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Introduction: Antipsychotic psychopharmacotherapy is associated with the risk of drug-induced liver injury (DILI). However, understanding specific risk factors remains challenging due to limited data. This study investigates the relationship between receptor binding affinities and occupancies of antipsychotics and their associated hepatotoxic risks. Methods: A disproportionality analysis with calculation of the Reporting Odds Ratio (ROR) and the Information Component (IC) was conducted using data from the FDA Adverse Event Reporting System (FAERS) to identify signals related to the Standardised MedDRA Query "drug-related hepatic disorders", which served as a proxy for drug-induced hepatotoxicity. This was followed by a pharmacoepidemiologic-pharmacodynamic approach to investigate the relationship between the ROR and substance-related receptor binding affinities and occupancy, which was estimated based on in vitro receptor-binding profiles. Results: Significant signals were identified for several antipsychotics, including chlorpromazine, loxapine, olanzapine, and quetiapine, with chlorpromazine and loxapine showing the highest RORs for DILI. Gender-specific analysis revealed a higher frequency of signals in female patients. Statistically significant negative correlations were identified between the ROR for drug-related hepatic disorders and the affinity for serotonin receptor 5-HT1A (r (17) = -0.68, p = 0.0012), while a positive correlation was observed for cholinergic receptors (r (17) = 0.46, p = 0.048). No significant correlations were found related to other receptors or drug properties. Conclusion: Our findings suggest that the serotonin and probably the cholinergic system may play a role in the development of DILI related to antipsychotic medications. The identification of antipsychotics with a higher association with DILI, such as chlorpromazine, underscores the need for careful monitoring in clinical practice. However, our findings need further longitudinal studies to confirm causality. A better understanding of the associations may inform clinical decision-making, particularly in patients with an increased susceptibility to liver damage. [ABSTRACT FROM AUTHOR]

Liver regeneration plays a crucial role in the recovery after liver injury induced by N-acetyl-p-aminophenol (APAP) . After APAP overdose, the degree of regeneration increases with the extent of liver injury, leading to the resolution of liver injury and spontaneous recovery in most cases. However, severe APAP overdose can impair liver regeneration and result in uncontrolled liver injury, even failure to recover or death in severe cases. Following APAP-induced liver injury, interactions between cells in the liver are essential for regenerative response. Liver regeneration is jointly regulated by multiple proliferative signaling pathways, involving various kinases, nuclear receptors, transcription factors, and coactivators. Severe APAP overdose can inhibit the activation of proliferative signaling pathways, thereby causing cell cycle arrest and impairing liver regeneration. Although liver regeneration plays a critical role in the repair of APAP-induced liver injury, the underlying mechanisms remain unclear. This article reviews the research advances in the role of liver regeneration in APAP-induced liver injury, in order to provide a reference for further basic research in this area. [ABSTRACT FROM AUTHOR]

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Here I detail the use of measures of permeability rate and solubility in predicting drug disposition characteristics through the utilization of the Biopharmaceutics Drug Disposition Classification System (BDDCS) and the Extended Clearance Classification System (ECCS) as well as the accuracy of the systems in predicting the major route of elimination and the extent of oral absorption of a new small molecule therapeutics. I compare the BDDCS and ECCS with the FDA Biopharmaceutics Classification System (BCS). I also detail the use of the BCS in predicting food effects and the BDDCS in predicting brain disposition of small molecule therapeutics and in validating DILI predictive metrics. This review provides an update of the current status of these classification systems and their uses in the drug development process.

Objective: Challenging differential diagnosis Background: Common causes of severely elevated transaminases, especially alanine transaminase, due to liver diseases include drug-induced liver injury and acute viral hepatitis, especially hepatitis E, which can present similarly in clinical practice. Broad differential diagnostic workup in patients with elevated transaminases is required to not overlook the possibility of hepatitis E infection. Case Report: We report on a 65-year-old asymptomatic man who was referred to the Emergency Department from the rehabilitation center due to markedly elevated liver transaminases. Physical examination revealed no jaundice or abdominal pain. Laboratory findings included severely elevated aspartate transaminase, alanine transaminase, and bilirubin levels. He was previously treated with imipenem/cilastatin and clindamycin for a surgical site infection of his jaw after the removal of a squamous cell carcinoma 2 weeks earlier. An ultrasound of the liver was unremarkable. Drug-induced liver injury was suspected, and all potentially hepatotoxic drugs, including antibiotics, were stopped. Due to the rapid and marked increase in liver transaminases, further tests were performed, including testing for hepatitis E. Serum anti-hepatitis E virus immunoglobulin M, immunoglobulin G antibodies, and hepatitis E virus-ribonucleic acid-polymerase chain reaction turned positive, and the diagnosis of hepatitis E was confirmed. Supportive care was applied. Liver transaminases decreased spontaneously. Conclusions: The diagnostic workup in patients with markedly elevated liver transaminases and suspected drug-induced liver injury should include the screening for hepatitis E. Making the correct diagnosis is crucial given the differing treatment approaches, the implications on further therapy, and the risk of contagion of hepatitis E. [ABSTRACT FROM AUTHOR]

Nutmeg, Myristica fragrans is used as a spice or medicinal plant to manage ailments. This study evaluated the nutritional and safety assessment of an aqueous extract of Myristica fragrans in Wistar rats. Thirty male Wistar rats weighing 180 - 240 g were randomly distributed into five groups: Control received distilled water, while 100, 200, 300, and 400 mg/kg body weight represented the treatment groups, respectively. The extract was orally administered to the animals for 28 days and then euthanized under anesthesia. Blood, serum, and liver homogenates from rats were used for biochemical analysis. The phytate and tannin contents were 0.38 mg/100 g and 0.15 mg/100 g, respectively. The calculated phytic acid to zinc ratio was 0.12. The respective percentage proximate components of the extract include moisture, ash, fat, protein, and carbohydrates: 10.61%, 45.42%, 5.95%, 1.81%, 13.78%, and 22.43%, respectively. Sodium, potassium, calcium, iron, magnesium, zinc, manganese, and lead were present in the extract. There was a significant increase (p<0.05) in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and acid phosphatase (ALP) activity in the groups treated with the extract compared to the control groups. Similarly, there was a significant increase (p<0.05) in serum total bilirubin and albumin concentrations in the extract treatment groups compared to control groups. On the contrary, there was a significant decrease (p<0.05) in the liver AST and ALP activity in the treatment groups compared to the control. The liver total protein and albumin concentrations showed a significant decrease (p<0.05) in the extract treatment groups compared to the control. There was a significant decrease (p<0.05) in the pack cell volume (PCV), haemoglobin (Hb), red blood cell (RBC), Mean cell volume (MCV), and platelet (PLT) levels in the animals in the extract treatment groups compared to the control group. Myristica fragrans is abundant in essential nutrients crucial for maintaining optimal physiological functions within the body, however, it is important to avoid excessive dosage or prolonged consumption which might be toxic to liver cells. [ABSTRACT FROM AUTHOR]

Due to the diverse application forms of Chinese herbal medicine products, the wide range of users, and the complex conditions of medication in China, adverse events including herb-induced liver injury(HILI)occur frequently in recent years. In order to further understand HILI and standardize its risk management and prevention and treatment measures, this article discusses the risk management, clinical evaluation, prevention, and treatment of HILI based on related clinical research advances and experience in recent years. In the multiple links of traditional Chinese medicine including production and clinical application after marketing, the establishment of a comprehensive control system is of great importance for the prevention and treatment of HILI and other adverse events, involving product quality control, patient safety education, rational drug use by clinicians, regular monitoring, and graded and classified treatment, which provides a reference for the rational and safe clinical use of Chinese herbal medicine in the future. [ABSTRACT FROM AUTHOR]

In order to deal with the problem of the safety of Chinese herbal medicine in a scientific way and further meet the growing health needs of people, it is particularly important to deepen the research on herb-induced liver injury. This article elaborates on the phenotypic characteristics and toxicological mechanisms of herb-induced liver injury and emphasizes that it should not only rely on the previous knowledge of the toxicity of Chinese herbal medicine, but also understand the new types of idiosyncratic toxicity, indirect toxicity, and mixed toxicity, which provide a new perspective for understanding the toxicological mechanisms of herb-induced liver injury and are of great importance to investigate the phenotype and toxicological mechanism of herb-induced liver injury. [ABSTRACT FROM AUTHOR]

With the increasingly wide application of herbal medicines and dietary supplements worldwide, herb-induced liver injury (HILI) has become an important etiology of drug-induced liver injury. Due to the diverse manifestations of HILI, the difficulty in medical history collection, and the lack of specific biomarkers, how to identify suspected patients and make a correct diagnosis has become a major challenge in practice. Causality assessment is commonly used in the diagnosis of HILI, but there is still a lack of prospective cohort studies with a large sample size. In addition, further studies are needed to search for the specific biomarkers for the diagnosis of HILI. The diagnosis and differential diagnosis of HILI are challenging, and currently there is still no universally accepted uniform and standard method for the diagnosis of all-cause HILI. [ABSTRACT FROM AUTHOR]

Herb-induced liver injury (HILI) shows a high incidence rate and has great impacts on the clinical medication safety of traditional Chinese medicine and the healthy development of the industry. In recent years, the research on HILI has attracted wide attention and made remarkable progress, and related clinical diagnosis and treatment guidelines have been formulated and updated by the academic organizations in China and globally. This article compares the recent guidelines on HILI formulated by different organizations and elaborates on the main achievements in terms of mechanism of toxicity, clinical diagnosis and disease assessment, risk factors, and clinical prevention and treatment, and it also proposes the unmet needs, the research difficulties that need to be taken seriously, and possible prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

With the wide application of traditional Chinese medicine (TCM)globally and combined drug use in clinical practice, there have been significant increases in herb-induced liver injury (HILI) events and drug safety events, bringing great challenges to the research and development of new TCM drugs and the development of the TCM industry. At present, there are still shortcomings in systematically summarizing the effect of combined drug use on HILI and analyzing its clinical features, pathogenesis and interaction mechanism, especially the research on pharmacodynamics and pharmacotoxicology processes after the combination of TCM and Western drugs. It is urgently needed to further construct an integrated research system, especially in the aspects of target molecules, intercellular communication, tissue crosstalk, and in vivo toxicity assessment. Based on the basic research combining clinical and fundamental studies, it is necessary to put forward HILI prevention and control strategies in accordance with TCM theory and application rules, which will provide fundamental support and reliable evidence for improving the level of combined use of TCM and Western drugs in the context of diseases and syndromes. [ABSTRACT FROM AUTHOR]

Herb-induced liver injury (HILI) tends to have complex toxic material basis and toxic mechanism, which greatly affects the safety of traditional Chinese medicine. This article summarizes the main toxic components of Chinese herbal medicine causing liver injury and their mechanism of action. The toxic components of Chinese herbal medicine causing liver injury can be classified into two categories of drug-derived and non-drug-derived toxic components. Drug-derived toxic components mainly include alkaloids, terpenoids, anthraquinones, and phenylpropanoids, and their mechanism of action involves oxidative stress, apoptosis and necrosis, CYP450 enzymes, and genotoxicity. Non-drug-derived toxic components mainly include pesticide residues, sulfur dioxide residues, heavy metals, fungi, and plant growth regulators, and their mechanisms involve oxidative stress, apoptosis, metabolic disorders, and CYP450 enzymes. On this basis, this article further proposes the unsolved problems and research difficulties, in order to promote the basic research on the hepatotoxicity of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have revealed a substantial between-centre variability in DCE-MRI biomarkers of hepatocellular function in rats. This study aims to identify the main sources of variability by comparing data measured at different centres and field strengths, at different days in the same subjects, and over the course of several months in the same centre. Materials and methods: 13 substudies were conducted across three facilities on two 4.7 T and two 7 T scanners using a 3D spoiled gradient echo acquisition. All substudies included 3–6 male Wistar-Han rats each, either scanned once with vehicle (n = 76) or twice with either vehicle (n = 19) or 10 mg/kg of rifampicin (n = 13) at follow-up. Absolute values, between-centre reproducibility, within-subject repeatability, detection limits, and effect sizes were derived for hepatocellular uptake rate (Ktrans) and biliary excretion rate (kbh). Sources of variability were identified using analysis of variance and stratification by centre, field strength, and time period. Results: Data showed significant differences between substudies of 31% for Ktrans (p = 0.013) and 43% for kbh (p < 0.001). Within-subject differences were substantially smaller for kbh (8%) but less so for Ktrans (25%). Rifampicin-induced inhibition was safely above the detection limits, with an effect size of 75 ± 3% in Ktrans and 67 ± 8% in kbh. Most of the variability in individual data was accounted for by between-subject (Ktrans = 23.5%; kbh = 42.5%) and between-centre (Ktrans = 44.9%; kbh = 50.9%) variability, substantially more than the between-day variation (Ktrans = 0.1%; kbh = 5.6%). Significant differences in kbh were found between field strengths at the same centre, between centres at the same field strength, and between repeat experiments over 2 months apart in the same centre. Discussion: Between-centre bias caused by factors such as hardware differences, subject preparations, and operator dependence is the main source of variability in DCE-MRI of liver function in rats, closely followed by biological between-subject differences. Future method development should focus on reducing these sources of error to minimise the sample sizes needed to detect more subtle levels of inhibition. [ABSTRACT FROM AUTHOR]

Artemisinin, an ancient Chinese herbal remedy known colloquially as "Qinghao", is now used as treatment for malaria as recommended by the World Health Organisation. There have been few reports of artemisinin-induced liver injury. Most of these instances of hepatotoxicity are reportedly due to prolonged use of herbal remedies containing artemisinin. To our knowledge, we report the first case of intrahepatic ductopenia in a patient with cholestatic liver injury after artemisinin use. [ABSTRACT FROM AUTHOR]

Background: Several factors contribute to post-anesthetic hepatic dysfunction, including a decrease in oxygen supply to the liver, direct physical compression of the liver, viral hepatitis, blood transfusions, preexisting hepatic dysfunction, and the use of hepatotoxic drugs. Diagnosing volatile anesthetic drug-induced liver injury (VA-DILI) involves excluding these causes. Case: The patient underwent total mastectomy under anesthesia using sevoflurane. He had diabetes, and no abnormal results were found on preoperative laboratory examinations, and surgery was uneventful. Abnormal laboratory findings were observed after surgery, including an aspartate aminotransferase level of 1,417 IU/L, an alanine aminotransferase level of 2,176 IU/L, and a total bilirubin level of 3.8 mg/dl. He presented with symptoms of mild icteric sclera, fatigue, and pruritus. After ruling out other causes of liver injury, we concluded that these results indicated VA-DILI. Conclusions: VA-DILI, though rare, we should be aware of the association between the disease and the use of halogenated anesthetics. [ABSTRACT FROM AUTHOR]

Caveolin-1 (CAV1) is a structural protein of caveolae on the plasma membrane and is an important regulatory factor for liver function. CAV1 regulates hepatic lipid deposition, lipid and glucose metabolism, mitochondrial function, and hepatocyte proliferation through various molecular pathways. Therefore, CAV1 plays a crucial role in maintaining liver physiology during the metabolic regulatory processes such as hepatic steatosis and hepatocyte proliferation. Furthermore, CAV1 is also involved in the development and progression of different types of liver injury, hepatitis, and liver cirrhosis. This article reviews the role of CAV1 in liver-related diseases and its mechanism in the regulation of liver macrophages, so as to provide a theoretical basis for targeting CAV1 in the treatment of liver-related diseases. [ABSTRACT FROM AUTHOR]

Drug-induced autoimmune-like hepatitis (DI-ALH) is a special clinical phenotype of drug-induced liver injury and has similar clinical features and laboratory test results to autoimmune hepatitis, and it is often difficult to distinguish them through liver biopsy. Therefore, correct differential diagnosis DI-ALH and autoimmune hepatitis is a crucial and difficult point in clinical practice. This article analyzes the research advances in the pathogenesis, clinical features, diagnosis and treatment, and prognosis of DI-ALH, in order to provide ideas for the diagnosis and treatment of such diseases among clinicians. [ABSTRACT FROM AUTHOR]

Objective To determine the scores of patients with a confirmed diagnosis of drug-induced liver injury (DILI) using Roussel Uclaf Causality Assessment Method (RUCAM), Maria ＆ Victorino assessment scale, and Revised Electronic Causality Assessment Method (RECAM), to compare the accuracy of the three scales in diagnosis, and to investigate their clinical significance in the diagnosis of DILI. Methods A total of 98 patients with a confirmed diagnosis of DILI who were hospitalized in Peking University First Hospital from January 2011 to December 2022 were enrolled, with liver biopsy results supporting DILI and a clear history of medication. Clinical data were collected from all subjects, and the above causality assessment scales were used for scoring. The chi-square test was used to analyze the diagnostic accuracy of the causality assessment scales, and the weighted kappa coefficient was used to analyze the consistency between the three scales. Results For all patients with DILI enrolled, RECAM had the highest accuracy, with a significant difference compared with RUCAM (χ² =5.667, P=0.017). RUCAM and RECAM had moderate consistency in diagnosis (κw=0.469), while RECAM and Maria ＆ Victorino scale had poor consistency (κw=0.156). For the patients with acute DILI, RECAM, RUCAM, and Maria ＆ Victorino scales had a diagnostic inconsistency rate of 3.7%, 11.1%, and 42.6%, respectively; for the patients with hepatocellular type DILI, the three scales of a diagnostic inconsistency rate of 8.9%, 21.4%, and 62.5%, respectively; for the patients with cholestasis type or mixed type DILI, the three scales of a diagnostic inconsistency rate of 10.0%, 22.5%, and 47.5%, respectively. Conclusion The use of RECAM and RUCAM scales in acute DILI can improve diagnostic rate, and for hepatocellular type DILI and DILI with the clinical manifestation of cholestasis (cholestasis type DILI and mixed type DILI), the use of RECAM and RUCAM scales can also improve diagnostic rate. The selection of causality assessment scales with a relatively high accuracy based on the course and clinical classification of the disease may help to further improve clinical diagnostic rate. [ABSTRACT FROM AUTHOR]

IntroductionAntipsychotic psychopharmacotherapy is associated with the risk of drug-induced liver injury (DILI). However, understanding specific risk factors remains challenging due to limited data. This study investigates the relationship between receptor binding affinities and occupancies of antipsychotics and their associated hepatotoxic risks.MethodsA disproportionality analysis with calculation of the Reporting Odds Ratio (ROR) and the Information Component (IC) was conducted using data from the FDA Adverse Event Reporting System (FAERS) to identify signals related to the Standardised MedDRA Query “drug-related hepatic disorders”, which served as a proxy for drug-induced hepatotoxicity. This was followed by a pharmacoepidemiologic-pharmacodynamic approach to investigate the relationship between the ROR and substance-related receptor binding affinities and occupancy, which was estimated based on in vitro receptor-binding profiles.ResultsSignificant signals were identified for several antipsychotics, including chlorpromazine, loxapine, olanzapine, and quetiapine, with chlorpromazine and loxapine showing the highest RORs for DILI. Gender-specific analysis revealed a higher frequency of signals in female patients. Statistically significant negative correlations were identified between the ROR for drug-related hepatic disorders and the affinity for serotonin receptor 5-HT1A (r (17) = -0.68, p = 0.0012), while a positive correlation was observed for cholinergic receptors (r (17) = 0.46, p = 0.048). No significant correlations were found related to other receptors or drug properties.ConclusionOur findings suggest that the serotonin and probably the cholinergic system may play a role in the development of DILI related to antipsychotic medications. The identification of antipsychotics with a higher association with DILI, such as chlorpromazine, underscores the need for careful monitoring in clinical practice. However, our findings need further longitudinal studies to confirm causality. A better understanding of the associations may inform clinical decision-making, particularly in patients with an increased susceptibility to liver damage.

Homeopathic remedies made primarily from eggshells, and therefore calcium, can be marketed for treatment of back pain and vaginal discharge. We present a case of a 23-year-old otherwise healthy woman who presented with acute liver failure (ALF) ultimately requiring liver transplantation as a result of taking increased doses of a homeopathic product with the primary ingredient of eggshells. Although relatively uncommon compared with medications such as acetaminophen, herbal supplements have been reported to cause drug-induced liver injury (DILI), thought to be primarily due to contaminants. This is the first known report of DILI resulting from a homeopathic product with the primary ingredient of eggshells, and it demonstrates the importance of early ALF recognition and treatment, as well as the importance of practicing caution when using homeopathic supplements.

Objective: Unusual clinical course Background: Close observation, statins, fibrate treatment, and lifestyle changes can safely manage asymptomatic individuals with severe hypertriglyceridemia (HTG) and minimal risk of symptom development. However, the risk of medication-induced liver injury in patients taking statin-fibrate makes management more challenging, and may require hospital admission and close monitoring with follow-up. Case Report: We present a rare case of a 43-year-old man with asymptomatic severe HTG exceeding 11.370 mg/dL with mixed hyperlipidemia, managed initially with high-intensity statins and fibrate. However, due to the concurrent use of statin and fibrates, the patient subsequently developed an acute liver injury. Hence, the oral medications had to be stopped, and the patient was admitted to the hospital for an insulin drip. Even during the hospital course, the patient's triglyceride (TG) levels showed resistance to the recommended dose of insulin and he required a higher insulin dose. He was discharged on fenofibrate and subcutaneous insulin to keep the TG level under 500. Fibrate was stopped, and high-intensity statin was used as primary prevention with lifestyle modifications. Conclusions: This instance highlights the necessity of increased cognizance and cooperative endeavors in handling severe asymptomatic HTG. Our results highlight the significance of further research into the management of severe asymptomatic HTG in cases of injury to the liver. This work adds essential knowledge to the ongoing discussion about managing a rare case complicated by acute liver injury. [ABSTRACT FROM AUTHOR]

Polygonum multiflora (PM), a commonly used Chinese herbal medicine in clinical practice, has been associated with frequent reports of liver injury in recent years, and the medication safety of PM has attracted more and more attention in China and globally. This article reviews the recent research advances in the signaling pathways and mechanisms of PM in causing drug induced liver injury (DILI) and aims to provide new ideas for the proper and rational use of PM in clinical practice. The results show that PM is involved in the regulation of various signaling pathways, and it leads to the death of hepatocytes by destroying mitochondrial function, exacerbating bile acid accumulation, and inducing immune response, oxidative stress, and endoplasmic reticulum stress, thereby inducing the development and progression of DILI through multiple targets, pathways, and levels. [ABSTRACT FROM AUTHOR]

Objective To investigate the influencing factors for the clinical outcome of patients with drug-induced liver injury (DILI), and to establish a nomogram prediction model for validation. Methods A retrospective analysis was performed for the general information and laboratory data of 188 patients with DILI who were admitted to Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology from January 2017 to December 2022, and according to their clinical outcome, they were divided into good outcome group with 146 patients and poor outcome group with 42 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the independent influencing factors for the clinical outcome of DILI patients. R Studio 4.1.2 software was used to establish a nomogram model, and calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to perform internal validation. Results The univariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI, platelet count, cholinesterase, albumin, prothrombin time activity, IgM, and IgG were associated with adverse outcomes in patients with DILI. The multivariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI (odds ratio ［OR］=0.072，95% confidence interval ［CI］：0.022—0.213，P<0.001), clinical classification (OR=0.463，95%CI：0.213—0.926，P=0.039), alanine aminotransferase (OR=0.999，95%CI：0.998—1.000，P=0.025), prothrombin time activity (OR=0.973，95%CI：0.952—0.993, P=0.011), and IgM (OR=1.456，95%CI：1.082—2.021，P=0.015) were independent influencing factors for clinical outcome in patients with DILI. The nomogram prediction model was established, and after validation, the calibration curve was close to the reference curve. The area under the ROC curve was 0.829, and the DCA curve showed that the model had good net clinical benefit. Conclusion The nomogram prediction model established in this study has good clinical calibration, discriminative ability, and application value in evaluating the clinical outcome of patients with DILI. [ABSTRACT FROM AUTHOR]

Background & Aims: Currently, there is limited knowledge on the clinical profile of drug-induced liver injury (DILI) in Chinese children. We aimed to assess the clinical characteristics, suspected drugs, and outcomes associated with pediatric DILI in China. Methods: This nationwide, multicenter, retrospective study, conducted between 2012 and 2014, analyzed 25,927 cases of suspected DILI at 308 medical centers using the inpatient medical register system. Utilizing the Roussel Uclaf causality assessment method score, only patients with scores ≥6 or diagnosed with DILI by three experts after scoring

Objective To investigate the change in intestinal flora and its association with liver CYP2E1 in mice with li-ver injury caused by high-intensity atorvastatin (ATO). Methods According to the treatment method, 40 C57BL/6 mice were divided into low-intensity ATO group (ATO-L group), medium-intensity ATO group (ATO-M group), high-intensity ATO group (ATO-H group), and control group (CON group), with 10 rats in each group. The mice in the ATO-L group, the ATO-M group, and the ATO-H group were given 1 mL normal saline containing ATO at doses of 10, 20, and 30 mg/kg, respectively, by gavage, and those in the CON group were given an equal volume of normal saline by gavage, for 4 consecutive weeks. HE staining and transmission electron microscopy were used to observe liver pathological state. Related methods were used to measure the se-rum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10, the activity of superoxide dismutase (SOD) in liver tissue, and the mRNA expression level of CYP2E1 in liver tissue. 16SrDNA sequencing was used to analyze the distribution of intestinal flora in fresh feces of mice, and a correlation analysis was conducted to investigate the correlation of the relative abundance of bacterial genera with significant diffe-rences with the mRNA expression level of CYP2E1 and SOD activity in liver tissue. Results HE staining and transmission electron microscopy showed varying degrees of liver injury in the ATO-M and ATO-H groups. There were significant differences in the serum levels of ALT, AST, IL-6, and TNF-α and SOD activity in liver tissue between groups (F=4.57-7.74,P