Hepatotoxicity Research Articles

Safety and Tolerability of Nintedanib in Patients with Fibrosing Interstitial Lung Diseases: Post-marketing Data.

Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF), other forms of progressive pulmonary fibrosis (PPF), and systemic sclerosis-associated interstitial lung disease (ILD). We present global post-marketing safety data for nintedanib in these fibrosing ILDs. Data on adverse events in patients with fibrosing ILDs who were treated with nintedanib were collected via spontaneous reporting and solicited reporting in various studies (excluding clinical trials).Data were collected from 15 October 2014 (first regulatory approval) to 15 October 2023. Adverse events were coded using the Medical Dictionary for Regulatory Activities. Cumulative exposure to nintedanib was estimated using sales data. Cumulative exposure to nintedanib was 380,557 patient-years. Diarrhoea was reported at a rate of 227.5 per 1000 patient-years. Only 2.6% of diarrhoea events were reported as serious. Of 39,788 (33.6%) diarrhoea events with a known time to onset, almost 60% occurred within the first 3months of treatment. The rate of serious liver enzyme and bilirubin elevations (including drug-induced liver injury) was 4.0 per 1000 patient-years. Bleeding was reported at a rate of 24.2 per 1000 patient-years. Most (81.3%) bleeding events were non-serious. The rates of myocardial infarction, ischaemic stroke, and venous thromboembolism were 3.3, 3.3, and 2.0 per 1000 patient-years, respectively. Gastrointestinal perforation was reported at a rate of 0.9 per 1000 patient-years. Post-marketing safety data on established and potential adverse events associated with nintedanib in patients with fibrosing ILDs, collected over 9years, demonstrated a safety profile that was similar to that established in clinical trials and provided in the product labels. Education of patients about the adverse events that may be associated with nintedanib, and the effective management of adverse events when they occur, is important to minimise the impact of adverse events and help patients remain on treatment.

A novel immunopharmacological biocompound

The publication is devoted to topical issues of experimental study of new biocompounds, based on the creation of a consortium of biological composite compounds – biological active substances (metabiotics) produced by strains 59T and 60T of saprophytic compounds of the genus Bacillus subtilis. These strains are very promising for the creation of hepatopicts, new medicinal substances, in the creation and development of a new pharmacological class of hepatoprotectors. Previous studies have shown the safety and hepatoprotective effect of biologically active drugs. It is worth noting that the very effective compounds are the produced biologically active substances – metabolites of bacterial origin, on the basis of which it seems appropriate to create a new class of drugs – metabiotics. The absence of vegetative probiotic cells in such compounds will reduce the additional immune load on the body. The combined use of these compounds provides a potentiated pharmacological effect. In this regard, it seemed appropriate, under the conditions of modeling toxic liver damage by carbon tetrachloride, to conduct an experimental assessment of the immunotropic effect of biologically active substances (BAS) on laboratory animals in order to confirm the effect on cellular factors of immunity. The purpose of the study was to study the effect of the combined use of dietary supplements produced by Bacillus subtilis microorganisms on indicators of cellular immunity in laboratory animals with toxic liver damage. Acute toxic hepatitis was reproduced in white laboratory rats with repeated intragastric administration of carbon tetrachloride. The comparison drug was a registered hepatoprotective drug – ursosan. The immunotropic effect was assessed using factors such as: phagocytic activity of macrophages and neutrophils (FA), NBT test, quantitative assessment of antibody-forming cells, T and B lymphocytes. As a result of the studies performed, reliable data were obtained on an increase in the number of T and B lymphocytes, antibody-forming cells, as well as an increase in FA, which confirms the activation of all parts of cellular immunity in conditions of acute toxic liver damage. The data obtained allow us to recommend the studied biocompound for the creation of new drug candidates of microbiological origin, hepatoprotective agents with immunotropic effects.

Hepatocyte-Targeted Lipid Nanoparticle Delivery of HERC2 Plasmid Controls Drug-Induced Hepatotoxicity by Limiting β-Catenin-Regulated CYP2E1 Expression.

Understanding the molecular mechanisms that bridge hepatic inflammation and liver injury is crucial for developing effective therapeutic strategies for drug-induced liver injury (DILI) management. HECT domain and RCC1-like domain 2(HERC2) belongsto the large Herc family of ubiquitin E3 ligases, which are implicated in tissue development and inflammation. The observation reveals a pronounced HERC2 expression in specific hepatocyte subsets that proliferate in response to DILI in humans, prompting an investigation into the role of HERC2 in distinct DILI progression. Under the APAP challenge, liver-specific HERC2-deficient mice suffer more severe liver damage. Integrated single-cell RNA sequencing analysis unveils a negative correlation between HERC2 and CYP2E1, a vital metabolic enzyme for xenobiotics, in hepatocytes from APAP-challenged mice. Mechanistically, HERC2 interacts with β-catenin to promote its ubiquitination, thereby governing CYP2E1 transcriptional regulation. Targeted hepatic delivery of lipid nanoparticle-encapsulated HERC2-overexpressing plasmid markedly reduces liver damage caused by APAP overdose. Collectively, these findings elucidate a previously unrecognized protective role of HERC2 in protecting against acute liver injury associated with drug metabolism disorders, highlighting its potential as a therapeutic target in treating DILI.

Roles of NR1I3 and NR1H4 polymorphisms in the susceptibility to antituberculosis drug-induced liver injury in China: a case‒control study.

The pathogenesis of antituberculosis drug-induced liver injury (AT-DILI) remains largely unknown. The current investigation aimed to determine the genetic contribution of the nuclear receptor subfamily 1 Group I member 3 (NR1I3) and nuclear receptor subfamily 1 Group H member 4 (NR1H4) genes to the risk of AT-DILI in the Chinese population. A 1:4 matched case‒control study was conducted, and five single nucleotide polymorphisms (SNPs) in the NR1I3 and NR1H4 genes were detected and assessed. Utilizing a multivariate conditional logistic regression model, the effects of haplotype and genotype on the risk of AT-DILI were examined. Extended subgroup analysis was carried out based on sex. The distribution of the peak value of serum liver enzymes also compared among different genotypes. 224 AT-DILI cases and 896 controls were included in this study. No significant difference was observed in genotypes or haplotypes frequencies between AT-DILI cases and controls. However, comparisons of liver function indicators revealed significant differences in the peak values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) among patients with different genotypes of NR1H4 rs56163822 (GG vs. GT vs. TT, 27.1 U/L vs. 26.0 U/L vs. 23.0 U/L, p = 0.020; 34.0 U/L vs. 31.0 U/L vs. 30.6 U/L, p = 0.008; 15.5μmol/L vs. 15.0μmol/L vs. 13.7μmol/L, p = 0.029, respectively), as well as in the peak values of ALT and AST among male patients with different genotypes of NR1H4 rs56163822 (29.0 U/L vs. 26.9 U/L vs. 22.6 U/L, p = 0.002; 34.0 U/L vs. 32.0 U/L vs. 30.5 U/L, p = 0.019, respectively). Based on this 1:4 individual-matched case‒control study, the SNP rs56163822 in the NR1H4 gene may be linked to the susceptibility to AT-DILI in Chinese patients receiving anti-TB treatment. Further studies in larger varied populations are needed to validate our findings.

Comment on -Incidence and risk factors of antituberculosis drug-induced liver injury in India: A systematic review and meta-analysis.

Comment on -Incidence and risk factors of antituberculosis drug-induced liver injury in India: A systematic review and meta-analysis.

Evaluation of the efficiency of the hepatoprotector glucuronate in toxic hepatitis of various etiology

The objective was to study the effectiveness of the use of hepatoprotector glucuronate at the early stage of intensive therapy of toxic hepatitis of various etiologies.Materials and methods. We studied 120 patients with toxic hepatitis who were treated at the Republican research center for emergency medicine in 2022–2023. The study was carried out in two groups of patients. Group I – 60 patients admitted in 2023, who, in addition to traditional therapy, received a complex hepatoprotector glucuronate (Jetepar®)*. Group II (comparison group) – 60 patients who applied in 2022 and received only traditional therapy. Biochemical blood parameters were studied upon admission and over time on day 5. The severity of intellectual impairment was assessed using cognitive scales and the Reitan test on days 2 and 5 from the start of treatment.Results. Upon admission, both groups showed signs of toxic liver damage. In dynamics by the 5th day in patients of group I, there was a decrease in ALT by 63.7%, AST by 66.4%, alkaline phosphatase by 54.2% from the initial values, which was 3.9 and 2.6, 2. 1 lower than in the comparison group. The level of free ammonia in patients of group I on the 5th day decreased by 52%, and lactate by 57% from the initial level, almost to the physiological norm, while in the comparison group (II) only by 24.8% and 38.1%, which was 2.2 and 1.5 times worse than in the main group. Screening of the level of intelligence using two cognitive scales and the Reitan test showed that in patients in the comparison group, cognitive function indicators on the 5th day were 1.4, 1.5 and 1.2 times lower than in the main group.Conclusion. The use of the hepatoprotector glucuronate improves liver parameters and cognitive functions in patients with toxic hepatitis.

Refinement of Hy's Law using the Drug-Induced Liver Injury Network Database.

Hyman Zimmerman observed that hepatocellular (HC) drug-induced liver injury (DILI) with jaundice had a mortality rate of ≥10% (Hy's Law). Hy's Law does not specify the timing of liver tests nor the definition of HC DILI versus cholestatic or mixed (C/M) DILI. We aimed to assess the validity of Hy's Law in the prospective Drug-Induced Liver Injury Network (DILIN) cohort. Drugs with ≥10 confirmed DILI cases with jaundice were analyzed. Four permutations of Hy's Law were applied: R≥ 5 using initial (1) or peak (2) ALT, AST and Alk P levels, and the FDA associated criteria of ALT or AST ≥ 3x ULN with Alk P ≤ 2x ULN using initial (3) or peak values (4). Mortality was death or liver transplant adjudicated to be due to DILI. Using initial R values, mortality was 11.1% for HC vs 2.0% for C/M (p<0.001); using peak R values, mortality was 10.3% vs 1.6% (p<0.001). Using FDA associated definition, mortality was 7.9% vs 3.9% (p=0.04) using initial values and 7.9% vs 3.0% (p=0.01) using peak values. Using initial R values, drugs that frequently caused HC injury generally had mortality rates ≥ 10%; while drugs that typically caused C/M injury all had rates <10%. Occasional agents that caused HC injury with jaundice were associated with low mortality. Initial R values were the most reliable means of identifying Hy's Law cases. There were some drugs that caused HC injury with jaundice but with mortality rates <10%. Refinement of Hy's Law is warranted.

Improving the Diagnostic Accuracy of RECAM in North American Patients with Suspected Idiosyncratic Drug-Induced Liver Injury: Improving RECAM accuracy.

The RECAM is an updated, electronic version of the RUCAM to diagnose DILI. The primary aim of this study was to compare RECAM versus RUCAM in patients with suspected DILI. Patient encounters from 10/1/2015 to 9/30/2019 were searched for suspected DILI using ICD-10 K71 codes for toxic liver disease. DILIN expert opinion scores were assigned to each case (1/2/3= probable DILI, 4/5= non-DILI). RECAM and RUCAM scores were compared with DILIN expert opinion scores. Among 766,930 encounters searched, 120 unique patients met inclusion criteria with 72 (60%) adjudicated as probable-DILI. The most frequent suspect drugs were antimicrobials (38.3%), antineoplastics (8.3%), and antirheumatic drugs (8.3%). Mean age was 49.2 + 15.6 years and 50% were female with 45.8% having hepatocellular injury. RUCAM had better agreement with DILIN expert opinion for probable-DILI versus RECAM (66.7% vs. 44.4%, p=0.018). Both had 100% agreement with DILIN expert opinion for non-DILI. Frequently missing laboratory data included HCV RNA (64.3%) and anti-HEV IgM testing (70%), leading to loss of up to 6 points in RECAM scoring but not impacting RUCAM scores. A modified RECAM that made HCV RNA and anti-HEV IgM optional had better agreement with DILIN expert opinion compared to RUCAM (79.2% vs. 66.7%, p=0.09). Among 120 suspected DILI cases, RUCAM had better agreement with DILIN expert opinion scores versus RECAM. Making HCV RNA and anti-HEV IgM testing optional significantly improved agreement between RECAM and DILIN expert opinion. Future modifications to RECAM are needed to improve causality assessment in North American patients with suspected DILI.

Drug-induced liver injury associated with pretomanid, bedaquiline, and linezolid: Insights from FAERS database analysis.

The emergence of drug-resistant tuberculosis has necessitated novel treatments like the pretomanid, bedaquiline and linezolid (BPaL) regimen. This study investigated the association of drug-induced liver injury (DILI) with the BPaL regimen compared to first-line antituberculosis drugs (isoniazid, rifampin, pyrazinamide and ethambutol [HRZE]). A retrospective pharmacovigilance analysis was conducted using data from the US Food and Drug Administration Adverse Event Reporting System database from July 2019 to June 2023. Disproportionality analysis was employed to calculate the reporting odds ratio (ROR) of DILI for each component of the BPaL regimen. Onset time and mortality rates of DILI across different regimens were also compared. We identified 1242 cases of BPaL-related DILI. Most cases occurred in individuals under 65 years of age (63.8%), with more male patients affected than females (51.4% vs 39.5%). The association between antituberculosis drugs and DILI was stronger for the HRZE regimen (ROR = 7.99, 95% confidence interval [CI] 7.74-8.25) than the BPaL regimen (ROR = 4.75, 95% CI 4.55-4.97). The median onset time for DILI was significantly shorter with the BPaL regimen (8days, interquartile range [IQR] 3-28) compared to the HRZE regimen (20 days, IQR 6-48) (P < .001). Additionally, the BPaL regimen was associated with a higher risk of death due to DILI compared to the HRZE regimen (14.1% vs 10.4%, P = .003). Although the BPaL regimen had a lower overall risk of DILI compared to the HRZE regimen, it was significantly associated with DILI, indicating a need for careful monitoring during treatment.

Erratum: Letter to the Editor: Scavenger receptor a is a major homeostatic regulator that restrains drug-induced liver injury.

Erratum: Letter to the Editor: Scavenger receptor a is a major homeostatic regulator that restrains drug-induced liver injury.

Disproportionality analysis of flutamide- or bicalutamide-induced liver injury with and without steroids by using the Japanese Adverse Drug Event Report database.

Although the mechanism underlying flutamide- or bicalutamide-induced liver injury may be immune related, the details remain unclear. If this mechanism is immune related, steroid use may be considered as a treatment option. Disproportionality analysis was conducted to evaluate the effect of concomitant steroid use on flutamide- and bicalutamide-induced liver injury. Male patients aged 20years or older who were receiving nonsteroidal anti-androgens from April 2004 to October 2023 were screened from the Japanese Adverse Drug Event Report database. Data on liver injury, age, weight, height, steroid use, obesity, hepatic stenosis, alcohol-related hepatic disorders, hepatitis B and C, and common drugs known to cause drug-induced liver injury were analyzed. Liver injury was defined by the Standardized Medical Dictionary for Regulatory Activities query index (code 20000006, version 27.0). Among 142,430 patients, 2,316 were administered nonsteroidal anti-androgens. Reports of liver injury were disproportionate depending on the agents used (reporting odds ratio [ROR], 1.29; 95% confidence intervals [CI], 1.13-1.46), especially among flutamide or bicalutamide users (flutamide: ROR, 6.09; 95% CI, 4.51-8.23; bicalutamide: ROR, 1.24; 95% CI, 1.05-1.48). Multivariable logistic regression analysis correlated steroid use with a lower risk of flutamide- or bicalutamide-induced liver injury (flutamide: odds ratio, 0.07; 95% CI, 0.01-0.52; bicalutamide: odds ratio, 0.45; 95% CI, 0.21-0.96). Our findings suggest that flutamide and bicalutamide may increase the risk of liver injury compared to enzalutamide, apalutamide, and darolutamide. Furthermore, our study indicated that steroid use could aid in the management of liver injury.

Hepatotoxicity of antipsychotics: an exploratory pharmacoepidemiologic and pharmacodynamic study integrating FAERS data and in vitro receptor-binding affinities.

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

Acacetin, a Natural Flavone with Potential in Improving Liver Disease Based on Its Anti-Inflammation, Anti-Cancer, Anti-Infection and Other Effects.

Liver disease is a global public problem, and the cost of its therapy is a large financial burden to governments. It is well known that drug therapy plays a critical role in the treatment of liver disease. However, present drugs are far from meeting clinical needs. Lots of efforts have been made to find novel agents to treat liver disease in the past several decades. Acacetin is a dihydroxy and monomethoxy flavone, named 5,7-dihydroxy-4'-methoxyflavone, which can be found in diverse plants. It has been reported that acacetin exhibits multiple pharmacological activities, including anti-cancer, anti-inflammation, anti-virus, anti-obesity, and anti-oxidation. These studies indicate the therapeutic potential of acacetin in liver disease. This review discussed the comprehensive information on the pathogenesis of liver disease (cirrhosis, viral hepatitis, drug-induced liver injury, and hepatocellular carcinoma), then introduced the biological source, structural features, and pharmacological properties of acacetin, and the possible application in preventing liver disease along with the pharmacokinetic and toxicity of acacetin, and future research directions. We systemically summarized the latest research progress on the potential therapeutic effect of acacetin on liver disease and existing problems. Based on the present published information, the natural flavone acacetin is an anticipated candidate agent for the treatment of liver disease.

Physiological liver microtissue 384-well microplate system for preclinical hepatotoxicity assessment of therapeutic small molecule drugs.

Hepatotoxicity can lead to the discontinuation of approved or investigational drugs. The evaluation of the potential hepatoxicity of drugs in development is challenging because current models assessing this adverse effect are not always predictive of the outcome in human beings. Cell lines are routinely used for early hepatotoxicity screening, but to improve the detection of potential hepatotoxicity, in vitro models that better reflect liver morphology and function are needed. One such promising model is human liver microtissues. These are spheroids made of primary human parenchymal and nonparenchymal liver cells, which are amenable to high throughput screening. To test the predictivity of this model, the cytotoxicity of 152 FDA (US Food & Drug Administration)-approved small molecule drugs was measured as per changes in ATP content in human liver microtissues incubated in 384-well microplates. The results were analyzed with respect to drug label information, drug-induced liver injury (DILI) concern class, and drug class. The threshold IC50ATP-to-Cmax ratio of 176 was used to discriminate between safe and hepatotoxic drugs. "vMost-DILI-concern" drugs were detected with a sensitivity of 72% and a specificity of 89%, and "vMost-DILI-concern" drugs affecting the nervous system were detected with a sensitivity of 92% and a specificity of 91%. The robustness and relevance of this evaluation were assessed using a 5-fold cross-validation. The good predictivity, together with the in vivo-like morphology of the liver microtissues and scalability to a 384-well microplate, makes this method a promising and practical in vitro alternative to 2D cell line cultures for the early hepatotoxicity screening of drug candidates.

Limitations of acetaminophen as a reference hepatotoxin for the evaluation of in vitro liver models.

Acetaminophen is commonly used as a reference hepatotoxin to demonstrate that in vitro human liver platforms can emulate features of clinical drug-induced liver injury. However, the induction of substantial cell death in these models typically requires acetaminophen concentrations (∼10 mM) far higher than blood concentrations of the drug associated with clinical hepatotoxicity (∼1 mM). Using the cytochrome P450 inhibitor 1-aminobenzotriazole, we show that acetaminophen toxicity in cultured human, mouse, and rat hepatocytes is not dependent on N-acetyl-p-benzoquinonimine formation, unlike the in vivo setting. This finding highlights the limitation of using acetaminophen as a reference hepatotoxin for the evaluation of in vitro liver models. Hence, we make recommendations on the selection of reference hepatotoxins for this purpose.

Innate immune regulation in inflammation resolution and liver regeneration in drug-induced liver injury.

Drug-induced liver injury (DILI) is an acute liver injury that poses a significant threat to human health. In severe cases, it can progress into chronic DILI or even lead to liver failure. DILI is typically caused by either intrinsic hepatotoxicity or idiosyncratic metabolic or immune responses. In addition to the direct damage drugs inflict on hepatocytes, the immune responses and liver inflammation triggered by hepatocyte death can further exacerbate DILI. Initially, we briefly discussed the differences in immune cell activation based on the type of liver cell death (hepatocytes, cholangiocytes, and LSECs). We then focused on the role of various immune cells (including macrophages, monocytes, neutrophils, dendritic cells, liver sinusoidal endothelial cells, eosinophils, natural killer cells, and natural killer T cells) in both the liver injury and liver regeneration stages of DILI. This article primarily reviews the role of innate immune regulation mediated by these immune cells in resolving inflammation and promoting liver regeneration during DILI, as well as therapeutic approaches targeting these immune cells for the treatment of DILI. Finally, we discussed the activation and function of liver progenitor cells (LPCs) during APAP-induced massive hepatic necrosis and the involvement of chronic inflammation in DILI.

Therapeutic Potential of Nutraceuticals against Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) continues to be a major concern in clinical practice, thus necessitating a need for novel therapeutic approaches to alleviate its impact on hepatic function. This review investigates the therapeutic potential of nutraceuticals against DILI, focusing on examining the underlying molecular mechanisms and cellular pathways. In preclinical and clinical studies, nutraceuticals, such as silymarin, curcumin, and N-acetylcysteine, have demonstrated remarkable efficacy in attenuating liver injury induced by diverse pharmaceutical agents. The molecular mechanisms underlying these hepatoprotective effects involve modulation of oxidative stress, inflammation, and apoptotic pathways. Furthermore, this review examines cellular routes affected by these nutritional components focusing on their influence on hepatocytes, Kupffer cells, and stellate cells. Key evidence highlights that autophagy modulation as well as unfolded protein response are essential cellular processes through which nutraceuticals exert their cytoprotective functions. In conclusion, nutraceuticals are emerging as promising therapeutic agents for mitigating DILI, by targeting different molecular pathways along with cell processes involved in it concurrently.

Turmeric supplement-associated hepatitis: a clinicopathological series of 11 cases highlighting pan-lobular and zone 3 injury.

Although turmeric is commonly ingested and well tolerated, there is increasing evidence that over-the-counter turmeric supplements can cause drug-induced liver injury. We sought to thoroughly characterise clinicopathological features of patients for whom liver injury was attributed clinically to turmeric supplements. We identified 11 patients via retrospective pathology archive review: 10 females (91%) and one male, with a median age of 58 years (range = 37-66 years). Six patients (55%) were asymptomatic with abnormal liver function tests, while five patients (45%) presented with malaise and/or jaundice. Ten patients (91%) showed predominant transaminase abnormalities, while one exhibited predominant alkaline phosphatase elevation. Histologically, biopsies showed acute hepatitis (eight cases, 73%, including five pan-lobular and three zone 3-predominant inflammation), scattered lobular aggregates of histiocytes (two; 18%) and a chronic hepatitis pattern of injury (one; 9%). Mild bile duct injury was present in five biopsies (45%). All patients stopped ingesting turmeric supplements after presenting with liver injury, and four patients additionally received steroid therapy; liver function tests normalised in all patients. Roussel Uclaf causality assessment method (RUCAM) analysis estimated the likelihood of turmeric supplement-associated liver injury to be probable (eight cases) and possible (three). Histological features in the 'possible' cases were consistent with drug-induced injury, highlighting the added benefit of histological analysis relative to RUCAM analysis isolation. This study underscores the need to obtain a full history of over-the-counter medications and supplements when investigating aetiologies for liver injury, including supplements purportedly containing innocuous compounds such as turmeric.

Topic selection for text classification using ensemble topic modeling with grouping, scoring, and modeling approach

TextNetTopics (Yousef et al. in Front Genet 13:893378, 2022. https://doi.org/10.3389/fgene.2022.893378) is a recently developed approach that performs text classification-based topics (a topic is a group of terms or words) extracted from a Latent Dirichlet Allocation topic modeling as features rather than individual words. Following this approach enables TextNetTopics to fulfill dimensionality reduction while preserving and embedding more thematic and semantic information into the text document representations. In this article, we introduced a novel approach, the Ensemble Topic Model for Topic Selection (ENTM-TS), an advancement of TextNetTopics. ENTM-TS integrates multiple topic models using the Grouping, Scoring, and Modeling approach, thereby mitigating the performance variability introduced by employing individual topic modeling methods within TextNetTopics. Additionally, we performed a thorough comparative study to evaluate TextNetTopics’ performance using eleven state-of-the-art topic modeling algorithms. We used the extracted topics for each as input to the G component in the TextNetTopics tool to select the most compelling topic model regarding their predictive behavior for text classification. We conducted our comprehensive evaluation utilizing the Drug-Induced Liver Injury textual dataset from the CAMDA community and the WOS-5736 dataset. The experimental results show that the Latent Semantic Indexing provides comparable performance measures with fewer discriminative features when compared with other topic modeling methods. Moreover, our evaluation reveals that the performance of ENTM-TS surpasses or aligns with the optimal outcomes obtained from individual topic models across the two datasets, establishing it as a robust and effective enhancement in text classification tasks.

Incidence, outcomes, and risk factors of antituberculosis drugs induced liver injury in Thailand: A retrospective cohort study

Incidence, outcomes, and risk factors of antituberculosis drugs induced liver injury in Thailand: A retrospective cohort study