Pathogenesis of liver injury caused by antiviral drugs for coronavirus disease 2019 / 临床肝胆病杂志

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.

Development of an in vitro screening method for idiosyncratic hepatotoxic components in traditional Chinese medicine: a case study with Epimedii Folium and Psoraleae Fructus / 药学学报

Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.

Role of mesenchymal stem cells and their exosomes in the treatment of drug-induced liver injury / 临床肝胆病杂志

The incidence rate of drug-induced liver injury （DILI） is increasing year by year with unknown mechanisms， and the treatment methods for DILI mainly include drugs， liver support systems， and liver transplantation， all of which have certain limitations. Therefore， the search for safer and more effective treatment methods has become a research hotspot at present. Studies have shown that mesenchymal stem cells and their exosomes can alleviate liver injury by reducing liver inflammation， promoting hepatocyte proliferation and regeneration， inhibiting the apoptosis of hepatocytes， improving oxidative stress， and regulating immunity. This article briefly reviews the role of mesenchymal stem cells and their exosomes in the treatment of DILI， so as to provide a reference for further research.

Mechanism of action of Polygonum multiflorum in inducing liver injury： A study based on signaling pathways / 临床肝胆病杂志

Polygonum multiflorum （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.

Diagnosis and treatment principles of liver injury induced by antithyroid drugs / 临床肝胆病杂志

Pharmacotherapy is the primary treatment method for hyperthyroidism. Antithyroid drugs can induce liver injury， and the diagnosis of drug-induced liver injury is mostly exclusive based on medical history collection， clinical symptoms， serum biochemistry， radiological examination， and histology. According to the severity of liver injury， drug-induced liver injury can be classified into mild， moderate， severe， and fatal degrees. Drug withdrawal may not be necessary for patients with mild liver injury， but regular monitoring of liver function is required； in severe cases， patients may develop liver failure， which may lead to a mortality rate， and early identification， timely drug withdrawal， and reasonable pharmacotherapy can help to avoid fatal consequences. The treatment principles of liver injury induced by antithyroid drugs include promoting the recovery of liver injury， preventing the severe exacerbation and chronicity of liver injury， and reducing the risk of death. Standardized medication， timely monitoring， early identification， and early treatment are important measures for the prevention and treatment of liver injury induced by antithyroid drugs.

Influencing factors for the prognosis of patients with drug-induced liver injury and establishment of a nomogram model / 临床肝胆病杂志

ObjectiveTo 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. MethodsA 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. ResultsThe 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. ConclusionThe 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.

Near-fatal cocaine intoxication in an infant with thrombotic microangiopathy associated with multiple organ failure / Intoxicação grave por cocaína em criança com microangiopatia trombótica associada à falência múltipla de órgãos

ABSTRACT Objective: To report a pediatric case of drug-induced thrombotic microangiopathy caused by cocaine Case description: We report a nine-month-old patient who developed thrombotic microangiopathies after extreme cocaine intoxication, multiple organ dysfunction syndrome with hemodynamic dysfunction, anuric renal failure, liver failure, encephalopathy, and myocardial injury, corresponding phenotypically to thrombocytopenia-associated multiple organ failure. The patient received continuous venous hemofiltration and therapeutic plasma exchange, recovering satisfactorily. She was discharged after 30 days of hospitalization under the guidance of the childcare service, and was healthy after one year of follow-up. Toxicological samples confirmed high levels of cocaine and derivatives in blood, urine and hair. Comments: To our knowledge, this is the first reported pediatric case. There are particularities of cocaine intoxication pathophysiology that can trigger thrombotic microangiopathies because of vasoconstriction, direct endothelial injury, platelet activation, and increasing von Willebrand factor and fibrinogen levels. All of which results in a prothrombotic state, inflammatory dysregulation, and microvascular thrombi. The increasing use of cocaine, especially among young adults, puts children at high risk of toxicity, either by passive unintentional exposure, or abuse due to the increased availability in homes.

RESUMO Objetivo: Relatar um caso pediátrico de microangiopatia trombótica induzida por drogas causada por cocaína Descrição do caso: Relatamos uma paciente de nove meses de idade que desenvolveu microangiopatia trombótica após intoxicação extrema por cocaína, síndrome de disfunção de múltiplos órgãos com disfunção hemodinâmica, insuficiência renal anúrica, insuficiência hepática, encefalopatia e lesão miocárdica, correspondendo fenotipicamente à falência múltipla de órgãos associada à trombocitopenia. A paciente recebeu hemofiltração venosa contínua e plasmaférese terapêutica, recuperando-se satisfatoriamente. Recebeu alta após 30 dias de internação sob orientação do serviço de puericultura e estava saudável após um ano de seguimento. Amostras toxicológicas confirmaram altos níveis de cocaína e derivados no sangue, urina e cabelos. Comentários: Até onde sabemos, este é o primeiro caso pediátrico relatado. Existem particularidades da fisiopatologia da intoxicação por cocaína que podem desencadear a microangiopatia trombótica devido à vasoconstrição, lesão endotelial direta, ativação plaquetária e aumento do fator de von Willebrand e dos níveis de fibrinogênio. Tudo isso resulta em um estado pró-trombótico, desregulação inflamatória e trombos microvasculares. O uso crescente de cocaína, principalmente entre adultos jovens, coloca as crianças em alto risco de toxicidade, seja por exposição passiva não intencional ou abuso devido à maior disponibilidade nas residências.

Osteonecrose dos maxilares relacionada ao uso demedicamentos: características patológicas, diagnóstico,prevenção e estratégias terapêuticas / Medication-related osteonecrosis of the jaws: pathological characteristics, diagnosis, prevention and therapeutic strategies

Objetivo: Este trabalho tem como propósito fornecer uma análise abrangente das características clínicas, etiológicas, radiográficas e histopatológicas da osteonecrose dos maxilares relacionada ao uso de medicamentos, além de abordar os métodos de diagnóstico, prevenção e estratégias terapêuticas. Materiais e métodos: foi realizada uma busca por artigos científicos publicados no período de 2015 a 2023, utilizando as bases de dados Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) e ScienceDirect. Conclusão: Embora infrequente, há um considerável potencial de ocorrência de osteonecrose dos maxilares em pacientes submetidos a terapia prolongada com medicamentos antirreabsortivos e antiangiogênicos, especialmente quando não são adotadas medidas preventivas adequadas. A implementação de práticas preventivas, a vigilância das condições bucais e a colaboração de uma equipe multidisciplinar são fundamentais para reduzir os riscos associados a essa condição patológica.(AU)

Objective: This work aims to provide a comprehensive analysis of the clinical, etiological, radiographic and histopathological characteristics of Medication-Related Jaw Osteonecrosis, in addition to addressing diagnostic methods, prevention and therapeutic strategies. Materials and methods: A search was carried out for scientific articles published between 2015 and 2023, using the Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) and ScienceDirect databases. Conclusion: Although infrequent, there is a considerable potential for osteonecrosis of the jaw to occur in patients undergoing prolonged therapy with antiresorptive and antiangiogenic medications, especially when adequate preventive measures are not adopted. The implementation of preventive practices, surveillance of oral conditions and the collaboration of a multidisciplinary team are essential to reduce the risks associated with this pathological condition.(AU)

Hepatotoxicidad inducida por clozapina: reporte de caso y revisión breve de la literatura

Introducción: Los antipsicóticos son medicamentos que pueden producir elevaciones transitorias de las enzimas hepáticas. La clozapina es un antipsicótico atípico usado en el tratamiento de la esquizofrenia refractaria a los antipsicóticos convencionales y existe evidencia que puede producir elevaciones de las transaminasas hepáticas, expresión de dafño hepático con patrón hepatocelular. Métodos: Reporte de caso y revisión no sistemática de la literatura relevante. Presentación del caso: Una mujer de 39 años con diagnóstico de esquizofrenia paranoide acudió a un servicio de urgencias de un hospital general por náuseas, vómitos e ictericia que apareció tras el inicio de clozapina. No hubo mejoría clínica de la paciente durante la hospitalización, que falleció a los 44 días de su ingreso. Revisión de la literatura: La clozapina puede elevar las cifras de función hepática de manera transitoria y asintomática. Hay criterios clínicos para recomendar la suspensión de este antipsicótico. Conclusiones: Este caso es el tercero en la literatura que registra un desenlace fatal tras un cuadro de hepatotoxicidad inducido por clozapina. © 2021 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.

Introduction: Antipsychotics are drugs that can produce transient elevations of hepatic enzymes. Clozapine is an atypical antipsychotic used in treatment-resistant schizophrenia and there is evidence that it can produce elevations of hepatic transaminases, expression of liver damage in a hepatocellular pattern. Methods: Case report and non-systematic review of the relevant literature. Case presentation: A 39-year-old woman with a diagnosis of paranoid schizophrenia attended the emergency department of a general hospital for nausea, vomiting and jaundice that appeared after the initiation of clozapine. There was no clinical improvement during hospitalization, and death occurred after 44 days. Literature review: Clozapine can increase the liver enzyme levels transiently and asymptomatically; however, there are clinical criteria that recommend the withdrawal of the antipsychotic. Conclusions: This is the third case reported in the literature of a fatal outcome of clozapine-induced hepatotoxicity.

The Effect of Tonsillectomy and Adenoidectomy on Upper Airway Obstruction Patterns in Children with Obstructive Sleep Apnea

Abstract Introduction Alterations in upper airway flow dynamics and sites of airway obstruction immediately after tonsillectomy and adenoidectomy (TA) have not been assessed. Identification of the changes in airway obstruction patterns after TA potentially improves the surgical management of children with obstructive sleep apnea (OSA). Objectives To evaluate the effect of TA on upper airway obstruction patterns detected with drug-induced sleep endoscopy (DISE). Methods The medical records of patients who underwent pre-TA DISE during the induction of anesthesia and post-TA DISE at the end of TA were reviewed. Data pertaining to polysomnography and DISE findings were analyzed. Results Twenty-seven patients (15 male and 12 females aged between 2 and 18 years old) were identified. All patients had obstruction at multiple sites of the upper airway. Prior to TA, airway obstruction was at the level of the velum in 27 patients, of the oropharynx/lateral walls in 27, of the tongue in 7, and of the epiglottis in 4. After TA, airway obstruction was at the level of the velum in 24 patients, of the oropharynx/lateral walls in 16, of the tongue in 6, and of the epiglottis in 4. The degree of obstruction at the levels of the velum and oropharynx/lateral walls after TA was significantly decreased. Conclusions Drug-induced sleep endoscopy performed prior to TA revealed that most of the sites of airway obstruction persisted after TA in OSA children with multiple sites of airway obstruction. Further studies in larger group of children with OSA are needed to establish the value of DISE findings in predicting residual OSA after TA, surgical planning, determining the need for post TA sleep study, and counseling caregivers.

Clinician's dilemma: Naproxen-induced liver injury

Naproxen is a widely used nonsteroidal anti-inflammatory drug (NSAID) in pediatric population, used for mild-to-moderate pains, arthritis, and other immune-mediated disorders. It rarely causes clinically apparent liver injury in the adult population taking high doses of the drug over a prolonged period and is reported even rarer in pediatric population. We present a case of drug-induced liver injury (DILI) in a 13-year-old girl taking naproxen in therapeutic doses for juvenile rheumatoid arthritis. There was a complete recovery of liver function following discontinuation of naproxen therapy.

Uso del esquema Scottish and Newcastle Anti-Emetic Pretreatment (SNAP) en la recuperación de una intoxicación por sobredosis masiva de acetaminofén (paracetamol) con injuria hepática aguda - Reporte de caso

Acetaminophen is a drug widely used in the world and easily accessible due to its antipyretic, analgesics characteristics, among others (1); however, exposure to toxic doses causes organic damage and even death. We present the case of an 18-year-old female patient who ingested 40 grams of acetaminophen and developed severe liver dysfunction, being treated with N-acetylcysteine (NAC) antidotal therapy according to the simplified scheme: Scottish and Newcastle Anti-emetic Pretreatment Paracetamol Poisoning Study Regimen (SNAP), presenting improvement in the clinical course and decrease in liver profiles, coagulation disorder, INR and resolution of the condition.

El acetaminofén es un fármaco ampliamente usado en el mundo y de fácil acceso por sus características antipiréticas, analgésicas, entre otras (1); sin embargo la exposición a dosis tóxicas produce daños a nivel orgánico e incluso la muerte. Presentamos el caso de una paciente mujer de 18 años que ingirió 40 gramos de acetaminofén y desarrolló injuria hepática severa, siendo tratada con terapia antidotal de N-acetilcisteína (NAC) según el esquema simplificado: Scottish and Newcastle Anti-Emetic Pretreatment Paracetamol Poisoning Study Regimen (SNAP), presentando mejoría del curso clínico y disminución de los perfiles hepáticos, trastorno de coagulación, INR y resolución del cuadro.

Development and application of drug-induced liver injury surveillance and assessment system / 中国药房

OBJECTIVE To establish the drug-induced liver injury （DILI） surveillance and assessment system （DILI-SAS）， and to improve the diagnostic efficiency of clinical DILI. METHODS The DILI-SAS was constructed by using natural language processing technology to mine and utilize all inpatient medical record data， and combined with Roussel Uclaf causality assessment method （RUCAM）. The medical records of 19 445 hospitalized patients from August 2022 to January 2023 were detected to verify the performance of the system and manually analyze the basic data of patients with DILI and the distribution of the first suspected drugs. RESULTS The overall accuracy rate of the DILI-SAS system was 91.95%， and the recall rate was 93.20%. Seventy-five DILI cases were detected， and the DILI incidence rate was 385.70/100 000 people. The efficiency of DILI monitoring by human- computer coupling was increased by about 60 times of manual monitoring； males （61.33%） and patients over 60 years old （56.00%） were the most common in the 75 cases of DILI. The clinical type of liver injury was hepatocyte injury （69.33%）， the incubation period was mainly 5-90 days after treatment （62.67%）， and the RUCAM score between 3 and 5 was the most common （66.67%）； pharmacological distribution of the first suspected drugs was mainly dihydropyridines， HMG CoA reductase inhibitors， proton pump inhibitors， etc. The specific drugs were atorvastatin， omeprazole， ceftriaxone， metronidazole and other drugs. CONCLUSIONS The establishment of DILI-SAS can improve the evaluation efficiency on the basis of ensuring the accuracy degree， and provide a solution for the early identification， diagnosis and evaluation of clinical DILI.

Clinical analysis of 202 patients with drug-induced liver injury / 中国基层医药

Objective:To investigate the clinical characteristics of drug-induced liver injury and provide a theoretical basis for the prevention and treatment of drug-induced liver injury.Methods:The clinical data of 202 patients with complete information on drug-induced liver injury who received treatment in First Hospital of Shanxi Medical University from November 2018 to November 2021 were collected. The information including gender, age, type and name of drugs taken or exposed, clinical characteristics, autoantibodies, and liver function was statistically analyzed.Results:Among the 202 patients with drug-induced liver injury, 77 patients (38.1%) were male and 125 patients (61.9%) were female. Age distribution was mainly at > 40-60 years. There were 141 cases (69.8%) of hepatocellular type, 27 cases (13.4%) of cholestatic type, and 34 cases (16.8%) of mixed type. There were statistically significant differences in alanine aminotransferase, aspartate aminotransferase, γ-glutamine transferase, alkaline phosphatase, prothrombin time, international standardized ratio, and prothrombin activity between different clinical types ( H = 91.43, 58.65, 9.25, 32.69, 9.56, 8.19, 9.40, all P < 0.05). Among the 202 patients with drug-induced liver injury, severe liver injury occurred in the largest proportion of cases (40.6%). There was no significant difference in the disease severity between different clinical types ( P = 0.789). The top three types of drugs causing liver injury were traditional Chinese medicine [52.0% (105/202)], antineoplastic drugs [6.4% (13/202)], and antipsychotics [5.9% (12/202)]. The detection rate of autoantibodies in 202 patients with drug-induced liver injury was 29.7% (60/202). Conclusion:Drug-induced liver injury lacks specificity in clinical manifestations. A wide variety of drugs can cause liver injury. Clinicians should strengthen liver function monitoring in key populations. The proportion of patients with mixed-type liver failure is high, which should be taken seriously. When patients with drug-induced liver injury are positive for liver disease-related antibodies, clinicians should be vigilant about the possibility of drug-induced liver injury.

Retrospective study on the use of epinephrine in patients with drug-induced anaphylactic shock in Chongqing from 2015 to 2022 / 中国药房

OBJECTIVE To evaluate the rationality of epinephrine in the treatment of drug-induced anaphylactic shock， and to provide a reference for further standardizing the treatment measures of anaphylactic shock. METHODS According to the relevant data of the reports of severe adverse drug reaction （ADR） of drug-induced anaphylactic shock provided by Chongqing ADR Monitoring Center from 2015 to 2022， the selection of treatment drugs， and the application of epinephrine in anaphylactic shock were analyzed retrospectively； the clinical outcomes of anaphylactic shock with different epinephrine administration methods were investigated. RESULTS A total of 1 415 cases of severe ADR related to drug-induced anaphylactic shock were reported， with a male-to-female ratio of 1.04∶1； the drugs that caused allergic shock mainly included anti-infective drugs （47.92%）， TCM injections （9.12%）； the patients who suffered from drug-induced anaphylactic shock within 10 min after medication accounted for 43.96%； 97.24% of patients were cured or improved， and 2.76% of patients died or did not been improved. Among 1 415 patients， 63.39% of patients were treated with epinephrine， and the patients who preferred epinephrine treatment accounted for 53.14%； the intramuscular injection， subcutaneous injection， intravenous injection and intravenous drip accounted for 33.78%， 30.32%， 25.75% and 1.23%， respectively. The initial dose range of epinephrine was 0.01-10 mg， and the most frequent single dose was 1 mg （44.70%）. Excessive single doses of intramuscular injection， subcutaneous injection and intravenous injection accounted for 51.03% （148 cases）， 53.13% （136 cases） and 91.47% （193 cases） respectively， and the risk of overdose in intravenous injection was higher （P＜0.05）. The patients receiving initial treatment with epinephrine had a higher improvement rate/cure rate than those who did not use epinephrine （98.14% vs. 96.23%， P＝0.029）； the patients who preferred epinephrine had a higher improvement rate/cure rate than those who did not preferred epinephrine （98.14% vs. 95.17%， P＝0.031）； the improvement rate/cure rate of patients receiving intramuscular injection of epinephrine was higher than those without intramuscular injection （99.01% vs. 96.69%， P＝0.038）. CONCLUSIONS There are some unreasonable phenomena in the treatment of drug-induced anaphylactic shock， such as inappropriate selection of drugs， insufficient use of epinephrine， delay of administration， inappropriate route of administration and excessive single dose.

Chinese guideline for diagnosis and management of drug-induced liver injury (2023 version) / 中华肝脏病杂志

Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, anti-neoplastic drugs), and signal and assessment of DILI in clinical trials.

Advances in clinical research on drug-induced acute interstitial nephritis / 中国临床药理学与治疗学

The kidneys are one of the main excretory organs for drugs and when drugs are not excreted effectively, they can accumulate in the kidneys or in the interstitial tubules, leading to drug-induced kidney injury. The tubulointerstitium accounts for 80% of the volume of the kidney and is the primary site of response to various types of renal injury. This article focuses on drug-induced acute interstitial nephritis, highlighting its clinical symptoms, listing common induction drugs, analysing pathological features, and explaining its pathogenesis from the perspective of immune response, with the aim of providing a basic and clinical evidence for subsequent studies.

Drug-induced dysphagia risk in elder people——A pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) database / 中国临床药理学与治疗学

AIM: To evaluate the risk of drug-related dysphagia in elder people based on the FDA Adverse Event Reporting System (FAERS). METHODS: We collected the reports of dysphagia in elder people (Age≥65) from 2004 quarter 1 through 2022 quarter 2 of FAERS by Open Vigil 2.1 database. The reported odds ratio (ROR) and the proportional reported ratio (PRR) were calculated to detect the adverse reaction signal of drug-induced dysphagia in elder people. Signal generation standard of ROR: number of reports≥3 with the lower limit of 95% confidence interval (CI) of the ROR value>1, PRR≥2 and c

Research progress on mechanism of tyrosine kinase inhibitor-induced liver injury / 中国药理学通报

Tyrosine kinase inhibitors (TKIs) are a class of molecular targeted drugs that inhibit the activation of downstream signaling pathways by inhibiting oncogene-related receptor tyrosine kinases to exert anti-cancer effects. TKIs are superior to traditional chemotherapeutics in terms of selectivity, effectiveness and safety, and are widely used in the treatment of cancer. However, TKIs-induced liver injury is one of the difficult problems in its clinical application. In this article, relevant literatures from domestic and abroad are reviewed and the research progress in the classification, clinical application of TKIs and the mechanism of TKIs-induced liver injury are summarized. This review intends to provide a reference for further elucidating the mechanism of TKIs-induced liver injury, and seeking effective prevention and treatment methods.

Exploration on "Efficacy-toxicity" Association Mechanisms of Tripterygium wilfordii Polyglycoside Tablets Against Rheumatoid Arthritis Based on Multi-omics Integrated Regulatory Network / 中国实验方剂学杂志

ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets （TWPT） by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis （RA） and TWPT-induced liver injury. MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts， the "efficacy-toxicity" association network of TWPT was constructed， and the key network targets were identified by calculating the topological values of the nodes， including the degree， closeness and betweenness. After that， the biological functions and pathways of the key network targets were investigated by enrichment analysis. ResultA total of 119 differentially expressed genes （58 up-regulated and 61 down-regulated） between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics， and 49 differentially expressed proteins （36 up-regulated and 13 down-regulated） were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition， the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine， and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore， the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically， the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance， especially playing an important role in neutrophil degranulation， complement cascade reaction， and immune-inflammatory response mediated by protein post-translational modification. Notably， the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation， such as RAS and mitogen-activated protein kinase （MAPK） signaling pathway， and in several liver functional processes， such as glycogen metabolism and redox reaction. ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics， transcriptomics and proteomics， laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.