Incidence, characteristics and risk factors for drug‐induced liver injury in hospitalized patients: A matched case‐control study

Kong, Xiangru; Guo, Dai-Hong; Liu, Siyuan; Zhu, Yu; Yu, Chengxuan

doi:10.1111/bcp.14847

Cited by 15 publications

(3 citation statements)

References 30 publications

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“…The improper use of health products, such as prescription medicines, over-the-counter drugs and traditional Chinese medicines, can cause varying degrees of liver damage ( 27 ). The incidence of drug-induced liver injury (DILI) has been increasing in recent years ( 28 ). In the process of DILI, drugs and their metabolites combine with endogenous hepatocyte components to form new complexes, which activate hepatocytes and lead to hepatocyte injury or even death ( 29 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway

Kang

Pan

et al. 2022

Int J Mol Med

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As the current clinical treatment of acetaminophen (APAP)-induced liver injury (AILI) has its limitations, new and effective treatment methods are required. Fingolimod (FTY720) is an immunosuppressive drug developed in recent years that has been shown to have a protective effect against ischemia/reperfusion liver injury. However, the role of FTY720 in AILI remains unclear. The aim of the present study was to determine whether FTY720 has a protective effect on AILI. AILI was induced using intraperitoneal injection of 300 mg/kg APAP in male C57BL/6J mice. Following APAP challenge, the mice were administered 5 mg/kg FTY720 for 30 min. Protein expression levels were measured using western blot analysis. Cell viability was examined using Cell Counting Kit-8 assays. mRNA levels were measured using reverse transcription-quantitative PCR. Inflammation levels were evaluated using immunohistochemistry. Cell death and reactive oxygen species levels were examined using immunofluorescence. Furthermore, laser scanning intravital microscopy was used to directly observe immune cell recruitment. APAP treatment increased the serum levels of alanine transaminase and aspartate transaminase at the 6- and 12-h time-points, suggesting liver tissue damage. However, FTY720 attenuated the liver injury induced by APAP by reducing the recruitment of immune cells and the release of pro-inflammatory cytokines and chemokines. FTY720 activated JAK2/STAT3 signaling and regulated the expression of BAX, BCL-2 and p65 to inhibit apoptosis and inflammation. In addition, compared with APAP treatment, the viability of primary hepatocytes treated with APAP and FTY720 was increased. Inhibition of JAK2/STAT3 signaling attenuated the protective, antioxidant effects of FTY720. In conclusion, FTY720 reduced liver injury by regulating the JAK2/STAT3 signaling pathway. This compound was capable of inhibiting oxidative stress to reduce hepatocyte death and the infiltration of neutrophils in the liver.

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Section: Discussionmentioning

confidence: 99%

FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway

Kang

Pan

et al. 2022

Int J Mol Med

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“…According to the clinical RUCAM evaluation, the incidence of liver toxicity ranges from 1.33% to 34.3% (Table 2). [20][21][22][23][24][25] Hence, identifying strategies to reduce VRCinduced hepatotoxicity has clinical significance.…”

Section: Published Clinical Evaluation Of Vrc-induced Hepatotoxicity ...mentioning

confidence: 99%

Astragalus Polysaccharide Enhances Voriconazole Metabolism under Inflammatory Conditions through the Gut Microbiota

Wang,

Hu,

et al. 2024

J Clin Transl Hepatol

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Background and Aims Voriconazole (VRC), a widely used antifungal drug, often causes hepatotoxicity, which presents a significant clinical challenge. Previous studies demonstrated that Astragalus polysaccharide (APS) can regulate VRC metabolism, thereby potentially mitigating its hepatotoxic effects. In this study, we aimed to explore the mechanism by which APS regulates VRC metabolism. Methods First, we assessed the association of abnormal VRC metabolism with hepatotoxicity using the Roussel Uclaf Causality Assessment Method scale. Second, we conducted a series of basic experiments to verify the promotive effect of APS on VRC metabolism. Various in vitro and in vivo assays, including cytokine profiling, immunohistochemistry, quantitative polymerase chain reaction, metabolite analysis, and drug concentration measurements, were performed using a lipopolysaccharide-induced rat inflammation model. Finally, experiments such as intestinal biodiversity analysis, intestinal clearance assessments, and Bifidobacterium bifidum replenishment were performed to examine the ability of B. bifidum to regulate the expression of the VRC-metabolizing enzyme CYP2C19 through the gut–liver axis. Results The results indicated that APS does not have a direct effect on hepatocytes. However, the assessment of gut microbiota function revealed that APS significantly increases the abundance of B. bifidum , which could lead to an anti-inflammatory response in the liver and indirectly enhance VRC metabolism. The dual-luciferase reporter gene assay revealed that APS can hinder the secretion of pro-inflammatory mediators and reduce the inhibitory effect on CYP2C19 transcription through the nuclear factor-κB signaling pathway. Conclusions The study offers valuable insights into the mechanism by which APS alleviates VRC-induced liver damage, highlighting its immunomodulatory influence on hepatic tissues and its indirect regulatory control of VRC-metabolizing enzymes within hepatocytes.

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“…Currently, the internationally recognised incidence of DILI is 19.1/100,000 and 13.9/100,000 people (Dominique, 2002;Björnsson et al, 2013). However, the incidence of DILI/HILI in China is still unclear, and two recent studies (retrospective observation) with large sample sizes estimated the incidence of DILI in China to be 23.8/100,000 and 320/100,000 people respectively, which is higher than that in the West (Shen et al, 2019;Kong et al, 2021). The incidence of HILI was calculated as the number of people who took herbs and developed HILI thereafter.…”

Section: Pharmacoepidemiology 21 Incidence and Prevalence Of Herbindu...mentioning

confidence: 99%

A review of herb-induced liver injury in mainland china

Yang

Tang

et al. 2022

Front. Pharmacol.

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Traditional medicines have greatly contributed to people’s health worldwide. However, in recent years, the frequent occurrence of herb-induced liver injury (HILI) has raised public concerns regarding the safety of herbs. HILI not only severely impacts public health, thus increasing its medical burden, but also consumes medical resources. However, the pharmacoepidemiology and risk factors of HILI are still unclear due to the complexity of herbs (medication theory, drug composition, dual properties of drugs and food, etc.). China is the country with the most extensive use of herbs and cases of HILI worldwide. The safety profile of herbs (especially with respect to HILI) has also affected the use of herbs internationally. Therefore, this review focuses on the epidemic situation of HILI in mainland China to compile its characteristics, while focusing on the three main aspects of patients, drugs, and unreasonable prescriptions to explore the potential risk factors. Our objective was to provide a reference for HILI pharmacovigilance and risk prevention and control and contribute to Chinese knowledge of the realisation of the “Medication without Harm” global safe medication strategic goal of the World Health Organization.

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Incidence, characteristics and risk factors for drug‐induced liver injury in hospitalized patients: A matched case‐control study

Cited by 15 publications

References 30 publications

FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway

FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway

Astragalus Polysaccharide Enhances Voriconazole Metabolism under Inflammatory Conditions through the Gut Microbiota

A review of herb-induced liver injury in mainland china

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