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.

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.

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.

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.

Identification of Q-markers for Schisandrae Sphenantherae Fructus in treating drug-induced liver injury based on network pharmacology, fingerprint and quantitative analysis / 中国中药杂志

This study aims to establish the ultra-performance liquid chromatography(UPLC) fingerprint and multi-indicator quantitative analysis method for Schisandrae Sphenantherae Fructus(SSF) and to screen out the potential quality markers(Q-markers) of hepatoprotection based on network pharmacology. The similarity analysis was performed using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System, which showed that the similarity of the fingerprints of 15 samples from different regions ranged from 0.981 to 0.998. Eighteen common components were identified, from which 3 differential components were selected by cluster analysis and principal component analysis. The "component-target-pathway" network was built to predict the core components related to the hepatoprotective effects. Fourteen core components were screened by network pharmacology. They acted on the targets such as AKT1, CCND1, CYP1A1, CYP3A4, MAPK1, MAPK3, NOS2, NQO1, and PTGS2 to regulate the signaling pathways of lipid metabolism and atherosclerosis, hepatitis B, interleukin-17, and tumor necrosis factor. Considering the chemical measurability, characteristics, and validity, schisantherin A, anwulignan, and schisandrin A were identified as the Q-markers. The content of schisantherin A, anwulignan, and schisandrin A in the test samples were 0.20%-0.57%, 0.13%-0.33%, and 0.42%-0.70%, respectively. Combining the fingerprint, network pharmacology, and content determination, this study predicted that schisantherin A, anwulignan, and schisandrin A were the Q-markers for the hepatoprotective effect of SSF. The results can provide reference for improving the quality evaluation standard and exploring the hepatoprotective mechanism of SSF.

Lesión hepática inducida por consumo de Valeriana officinalis y Passiflora incarnata, reporte de caso / Hepatic injury induced by the consumption of Valeriana officinalis and Passiflora incarnata, a case report

Los medicamentos homeopáticos y fitoterapéuticos que contienen productos herbarios son cada vez más utilizados, sin embargo, se desconoce el potencial de efectos adversos por parte de los usuarios y personal sanitario. Se reporta el caso de una mujer de 34 años quien consulta por dolor abdominal y náuseas, con alteraciones al ingreso de función hepática con patrón hepatocelular, se descartaron múltiples etiologías y se consideró que pudiera ser lesión hepática medicamentosa secundaria al consumo de medicamentos desde hacía una semana para dismenorrea, y a fitoterapéuticos que consumía de forma crónica, los cuales se suspendieron. A los doce días de su egreso, reingresó por sintomatología similar; se documentó nuevamente perfil hepático con patrón hepatocelular. Al reinterrogatorio, la paciente comentó la ingesta crónica de Valeriana officinalis y Passiflora incarnata, que retomó al egreso hospitalario, por lo que luego de descartar diagnósticos diferenciales, se consideró que el cuadro era inducido por el consumo de dichos medicamentos. Durante la hospitalización se suspendió su consumo, con normalización del perfil hepático. Es importante que los consumidores estén informados sobre los riesgos potenciales de los productos herbarios, sus efectos por consumos prolongados y las implicaciones de la autoformulación.

Homeopathic and phytotherapeutic medicines containing herbal products are increasingly used, however the potential for adverse effects on users and healthcare personnel is unknown. We report the case of a 34-year-old woman who consulted for abdominal pain and nausea, accompanied by hepatocellular pattern on liver function tests. Multiple etiologies were ruled out and it was considered that it could be a drug-induced liver injury secondary to the consumption of medications she had been taking a week prior for dysmenorrhea, and phytotherapeutics that she had been taking for seve-ral years, which were all discontinued. Twelve days after her discharge, she was readmitted due to similar symptoms; a liver profile with a hepatocellular pattern was again documented. Upon further questioning, the patient mentioned a chronic intake of Valeriana officinalis and Passiflora incarnata, which she resumed upon discharge. After ruling out the differential diagnoses, it was concluded that the symptoms of the patient were induced by the consumption of these herbal products. During hos-pitalization, their consumption was suspended, with normalization of the liver profile. It is important that consumers are informed about the potential risks of herbal products, their effects from long-term use, and the implications of self-medication.

Manifestaciones hepatobiliares asociadas a la enfermedad inflamatoria intestinal / Hepatobiliary manifestations associated with inflammatory bowel disease

La enfermedad inflamatoria intestinal (EII) engloba dos entidades, la enfermedad de Crohn (EC) y la colitis ulcerativa (CU), las cuales son enfermedades inmunomediadas, crónicas y recurrentes que, aunque afectan al intestino, pueden ir acompañadas de manifestaciones extraintestinales de tipo hepatobiliar en el 5 % de los casos. Entre ellas, las más frecuentes son la enfermedad por hígado graso no alcohólico (EHGNA), la colelitiasis, la colangitis esclerosante primaria (CEP), la colangitis relacionada con IgG4, la hepatitis autoinmune (HAI), el síndrome de superposición HAI/CEP, así como la lesión hepática inducida por fármacos (DILI); y otras menos frecuentes como la colangitis biliar primaria (CBP), la trombosis de la vena porta, los abscesos hepáticos, la hepatitis granulomatosa, las hepatitis B y C, la reactivación de la hepatitis B por terapia inmunosupresora, y la amiloidosis. Estas manifestaciones hepatobiliares cursan con una fisiopatología similar o inclusive la misma de la EII, en la que participan el sistema inmune innato y adaptativo, alteración de la microbiota (disbiosis), permeabilidad intestinal, factores de riesgo genéticos (comunes para EII y manifestaciones hepatobiliares) y desencadenantes ambientales. La primera manifestación de un trastorno hepatobiliar es la alteración del perfil de función hepática, por lo que el abordaje diagnóstico se debe dirigir a evaluar y monitorizar las enzimas hepáticas y su asociación a algún patrón diferencial de alteración hepatocelular o colestásico, con el fin de tomar decisiones oportunas con respecto a la suspensión, indicación o modificación de algún medicamento, o cualquier otro abordaje que impida o retrase la evolución de la enfermedad hepatobiliar, y al mismo tiempo garantice el control de la EII, mejorando potencialmente el pronóstico de estos pacientes.

Inflammatory bowel disease (IBD) encompasses two entities, Crohn's disease (CD) and ulcerative colitis (UC), which are chronic, recurrent, immune-mediated inflammatory diseases that, although affect the gut, may be accompanied by extraintestinal hepatobiliary manifestations in 5% of the cases. Among them, the most frequent are non-alcoholic fatty liver disease (NAFLD), cholelithiasis, primary sclerosing cholangitis (PSC), IgG4-related cholangitis, autoimmune hepatitis (AIH), AIH/PSC overlap syndrome, as well as drug-induced liver injury (DILI); and other less frequent such as primary biliary cholangitis (PBC), portal vein thrombosis, liver abscesses, granulomatous hepatitis, hepatitis B and C, reactivation of hepatitis B due to different drugs, and amyloidosis. These hepatobiliary manifestations present with a pathophysiology similar or even the same as that of IBD, where several factors participate, including the innate and adaptive immune system, an interaction with the components of the microbiota, leaky gut, genetic risk factors (common for both IBD and hepatobiliary manifestations) and environmental triggers. The first manifestation of a hepatobiliary disorder is the alteration of the liver profile; therefore, the diagnostic approach should be aimed at evaluating and monitoring liver enzymes and their association with some differential pattern of hepatocellular or cholestatic changes, in order to make appropriate decisions regarding the suspension or modification of any medication, or any other approach that prevents or delays the evolution of hepatobiliary disease, and at the same time guarantees control of IBD, improving the prognosis of these patients.

Reviewing the Compounding Risks for Tuberculosis DrugInduced Liver Injury in a Patient with Transfusion Dependent Thalassaemia

@#A patient presents with jaundice three weeks into commencement of anti-tuberculosis therapy (ATT). Tuberculosis drug-induced liver injury (TB-DILI) is a main concern in patients commencing ATT. Studies have reported various risk factors associated with TB-DILI, urging vigilance in monitoring liver enzymes in these patients. We aim to review the causes of jaundice in a patient with transfusion dependent thalassaemia commenced on ATT and highlight the risk factors associated with TB-DILI.

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.

Statin-related drug-induced liver injury / 中华肝脏病杂志

Statins are a kind of prescription drug that is widely used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic diseases. A common side effect of statin use is a mild rise in liver aminotransferases, which occurs in less than 3% of patients. Statin-related liver injury is most commonly caused by atorvastatin and simvastatin, but severe liver injury is uncommon. Therefore, understanding and evaluating hepatotoxicity and weighing the benefits and risks is of great significance to better realize the protective effect of statins.

Genetic susceptibility to drug-induced liver injury / 中华肝脏病杂志

Drug-induced liver injury (DILI) risk prediction, diagnosis establishment, clinical management, and all other aspects are facing great challenges. Although the current understanding of its pathogenesis is still incomplete, research over the past 20 years has shown that genetic susceptibility may play an important role in the occurrence and development of DILI. In recent years, pharmacogenomics studies have further revealed the association between human leukocyte antigen (HLA) genes, some non-HLA genes, and hepatotoxicity from certain drugs. However, due to the lack of well-designed, prospective, large-sample cohort validation and low positive predictive values, there may still be some way to go before the current results can be truly translated into clinical practice for precise prediction and prevention of DILI risk.

Advances in clinical diagnosis and treatment of drug-induced liver injury in children / 中华肝脏病杂志

Drug-induced liver injury (DILI) is one of the most common adverse drug reactions that may seriously threaten the health of children and is receiving increasing clinical attention day by day. There is still no independent diagnosis and treatment guideline for DILI in children, but its clinical features are not completely similar to those in adults. This article reviews the epidemiology, clinical features, diagnosis, and treatment progress in order to provide a reference for the management of DILI in children.

Comparative analysis of clinical diagnosis and treatment guidelines for drug-induced liver injury at home and abroad / 中华肝脏病杂志

Drug-induced liver injury influencing factors are complex and have diverse clinical manifestations. Simple and reliable diagnostic methods are still deficient, and further classification of toxicological mechanisms is required. There are numerous pertinent discrepancies between domestic and international guidelines aimed at drug-induced liver injury diagnosis and treatment, with partial to no consensus on the content. The American Gastroenterological Association's 2021 Clinical Guidelines, the Asia-Pacific Association for the Study of the Liver's 2021 Consensus Guidelines, the Council for International Organizations of Medical Sciences' 2020 International Consensus, the European Society's Hepatology Committee's 2019 Clinical Practice Guidelines, and the 2015 Chinese Medical Association Guidelines are five influential clinical guidelines on drug-induced liver injury at home and abroad. The epidemiology, risk factors, diagnosis and evaluation, treatment management, and other contents, particularly traditional Chinese medicine, were compared and analyzed using other relevant consensus opinions or guidelines in order to improve understanding and provide a reference for clinical diagnosis and treatment of drug-induced liver injury.

Significance of histological assessment in drug-induced liver injury / 中华肝脏病杂志

Liver histological assessment is of great clinical significance for the diagnosis, classification, and prognosis prediction of drug-induced liver injury (DILI). Liver histological evaluation can effectively supplement RUCAM. The clinical phenotypes of DILI are complex and diverse, including acute, chronic and severe hepatic injury. DILI has multiple insult-targets, including hepatocytes, cholangiocytes, and vascular endothelial cells and others. The pathological damage patterns are similar to many types of non-DILI liver diseases, therefore making differential diagnosis difficult. New anti-tumor drugs such as immune checkpoints inhibitors and targeted therapy are widely used in clinical antineoplastic practice, thus the growing incidence of related liver injury occurs. Liver histological examination can effectively assess the pathological phenotypes and severity of DILI, so as to guide treatment. In uncommon conditions such as special types of DILI (such as hepatic vascular disease), DILI with other competitive etiology overlapping, chronic DILI, and DILI induced liver failure, liver histological assessment can provide strong support for identifying the cause, rational treatment, and prognosis. Currently, the histological evaluation system for drug-induced liver injury seems to be a lack of consensus, and the diagnosis of DILI is short of highly specific and sensitive serological markers. All in all, liver histological assessment plays a crucial role in the diagnosis and differential diagnosis of DILI.