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La hepatotoxicidad inducida por medicamentos es un diagnóstico de descarte. Típicamente, se presenta en pacientes que desarrollan cambios clínicos y bioquímicos compatibles con hepatitis, pero relacionados con el inicio reciente de agentes farmacológicos, y que se resuelven tras el retiro de la noxa. Su desarrollo se ha descrito con el uso de algunos antibióticos, antituberculosos, estatinas, herbolarios y antiinflamatorios no esteroideos; sin embargo, hay pocos reportes de casos con el uso de anticonceptivos orales, en los cuales el surgimiento de mecanismos idiosincráticos puede llevar a la presentación de características clínicas como ictericia y anormalidades en los exámenes de laboratorio, como la elevación de las transaminasas. Esto requiere de estudios extensos para descartar otras patologías que pueden presentarse de esta forma, lo que representa un reto clínico. En este artículo se muestra el reporte de un caso de una paciente con antecedente de uso crónico de anticonceptivos implantables y que, tras el ajuste de la terapia con el inicio de anticonceptivos orales, desarrolla un episodio de elevación marcada de transaminasas e ictericia.
Drug-induced liver injury is a rule-out diagnosis. Typically, it occurs in patients who develop clinical and biochemical changes compatible with hepatitis, but related to a history of recent onset of pharmacological agents, and resolves after withdrawal of the noxious substances. Its development has been described with the use of some antibiotics, antituberculosis agents, statins, herbal and nonsteroidal anti inflammatory drugs; however, there are few reports of cases with the use of oral contraceptives, in which the appearance of idiosyncratic mechanisms can lead to the presentation of clinical features such as jaundice and laboratory tests abnormalities, like transaminase elevation, requiring extensive studies to rule out other pathologies that may have this clinical presentation, wich represents a clinical challenge. We present a case report of a patient who had chronic use of implantable contraceptives and who, after adjustment of therapy with the start of oral contraceptives, developed an episode of marked elevation of transaminases and jaundice.
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Tanto la lesión hepática inducida por drogas (DILI), así como la lesión hepática inducida por hierbas (HILI), son una preocupación creciente en la atención sanitaria contemporánea que plantea importantes desafíos clínicos debido a sus variadas etiologías, presentaciones clínicas y posibles resultados potencialmente mortales. Presentamos el caso de un paciente masculino de 38 años con antecedentes de cálculos renales que consultó por dolor lumbar y hematuria. Al ingreso presentó ictericia, hepatomegalia, dolor a la palpación en fosa ilíaca derecha y no tenía signos de hepatopatía crónica, con pruebas de función hepática anormales, que mostraron un patrón hepatocelular asociado con hiperbilirrubinemia. Se descartó obstrucción biliar, trombosis portal, hepatitis autoinmune y viral, con panel autoinmune negativo. El paciente refirió haber consumido un remedio herbario para los cálculos renales llamado "vino rompe cálculos (chancapiedra)", que se supone contiene Phyllanthus niruri, cinco días antes del inicio de los síntomas. Una biopsia hepática reveló hepatitis aguda con infiltrado inflamatorio mixto. Debido al empeoramiento de las pruebas de función hepática y la sospecha de DILI idiosincrásico, se inició un ensayo terapéutico con corticosteroides, que resultó en una mejoría clínica y del perfil hepático. La gravedad de este caso nos recuerda la necesidad de incrementar el seguimiento por parte de las autoridades reguladoras de medicamentos, implementar campañas educativas para los pacientes e informar a la comunidad sobre productos con alertas activas.
Both drug-induced liver injury (DILI) and herb-induced liver injury (HILI) are a growing concern in contemporary healthcare that poses significant clinical challenges due to their varied etiology, clinical presentations, and potential life-threatening outcomes. We present the case of a 38-year-old male patient with a history of kidney stones who consulted for low back pain and hematuria. On admission he presented with jaundice, hepatomegaly, pain on palpation in the right iliac fossa and no signs of chronic liver disease, with abnormal liver function tests, which showed a hepatocellular pattern associated with hyperbilirubinemia. Biliary obstruction, portal thrombosis, autoimmune and viral hepatitis were ruled out, with negative autoimmune panel. The patient reported consuming an herbal remedy for kidney stones called "stone-breaking wine (chancapiedra)", presumed to contain Phyllanthus niruri, five days before the onset of symptoms. A liver biopsy revealedacute hepatitis with mixed inflammatory infiltrate. Due to worsening liver function tests and suspicion of idiosyncratic DILI, a therapeutic trial with corticosteroids was initiated, which resulted in clinical and liver profile improvement. The severity of this case reminds us of the need to increase follow-up by drug regulatory authorities, implement educational campaigns for patients, and inform the community about products with active alerts.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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@#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.
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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.
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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.
Subject(s)
Humans , Chemical and Drug Induced Liver Injury/therapy , Drug-Related Side Effects and Adverse Reactions , Liver Failure, Acute , Dietary Supplements/adverse effects , Risk FactorsABSTRACT
Objective To investigate the clinical, biochemical, pathological, disease course, and prognostic features of drug-induced liver injury (DILI) patients with different types of bile duct injury. Methods Four patients who were diagnosed with bile duct injury-type DILI by liver biopsy in Shijiazhuang Fifth Hospital, from March 2015 to October 2010 were selected, and related data were collected, including clinical data, laboratory examinations, radiological examination, and prognosis.The semi-quantitative score was determined for liver pathological morphology, and each indicator was compared between the four patients. Results Bile duct injury-type DILI was more common in female patients, and most patients tended to have a good prognosis.Clinical symptoms, liver biochemical parameters, and prognosis varied with the site, grade, scope, regeneration, and repair of bile duct injury. Conclusion Liver biopsy is still the gold standard for making a definite diagnosis of bile duct injury-type DILI, understanding the condition of lesions, and judging the prognosis of this disease.
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Objective To investigate the clinical features of patients with drug-induced liver injury (DILI). Methods A retrospective analysis was performed for the clinical data of 1 376 patients with DILI who were admitted to 20 hospitals in Shaanxi Province, China, from 2009 to 2019 and were diagnosed with RUCAM scale as the diagnostic criteria, and these patients were analyzed in terms of sex, age, underlying diseases, suspected drugs causing DILI, clinical manifestations, laboratory examination, treatment process, and prognosis. The t -test and Wilcoxon test were used for comparison of continuous data between two groups, the chi-square test was used for comparison of categorical data between groups, and the Kruskal-Wallis H rank sum test was used for comparison of ordered polytomous data between groups. Results Among the 1 376 patients, there were 577(41.93%) male patients and 799 (58.07%) female patients, with a male/female ratio of 0.72:1. As for different age groups, the 40-60 years group had a higher incidence rate and accounted for 44.77%, and there was a significant difference in sex distribution between different age groups ( χ 2 =20.784, P =0.008). As for the three clinical types, there was no significant difference in incidence rate between men and women ( χ 2 =1.409, P =0.494), and there was a significant difference in the distribution of clinical types between different age groups ( χ 2 =47.025, P 0.05). Conclusion There is a high incidence rate of DILI in women and middle-aged and elderly people, and traditional Chinese medicine is the leading cause of DILI. Patients with different clinical types tend to have different prognoses, with a good overall prognosis.
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BackgroundIn order to implement the spirit of the 20th National Congress of the Communist Party of China， and the Opinions on Promoting the Inheritance， Innovation and Development of Traditional Chinese Medicine（TCM）， to regularly summarize the research results of TCM， to present the academic progress of TCM dynamically， and to give full play to the academic leadership of academic groups， the China Association of Chinese Medicine had organized the selection of the top 10 academic progress of TCM in 2022. The selection work adhered to the four orientations， eliminated the four only， highlighted the solution of clinical problems， answered scientific questions， led the development of the industry， reflected the exploratory and forward-looking， innovative and breakthrough， focused on new laws， new discoveries， new methods， new products， new theories in the field of basic research and applied basic research in TCM. After dynamic collection， preliminary examination， review and final judgment， the top 10 academic progress of TCM in 2022 were determined.
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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.
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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.
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Objective To investigate whether Toll-like receptor 4 (TLR4) inhibition affects liver regeneration during acetaminophen (APAP)-induced liver injury in mice, as well as the mechanism of TLR4 involved in liver regeneration. Methods A total of 78 male CD-1 mice were divided into nine groups using a random number table, i.e., three control groups (normal control group, solvent control group, inhibitor control group) with 6 mice in each group and six experimental groups (APAP 24-hour group, TAK-242+APAP 24-hour group, APAP 48-hour group, TAK-242+APAP 48-hour group, APAP 72-hour group, TAK-242+APAP 72-hour group) with 10 mice in each group. The mice in the experimental groups were given a single dose of intraperitoneally injected APAP (300 mg/kg), and TAK-242 was intraperitoneally injected at a dose of 3 mg/kg at 3 hours before APAP administration. Serum and liver tissue samples were collected at different time points. The biochemical method was used to measure the serum level of alanine aminotransferase (ALT); HE staining was used to observe liver pathological changes; RT-PCR, Western blot, and immunohistochemistry were used to measure the expression levels of Cyclin D1, PCNA, Ki-67, STAT3, and p-STAT3. The t -test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups. Results Compared with the normal control group, the APAP 24-hour and 48-hour groups had a significantly higher serum level of ALT (both P < 0.05), and the TAK-242+APAP 24-hour and 48-hour groups had a significantly higher serum level of ALT than the APAP group at the same time point (both P < 0.05). HE staining showed typical central lobular necrosis in the liver of APAP-treated mice, and the TAK-242+APAP 24-hour and 48-hour groups had a significantly larger necrotic area than the APAP group at the same time point (both P < 0.05). RT-PCR, Western blot, and immunohistochemistry showed that the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had significantly lower mRNA and protein expression levels of Cyclin D1 than the APAP group at the same time point (all P < 0.05); the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had a significantly lower mRNA expression level of PCNA than the APAP group at the same time point (all P < 0.05), and the TAK-242+APAP 24-hour and 48-hour groups had a significantly lower protein expression level of PCNA than the APAP group at the same time point (all P < 0.05); the TAK-242+APAP 24-hour and 72-hour groups had a significantly lower mRNA expression level of Ki-67 than the APAP group at the same time point (all P < 0.05), and the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had a significantly lower protein expression level of Ki-67 than the APAP group at the same time point (all P < 0.05). In addition, the TAK-242+APAP 24-hour and 48-hour groups had a significantly lower phosphorylation level of STAT3 than the APAP group at the same time point (both P < 0.05). Conclusion TLR4 may promote liver regeneration by increasing the phosphorylation level of STAT3 during APAP-induced liver injury in mice.
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Objective To investigate the value of total bilirubin rebound rate (TBRR), total bilirubin clearance rate (TBCR), and TBCR after 1 week of treatment (ΔTBCR) in evaluating the short-term prognosis of patients with severe drug-induced liver injury (DILI) after artificial liver support therapy. Methods A retrospective analysis was performed for 203 patients with severe DILI who received artificial liver support therapy in Tianjin Third Central Hospital from September 2013 to December 2021, and general information, biochemical parameters, and clinical classification were collected. The patients were divided into improved group and unhealed group according to the prognosis at discharge, and Model for End-Stage Liver Disease (MELD) score, TBRR, TBCR, and ΔTBCR were calculated. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic (ROC) curve was plotted to investigate the value of assessment indices in predicting the prognosis of patients, and the Kaplan-Meier method was used to investigate the difference in the length of hospital stay in the context of different assessment indices. Results Compared with the unhealed group, the improved group had significantly lower age ( t =-2.762, P < 0.05), white blood cell count ( Z =-3.184, P < 0.05), total bilirubin ( t =-2.809, P < 0.05), conjugated bilirubin ( t =-2.739, P < 0.05), international normalized ratio ( Z =-2.357, P < 0.05), MELD score ( t =-3.090, P < 0.05), and TBRR ( t =-4.749, P < 0.05), as well as significantly higher albumin ( t =2.198, P < 0.05), prothrombin time activity ( t =2.018, P < 0.05), TBCR ( t =2.166, P < 0.05), and ΔTBCR ( t =9.549, P < 0.05). MELD score, TBRR, TBCR, and ΔTBCR had an area under the ROC curve (AUC) of 0.656, 0.727, 0.611, and 0.879, respectively, and ΔTBCR had a better predictive value than TBRR ( Z =3.169, P =0.001 5). The optimal cut-off value was 22.5% for TBRR (with a sensitivity of 94.6% and a specificity of 45.2%) and 27.4% for ΔTBCR (with a sensitivity of 77.7% and a specificity of 86.5%). ΔTBCR showed a good predictive value in different clinicopathological types, with extremely high sensitivity (91.4%) and specificity (100.0%) in evaluating the treatment outcome of patients with mixed-type DILI after artificial liver support therapy. Conclusion TBRR and ΔTBCR have a higher value than MELD score in evaluating the short-term prognosis of patients with severe DILI after artificial liver support therapy, among which ΔTBCR has a higher predictive value.