that α-hydroxyTMP is not a substrate for human sulfotransferases, and we did not detect covalent binding in the skin of TMP-treated rats. Although less reactive than the sulfate, α-hydroxyTMP was found to covalently bind to liver and skin proteins in vitro. Even though there was covalent binding to liver proteins, TMP did not cause liver injury in rats or in our impaired immune tolerance mouse model that has been able to unmask the ability of other drugs to cause immune-mediated liver injury. This is likely because there was much less covalent binding of TMP in the livers of TMP-treated mice than TMP-treated rats. It is possible that some patients have a sulfotransferase that can produce the reactive benzylic sulfate; however, α-hydroxyTMP, itself, has sufficient reactivity to covalently bind to proteins in the skin and may be responsible for TMP-induced skin rash. Interspecies and interindividual differences in TMP metabolism may be one factor that determines the risk of TMP-induced skin rash. This study provides important data required to understand the mechanism of TMP-induced skin rash and drug-induced skin rash in general.

scholarly journals Immune-Mediated Drug-Induced Liver Injury: Immunogenetics and Experimental Models

2021 ◽  
Vol 22 (9) ◽  
pp. 4557
Author(s):  
Alessio Gerussi ◽  
Ambra Natalini ◽  
Fabrizio Antonangeli ◽  
Clara Mancuso ◽  
Elisa Agostinetto ◽  
...  
Keyword(s):  
Liver Injury ◽  
Experimental Models ◽  
Clinical Event ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Immune Mediated ◽  
Liver Injuries ◽  
Immunological Mechanisms ◽  
Molecular Aspects ◽  
Therapeutic Tools

Drug-induced liver injury (DILI) is a challenging clinical event in medicine, particularly because of its ability to present with a variety of phenotypes including that of autoimmune hepatitis or other immune mediated liver injuries. Limited diagnostic and therapeutic tools are available, mostly because its pathogenesis has remained poorly understood for decades. The recent scientific and technological advancements in genomics and immunology are paving the way for a better understanding of the molecular aspects of DILI. This review provides an updated overview of the genetic predisposition and immunological mechanisms behind the pathogenesis of DILI and presents the state-of-the-art experimental models to study DILI at the pre-clinical level.

scholarly journals Mesenchymal stem cells alleviate experimental immune-mediated liver injury via chitinase 3-like protein 1-mediated T cell suppression

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Qiuli Liu ◽  
Xiaoyong Chen ◽  
Chang Liu ◽  
Lijie Pan ◽  
Xinmei Kang ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Liver Injury ◽  
T Cell Activation ◽  
Gene Set Enrichment Analysis ◽  
Human Umbilical Cord ◽  
Con A ◽  
Immune Mediated

AbstractLiver diseases with different pathogenesis share common pathways of immune-mediated injury. Chitinase-3-like protein 1 (CHI3L1) was induced in both acute and chronic liver injuries, and recent studies reported that it possesses an immunosuppressive ability. CHI3L1 was also expressed in mesenchymal stem cells (MSCs), thus we investigates the role of CHI3L1 in MSC-based therapy for immune-mediated liver injury here. We found that CHI3L1 was highly expressed in human umbilical cord MSCs (hUC-MSCs). Downregulating CHI3L1 mitigated the ability of hUC-MSCs to inhibit T cell activation, proliferation and inflammatory cytokine secretion in vitro. Using Concanavalin A (Con A)-induced liver injury mouse model, we found that silencing CHI3L1 significantly abrogated the hUC-MSCs-mediated alleviation of liver injury, accompanying by weakened suppressive effects on infiltration and activation of hepatic T cells, and secretion of pro-inflammatory cytokines. In addition, recombinant CHI3L1 (rCHI3L1) administration inhibited the proliferation and function of activated T cells, and alleviated the Con A-induced liver injury in mice. Mechanistically, gene set enrichment analysis showed that JAK/STAT signalling pathway was one of the most significantly enriched gene pathways in T cells co-cultured with hUC-MSCs with CHI3L1 knockdown, and further study revealed that CHI3L1 secreted by hUC-MSCs inhibited the STAT1/3 signalling in T cells by upregulating peroxisome proliferator-activated receptor δ (PPARδ). Collectively, our data showed that CHI3L1 was a novel MSC-secreted immunosuppressive factor and provided new insights into therapeutic treatment of immune-mediated liver injury.

Immune-mediated liver injury

2005 ◽  
Vol 42 (6) ◽  
pp. 920-923 ◽  
Author(s):  
Johannes Herkel ◽  
Marcus Schuchmann ◽  
Gisa Tiegs ◽  
Ansgar W. Lohse
Keyword(s):  
Liver Injury ◽  
Immune Mediated

Biopsy Pathology and Immunohistochemistry of a Case of Immune‐Mediated Drug‐Induced Liver Injury With Atabecestat

Hepatology ◽  
2020 ◽  
Author(s):  
Sandra De Jonghe ◽  
Daniel Weinstock ◽  
Jason Aligo ◽  
Kay Washington ◽  
Dean Naisbitt
Keyword(s):  
Liver Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Immune Mediated

scholarly journals Natural killer T cells play a necessary role in modulating of immune-mediated liver injury by gut microbiota

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Jianing Chen ◽  
Yingfeng Wei ◽  
Jianqin He ◽  
Guangying Cui ◽  
Yunan Zhu ◽  
...  
Keyword(s):  
T Cells ◽  
Liver Injury ◽  
Gut Microbiota ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
Immune Mediated ◽  
Killer T Cells ◽  
Natural Killer T

scholarly journals Cooperative effect of biliverdin and carbon monoxide on survival of mice in immune-mediated liver injury

Hepatology ◽  
2004 ◽  
Vol 40 (5) ◽  
pp. 1128-1135 ◽  
Author(s):  
Gabriele Sass ◽  
Stefan Seyfried ◽  
Miguel Parreira Soares ◽  
Kenichiro Yamashita ◽  
Elzbieta Kaczmarek ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Liver Injury ◽  
Cooperative Effect ◽  
Immune Mediated

scholarly journals Liver Injury with Features Mimicking Autoimmune Hepatitis following the Use of Black Cohosh

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Grace Guzman ◽  
Eric R. Kallwitz ◽  
Christina Wojewoda ◽  
Rohini Chennuri ◽  
Jamie Berkes ◽  
...  
Keyword(s):  
Liver Injury ◽  
Autoimmune Hepatitis ◽  
Plasma Cells ◽  
Hepatic Necrosis ◽  
Serum Markers ◽  
Black Cohosh ◽  
Herbal Supplement ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Immune Mediated

There are a growing number of cases detailing acute hepatic necrosis in patients taking black cohosh (Cimicifuga racemosa), an over-the-counter herbal supplement for management of menopausal symptoms. Our aim is to illustrate two cases of liver injury following the use of black cohosh characterized by histopathological features mimicking autoimmune hepatitis. Both patients reported black cohosh use for at least six months and had no evidence of another cause of liver disease. Their liver biopsies showed a component of centrilobular necrosis consistent with severe drug-induced liver injury. In addition, the biopsies showed characteristics of autoimmune-like liver injury with an interface hepatitis dominated by plasma cells. Although serum markers for autoimmune hepatitis were not particularly elevated, both patients responded to corticosteroids, supporting an immune-mediated component to the liver injury. Liver injury following the use of black cohosh should be included in the list of differential diagnoses for chronic hepatitis with features mimicking autoimmune hepatitis.

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