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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]

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]

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]

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.

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]

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]

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

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.

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]

Drug-induced liver injury is caused by the drug itself and/or its metabolites during drug use or occurs due to hypersensitivity or reduced tolerance to the drug in a particular body type. In the last three years of the diagnosis and treatment of coronavirus disease 2019 (COVID-19), antiviral drugs have played a very important role, but there are many reports on liver injury caused by anti-COVID-19 drugs in China and globally, with unknown pathogenesis of liver injury caused by such drugs. This article reviews the research advances in the types of antiviral drugs for COVID-19 and their mechanism in inducing liver injury, in order to promote the rational use of antiviral drugs. [ABSTRACT FROM AUTHOR]

Aims: To determine associations between anabolic‐androgenic steroid (AAS) use‐related morbidity including cardiovascular disease (CVD) and engagement to health services. Methods: In this cross‐sectional study, 90 males with at least 12 months cumulative current or former use of AAS were included. The participants were divided into a treatment‐seeking group (TSG) and a non‐treatment seeking group (non‐TSG) based on their responses to a self‐report web questionnaire. All participants were screened for symptoms that could be indicative of CVD through a clinical interview, and examined with blood samples, blood pressure measurements and transthoracic echocardiography. Results: In the total sample (n = 90), mean age was 39 ± 11 years with cumulative AAS use of 12 ± 9 years. Among men in the TSG with current use there were higher prevalence of dyspnoea (50% vs 7%) and reduced left ventricular ejection fraction (LVEF) in conjunction with left ventricular hypertrophy (LVH) (36 vs. 9%) and/or high blood pressure (55% vs. 19%) compared to men in the non‐TSG. Among men with current AAS use and established LVEF <50% (n = 25) or LVH (n = 21), 44% (11) and 43% (9) respectively, had never engaged health services due to AAS‐related adverse effects. Deviant liver‐ and kidney parameters were frequently observed in the total sample but without between‐group differences. Conclusions: Treatment‐seeking behavior among current AAS users may be associated with increased levels of dyspnoea and established CVD. Despite objective signs of severe CVD among a substantial amount of study participants, it is of great concern that the majority had never sought treatment for AAS‐related concerns. [ABSTRACT FROM AUTHOR]

Background and Purpose: Liver injury after Covid‐19 vaccine has been described, although the incidence was not well established. We aimed to compare cumulative incidence of new onset liver test alteration after Covid‐19 vaccination, and to compare with an historical control of influenza vaccination. Methods: We conducted a retrospective cohort study which included adults who received at least one dose of Covid‐19 vaccine from January 1 to May 30, 2021 and a control group who received a single dose of influenza vaccine during 2019, in a tertiary medical center from Argentina. Results: We included 29 798 patients in Covid‐19 vaccine group and 24 605 in influenza vaccine group. Liver function tests were performed in 7833 (26.9%) in Covid‐19 vaccine group and 8459 (34.37%) in influenza vaccine group. Cumulative incidence at 90 days of new onset liver enzyme test alteration was 4.7 per 1000 (95% 4.0–5.5) for Covid‐19 group, and 5.1 per 1000 (95% 4.3–6.1) for the influenza vaccine group (p value = 0.489). Two patients in the Covid‐19 vaccine group developed immune mediated liver injury. Conclusions: We found no difference in liver test alteration between groups. These findings support the safety of Covid‐19 vaccines. While we have identified two cases that are consistent with immune mediated liver injury following COVID‐19 vaccination, we believe that the available data is insufficient to attribute them solely to the vaccination. [ABSTRACT FROM AUTHOR]

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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

Objective To investigate the influence of high-dose atorvastatin on bile acid metabolism in mice with liver injury and its mechanism. Methods A total of 40 specific pathogen-free male C57BL/6 mice were randomly divided into normal saline group (group A) and low-, middle-, and high-dose atorvastatin groups (groups B, C, and D, respectively), with 10 mice in each group. After 30 days of intragastric administration of normal saline and atorvastatin at a dose of 10, 20, and 30 mg/kg, respectively, orbital blood was collected from the mice in each group, and these groups were compared in terms of the serum levels of total bile acid (TBA), endotoxin (ET), aspartate aminotransferase (AST), and alanine aminotransferase (ALT); after liver tissue samples were collected, HE staining was performed to observe the pathological changes of liver tissue, and PCR was used to measure the mRNA expression levels of the bile acid metabolism-related genes farnesoid X receptor (FXR) and multidrug resis-tance-associated protein 2 (MRP2) in liver tissue. Results The mice in group D had slight swelling, sporadic inflammatory cell infiltration, and feather-like degeneration in liver tissue. Compared with the other groups, group D had significant increases in the serum levels of TBA, ET, AST, and ALT (P

Background and aims: Some drug-induced liver injury (DILI) cases may become chronic, even after drug withdrawal. Radiomics can predict liver disease progression. We established and validated a predictive model incorporating the clinical characteristics and radiomics features for predicting chronic DILI. Methods: One hundred sixty-eight DILI patients who underwent liver gadolinium-diethylenetriamine pentaacetate-enhanced magnetic resonance imaging were recruited. The patients were clinically diagnosed using the Roussel Uclaf causality assessment method. Patients who progressed to chronicity or recovery were randomly divided into the training (70%) and validation (30%) cohorts, respectively. Hepatic T1-weighted images were segmented to extract 1672 radiomics features. Least absolute shrinkage and selection operator regression was used for feature selection, and Rad-score was constructed using support vector machines. Multivariable logistic regression analysis was performed to build a clinic-radiomics model incorporating clinical characteristics and Rad-scores. The clinic-radiomics model was evaluated for its discrimination, calibration, and clinical usefulness in the independent validation set. Results: Of 1672 radiomics features, 28 were selected to develop the Rad-score. Cholestatic/mixed patterns and Rad-score were independent risk factors of chronic DILI. The clinic-radiomics model, including the Rad-score and injury patterns, distinguished chronic from recovered DILI patients in the training (area under the receiver operating characteristic curve [AUROC]: 0.89, 95% confidence interval [95% CI]: 0.87–0.92) and validation (AUROC: 0.88, 95% CI: 0.83–0.91) cohorts with good calibration and great clinical utility. Conclusion: The clinic-radiomics model yielded sufficient accuracy for predicting chronic DILI, providing a practical and non-invasive tool for managing DILI patients. [ABSTRACT FROM AUTHOR]

The predominant catechin in green tea, epigallocatechin gallate (EGCG), may be hepatotoxic in high doses. Our objective was to investigate the influence of catechol-O-methyltransferase (COMT) and uridine 5'-diphospho-glucuronosyltransferase 1A4 (UGT1A4) genotypes on changes in liver injury biomarkers in response to long-term, high-dose green tea extract (GTE) supplementation among postmenopausal women. A secondary analysis was conducted using data from the Minnesota Green Tea Trial (N = 1,075), in which participants were randomized to consume high-dose GTE (843 mg/day EGCG) or placebo capsules for 12 months. Analysis of covariance adjusting for potential confounders was performed to examine changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST: ALT ratio, and alkaline phosphatase from baseline to months 3, 6, 9, and 12 across COMT and UGT1A4 genotypes. Mean age and BMI within the GTE group (n = 400) were 59.8 yrs and 25.1 kg/m2, respectively, and 98% of subjects were white. From baseline to month 3, mean AST: ALT ratio change was +1.0% in the COMT (rs4680) A/G genotype versus −4.8% in the A/A genotype (p = 0.03). From baseline to months 6 and 9, respectively, mean ALT change was +78.1% and +82.1% in the UGT1A4 (rs6755571) A/C genotype versus +28.0% and +30.1% in the C/C genotype (p < 0.001 and p = 0.004, respectively). The UGT1A4 (rs6755571) A/C genotype may be an important risk factor for clinically-relevant serum transaminase elevations with 6-9 months of high-dose GTE supplementation among postmenopausal women. Understanding the genetic underpinnings of GTE-related hepatotoxicity may allow for a genetically-informed paradigm for therapeutic use of GTE. [ABSTRACT FROM AUTHOR]

Objective: Unknown etiology. Background: Pulmonary embolism secondary to deep vein thrombosis (DVT) with cor pulmonale is commonly associated with risk factors including surgery, cancer, and prolonged immobility. Cocaine is known to cause vasoconstriction and has a prothrombotic effect. Prolonged and heavy use of cocaine can also cause inflammation and liver damage. However, data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. Case Report: A 34-year-old man with no significant medical history except for episodic cocaine use presented in respiratory distress. Workup revealed submassive pulmonary embolism with pulmonary infarctions complicated by pneumonia, hypoxemic respiratory failure, and anemia. He was treated with anticoagulation and intensive care. On day 5 of hospitalization, the patient had an acute hepatic injury. His alanine aminotransferase level peaked at over 2000 IU/L on day 7, until finally tapering. Liver failure was found to be secondary to cocaine use. Liver enzyme levels improved with supportive care. He was discharged with apixaban and continued liver enzyme monitoring. Conclusions: When investigating the cause of venous thromboembolism and transaminitis, evaluating cocaine use via patient history or laboratory analysis of cocaine and its metabolites should be considered. Cocaine is known to cause vasoconstriction and has a prothrombotic effect, although data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. Further investigation, such as cohort studies, could help strengthen our understanding of the relationship between cocaine use, acute hepatic injury, and pulmonary embolism. [ABSTRACT FROM AUTHOR]

The Biopharmaceutics Drug Disposition Classification system (BDDCS) is a four-class approach based on water solubility and extent of metabolism/permeability rate. Based on the BDDCS class to which a drug is assigned, it is possible to predict the role of metabolic enzymes and transporters on the drug disposition of a new molecular entity (NME) prior to its administration to animals or humans. Here, we report a total of 1475 drugs and active metabolites to which the BDDCS is applied. Of these, 379 are new entries, and 1096 are revisions of former classification studies with the addition of references for the approved maximum dose strength, extent of the systemically available drug excreted unchanged in the urine, and lowest solubility over the pH range 1.0-6.8 when such information is available in the literature. We detail revised class assignments of previously misclassified drugs and the literature analyses to classify new drugs. We review the process of solubility assessment for NMEs prior to drug dosing in humans and approved dose classification, as well as the comparison of Biopharmaceutics Classification System (BCS) versus BDDCS assignment. We detail the uses of BDDCS in predicting, prior to dosing animals or humans, disposition characteristics, potential brain penetration, food effect, and drug-induced liver injury (DILI) potential. This work provides an update on the current status of the BDDCS and its uses in the drug development process.