Risk Factors For Drug-induced Liver Injury Research Articles

Retrospective evaluation of medical information for predicting tazobactam/piperacillin-induced liver injury.

Tazobactam/piperacillin is a first-line treatment option for hospital-acquired pneumonia; however, drug-induced liver injury (DILI) is relatively frequently observed with tazobactam/piperacillin in clinical practice. This study aimed to verify the usefulness of available patient data for predicting DILI prior to tazobactam/piperacillin administration. Tazobactam/piperacillin-treated patients were retrospectively selected and divided into patients with and without DILI. Comparative analysis was performed regarding age, gender, dose, duration of treatment, clinical laboratory values prior to treatment initiation, and the types of organ-specific infections in both groups. Multiple logistic regression analyses indicated that elevated C-reactive protein (odds ratio (OR), 1.284; 95% confidence interval (CI), 1.172 - 1.406; p < 0.001) and high hemoglobin (OR, 1.697; 95% CI, 1.259 - 2.286; p < 0.001) levels prior to the administration of tazobactam/piperacillin were risk factors for DILI in males who received a 4.5-g dose. A predictive model for DILI risk was constructed by combining these test values and analyzed using receiver operating characteristic curves, obtaining 0.910 for the model construction set and 0.845 for the validation set. The development of DILI was predicted with good accuracy in males who received a 4.5-g dose with elevated C-reactive protein and hemoglobin.

N-acetyltransferase Gene Variants Involved in Pediatric Idiosyncratic Drug-Induced Liver Injury.

Idiosyncratic drug-induced liver injury (DILI) is a complex multifactorial disease in which the toxic potential of the drug, together with genetic and acquired factors and deficiencies in adaptive processes, which limit the extent of damage, may determine susceptibility and make individuals unique in their development of hepatotoxicity. In our study, we sequenced the exomes of 43 pediatric patients diagnosed with DILI to identify important gene variations associated with this pathology. The result showed the presence of two variations in the NAT2 gene: c.590G>A (p.Arg197Gln) and c.341T>C (p.Ile114Thr). These variations could be found separately or together in 41 of the 43 patients studied. The presence of these variations as a risk factor for DILI could confirm the importance of the acetylation pathway in drug metabolism.

Clinical Features and Risk Factors for Drug-Induced Liver Injury: A Retrospective Study From China

PurposeWith the prolongation of human life expectancy and the outbreak of COVID-19, antineoplastic agents, anti-infective drugs, and cardiovascular system drugs have been widely applied, resulting in a growing incidence of drug-induced liver injury (DILI) year by year. This study aimed to investigate signals, clinical characteristics, and risk factors in patients with liver injury. MethodsA retrospective analysis was conducted on inpatients clinically diagnosed with DILI from 2019 to 2021 in one tertiary hospital in mainland China. The hepatic biochemical indices, clinical manifestations and suspected drugs of the patients were counted. We determined causality assessed by the Roussel Uclaf Causality Assessment Method in patients that the biochemistry met the diagnostic criteria recommended by the International Serious Adverse Events Consortium and compared them with contemporaneous patients diagnosed as DILI but with hepatic biochemical abnormalities only to identify the injure types and risk factors for DILI. FindingsA total of 1167 patients from 2639 initial participants with DILI were included. According to the injured target cells, it can be divided into hepatocellular injury type 351 cases (30.08%), cholestatic injury type 97 cases (8.31%), mixed injury type 27 cases (2.31%), and biochemical abnormal only type 692 cases (59.30%). It involved 1738 cases of suspected drugs, 349 drugs, and the top 3 drug categories were antineoplastic agents, anti-infectives, and traditional Chinese medicines, with Cyclophosphamide, Atorvastatin, and Liuzasulfapyridine as the top 3 in order of ranking. The main symptoms of patients were darker urine, decreased appetite, and yellow sclera. The overall prognosis of patients with DILI was favorable, with 280 recovered cases (23.99%), 691 improved cases (59.21%), 189 not improved cases (16.20%), and 7 deaths (0.60%). There were significant differences in gender, age, malignancy, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, gamma-glutamyltransferase, albumin, international normalized ratio, and prognosis among patients with different injury types (P < 0.05). Multiple logistic regression analysis showed that female (odds ratio [OR] = 1.897, P < 0.001), alcohol use (OR = 1.905, P = 0.001), malignancy (OR = 0.417, P < 0.001), and pregnancy (OR = 0.201, P = 0.011) were independent factors influencing DILI. ImplicationsFor most patients with liver injury, the manifestations are mild elevation of liver biochemistry without other symptoms (biochemical abnormal only type). The rest of the patients are predominantly of the hepatocellular injury type. Female and alcohol abuse patients are the risk factors of DILI, reminding clinicians to strengthen education on safe drug use, give individualized treatment, and regularly monitor liver function indexes in the patients.

An analysis on clinical characteristics and prognosis-related risk factors in patients with drug-induced liver injury

Objective: To explore the drugs and clinical characteristics causing drug-induced liver injury (DILI) in recent years, as well as identify drug-induced liver failure, and chronic DILI risk factors, in order to better manage them timely. Methods: A retrospective investigation and analysis was conducted on 224 cases diagnosed with DILI and followed up for at least six months between January 2018 and December 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors for drug-induced liver failure and chronic DILI. Results: Traditional Chinese medicine (accounting for 62.5%), herbal medicine (accounting for 84.3% of traditional Chinese medicine), and some Chinese patent medicines were the main causes of DILI found in this study. Severe and chronic DILI was associated with cholestatic type. Preexisting gallbladder disease, initial total bilirubin, initial prothrombin time, and initial antinuclear antibody titer were independent risk factors for DILI. Prolonged time interval between alkaline phosphatase (ALP) and alanine aminotransferase (ALT) falling from the peak to half of the peak (T(0.5ALP) and T(0.5ALT)) was an independent risk factor for chronic DILI [area under the receiver operating characteristic curve (AUC) = 0.787, 95%CI: 0.697~0.878, P < 0.001], with cutoff values of 12.5d and 9.5d, respectively. Conclusion: Traditional Chinese medicine is the main contributing cause of DILI. The occurrence risk of severe DILI is related to preexisting gallbladder disease, initial total bilirubin, prothrombin time, and antinuclear antibodies. T(0.5ALP) and T(0.5ALT) can be used as indicators to predict chronic DILI.

DRUG INDUCED LIVER INJURY: A SYSTEMATIC REVIEW

Drug-induced liver injury (DILI), which has a variety of pathophysiological characteristics, is an important clinical problem. This review offers a thorough analysis of DILI, covering its pathophysiological mechanisms, the interaction between the microbiota and liver disease, the potential benefit of probiotics in preventing or treating DILI, diagnostic and prognostic methods, risk factors for DILI, current prevalence rates, and available treatments. The emergence of liver damage is influenced by the complex interplay of drug metabolism, immunological responses, and hereditary variables. An extensive list of medications, nutritional supplements, herbal products, and chemotherapeutic medicines that have been linked to DILI is provided based on the various research papers. The impact of the gut microbiota on healthy liver function and liver disease has been clarified by recent studies. Drug metabolism, immunological responses, and hepatic inflammation can all be affected by changes in gut microbial makeup and function, thereby worsening DILI. Probiotics’ impact on the gut-liver axis and their potential therapeutic advantages in the prevention and treatment of DILI are investigated. For effective management of DILI, a precise diagnosis and prognosis are essential. The outcomes of patients are predicted and treatment choices are guided by prognostic variables, such as liver function tests and drug causality evaluation tools. Inherited liver illnesses, genetic differences, patient characteristics, concurrent medication use, and other risk factors all have a role in the development of DILI. Identification of those at higher risk and the facilitation of specialized preventative interventions and patient monitoring is made possible by the recognition of these risk factors. DILI prevalence rates differ between populations and geographical areas. Planning for public health and allocating resources depend on tracking the incidence and prevalence of DILI. Although supportive care and medication withdrawal are the mainstays of DILI treatment, severe cases may call for a liver transplant. As a result, DILI is a multifactorial disorder that necessitates a thorough understanding of its processes, risk factors, diagnosis, and therapy. New insights into the gut microbiota and the possible impact of probiotics present intriguing directions for further study and treatment approaches to reduce liver damage caused by DILI.

Risk factors for amiodarone-induced liver injury: A retrospective analysis of medical records.

This study identified risk factors for drug-induced liver injury (DILI) based on patient information before the administration of amiodarone. A retrospective analysis was performed on patients who had received amiodarone treatment. Data from patients with and without DILI were compared immediately before the start of amiodarone treatment. An elevated C-reactive protein level (odds ratio (OR) 1.119; 95% confidence interval (CI) 1.009 - 1.241; p = 0.033) before amiodarone administration was a significant risk factor for DILI. Possible treatment with alternative drugs should be considered in patients with elevated C-reactive protein levels. Moreover, close monitoring of liver function when amiodarone is administered may prevent the onset and exacerbation of DILI.

Metabolic Disorders Are Associated With Drug-Induced Liver Injury During Antituberculosis Treatment: A Multicenter Prospective Observational Cohort Study in Korea.

Drug-induced liver injury (DILI) may lead to the discontinuation of antituberculosis (anti-TB) treatment (ATT). Some studies have suggested that metabolic disorders increase the risk of DILI during ATT. This study aimed to identify risk factors for DILI, particularly metabolic disorders, during ATT. A multicenter prospective observational cohort study to evaluate adverse events during ATT was conducted in Korea from 2019 to 2021. Drug-susceptible patients with TB who had been treated with standard ATT for 6 months were included. The patients were divided into 2 groups depending on the presence of 1 or more metabolic conditions, such as insulin resistance, hypertension, obesity, and dyslipidemia. We monitored ATT-related adverse events, including DILI, and treatment outcomes. The incidence of DILI was compared between individuals with and without metabolic disorders, and related factors were evaluated. Of 684 patients, 52 (7.6%) experienced DILI, and 92.9% of them had metabolic disorders. In the multivariable analyses, underlying metabolic disorders (adjusted hazard ratio [aHR], 2.85; 95% CI, 1.01-8.07) and serum albumin <3.5 g/dL (aHR, 2.26; 95% CI, 1.29-3.96) were risk factors for DILI during ATT. In the 1-month landmark analyses, metabolic disorders were linked to an elevated risk of DILI, especially significant alanine aminotransferase elevation. The treatment outcome was not affected by the presence of metabolic disorders. Patients with metabolic disorders have an increased risk of ATT-induced liver injury compared with controls. The presence of metabolic disorders and hypoalbuminemia adversely affects the liver in patients with ATT.

Does diabetes mellitus comorbidity increase the risk of drug-induced liver injury during tuberculosis treatment?

The growing burden of diabetes worldwide is a threat to tuberculosis (TB) control. Drug-induced liver injury (DILI) due to TB drugs is a significant concern and there is currently limited evidence on the effect of diabetes on TB DILI. This study sought to investigate the effect of diabetes as a risk factor for DILI and to further study any potential co-factors. An unmatched case-control study. Cases were TB patients on 2RHZE/4RH presenting with DILI from 2013-2017 in Porto Alegre, Brazil. Controls were contemporaneous TB patients without DILI being treated in any one of the same five Porto Alegre TB clinics. The exposure variables were diabetes (main exposure variable), age, sex, alcohol misuse, human immunodeficiency virus (HIV), hepatitis C (HCV) and B (HBV) viruses, concomitant hepatotoxic drugs, other liver diseases and TB site. The outcome variable was the occurrence of DILI. Odds of DILI were increased by: older age group 51-60, 61-70 and 71-93 years (adjusted OR 2.39, 95%CI 1.30-4,38; adjusted OR 4.37, 2.28-8,35; adjusted OR 12.91, 5.81-28,66, respectively), HIV positive status (adjusted OR 3.59, 95%CI 2.25-5.73), HCV positive status (adjusted OR 3.49, 95%CI 1.96-6.21) and having concurrent pulmonary and extrapulmonary TB (adjusted OR 3.16, 95%CI 1.93-5.19). Diabetes, gender, and other hepatotoxic drugs were not associated with DILI. This study confirms the association between TB DILI and well-known risk factors but did not demonstrate increased odds of TB DILI in patients with diabetes.

Retrospective analysis of risk factors for levofloxacin-induced liver injury

Levofloxacin is used as a first-line drug for the treatment of Legionella pneumonia. However, the relatively high incidence of drug-induced liver injury (DILI) remains a clinical problem. Based on the available patient data, this study aimed to identify the risk factors for DILI before levofloxacin administration. Multiple logistic regression analyses suggested that male sex (odds ratio [OR], 6.975; 95% confidence interval [CI], 1.737–28.000; p = 0.006), elevated C-reactive protein level (OR, 1.182; 95% CI, 1.089–1.283; p = 0.0006), and high haemoglobin level (OR, 1.640; 95% CI, 1.226–2.195; p = 0.001) before administration of levofloxacin were risk factors for DILI. Possible treatment with alternative drugs should be considered in male patients with elevated C-reactive protein and haemoglobin levels. Moreover, close monitoring of liver function tests when levofloxacin is administered may prevent the development and severity of DILI.

Genetics of drug-induced liver injury: Current knowledge and future prospects.

Idiosyncratic drug-induced liver injury (DILI) remains an important clinical problem, both during drug development and the prescription of a range of licensed drugs. Although rare, the consequences are serious. Ongoing studies on genetic risk factors for DILI, especially genomewide association studies, have resulted in the identification of a number of genetic risk factors, including particular HLA alleles and a few non-HLA genes, both immune-related and metabolic. Some non-HLA associations, such as N-acetyltransferase 2 in isoniazid DILI and interferon regulatory factor 6 in interferon-beta DILI are likely to be drug-specific due to the role of the associated gene, but there is also evidence for polygenic susceptibility involving pathways such as oxidative and endoplasmic reticulum stress and mitochondrial function for DILI induced by multiple drugs. Increased knowledge of genetic risk factors should assist in better understanding underlying DILI mechanisms and help improve methods for identifying hepatotoxic drugs early in development. HLA allele-specific T cell proliferation together with in silico prediction of drug binding to specific HLA proteins have confirmed genetic findings for certain common causes of DILI. However, studies in hepatocytes exposed to high drug concentrations suggest toxicity that is not dependent on genotype also occurs. It seems likely that susceptibility to DILI involves several genetic risk factors combining with other factors that affect drug levels. Despite recent progress in detecting genetic risk factors for DILI, low positive predictive values mean that general implementation of genotyping prior to prescription of potentially hepatotoxic drugs is not useful currently.

S1208 Prevalence of Hepatitis B Virus (HBV) and Latent Tuberculosis Co-Infection and Risk of Drug-Induced Liver Injury Across Two Large HBV Cohorts in the United States

Introduction: Screening for hepatitis B virus (HBV) infection prior to starting tuberculosis (TB) treatment is important because HBV-TB co-infected patients have increased risk of drug-induced liver injury (DILI). However, there are limited real-world data on epidemiology of HBV-latent TB infection (LTBI) in the US. We evaluated prevalence and predictors of HBV-LTBI co-infection and DILI risk among two distinct US chronic HBV cohorts. Methods: Adults with chronic HBV from 2010–2020 were identified among the Chronic Hepatitis Cohort Study (CHeCS) and the Veterans Affairs national chronic HBV cohort (VA-HBV). HBV-LTBI co-infection was identified based on laboratory data (TB-Quantiferon), ICD-9/10 codes, and prescription data. DILI was identified based on established definitions that incorporated ICD-9/10 codes and changes in alanine aminotransferase levels following start of LTBI treatment. Results: Among 6,019 chronic HBV patients in the CHeCS cohort (44% female; 47% age 18-39y, 39% age 40-59y, 14% age >60y; 47% Asian, 20% non-Hispanic white (NHW), 14% African American (AA), 1% Hispanic; 3% HCV; 6% HIV), 9.1% were tested for TB, among which 7.7% had HBV-LTBI. Significantly higher odds of HBV-LTBI were observed in women vs. men (13% vs. 5%, OR 2.57, 95% CI 1.36-4.85 p< 0.01), but no other significant differences were observed. Among HBV-LTBI patients that received LTBI treatment, 28.6% developed DILI. Among 12,928 predominantly U.S.-born chronic HBV patients in the VA-HBV cohort (94% male; 6% age 18-39y, 30% age 40-59y, 65% age >60y; 10% Asian, 42% AA, 39% NHW, 2% Hispanic; 86% US-born; 15% HCV; 2.3% HIV), 14.7% were tested for TB, among which 14.5% had HBV-LTBI. Significantly higher odds of HBV-LTBI were observed in AA vs. NHW (15% vs. 12%, OR 1.70, 95% CI 1.18-2.43, p< 0.01) and in non-US born vs. US-born (25% vs. 13%, OR 2.13, 95% CI 1.34-4.00, p< 0.05). Among HBV-LTBI patients that received LTBI treatment, the proportion of patients that developed DILI was 3.6%. Conclusion: Among two large distinct US cohorts of chronic HBV patients, testing for LTBI was infrequent despite relatively high prevalence of HBV-LTBI. While nearly 30% of HBV-LTBI patients in the predominantly Asian and younger CHeCS cohort developed DILI, only 3.6% in the predominantly older, US born VA-HBV cohort developed DILI. Better understanding risk factors for DILI among HBV-LTBI patients can help guide clinicians to appropriately modify LTBI treatment to reduce DILI risk. Supported by ACG Clinical Research Award (Figure).Figure 1.: Prevalence of HBV-LTBI Co-Infection and Risk of DILI.

Drug-Induced Liver Injury: A Literature Review

Drug-Induced liver injury (DILI) is a common harmful drug reaction of some medication which can cause the damage to liver cells, or might be a chance of death. In the western countries DILI is the main cause for acute liver failure. These reactions are very common because almost all drug regimens can cause injury to liver. Most of DILI cases are harmless and they get better after stopping the offending drug. These reactions are mainly due to some pharmacological remedies, traditional medications, herbal and nutritional supplements. Due to these harmful reactions, elevation is noticed in the liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphate, total bilirubin) 2N from its normal value. Drug-induced liver injury includes 1,000 of pharmacological remedies or more. Here, we review the maximum current literature, so the treatment includes timely diagnosis and removal of the doubtable medication is the key. This paper explains the different causes, pharmacological medications responsible for drug-induced liver injury, effect of covid-19 on liver injury and future perspective. It is important to be aware of and remove the suspected agent as soon as possible. There are no specific risk factors for DILI, but existing liver disease and genetic factors may be a priority for some people. Treatment of liver damage caused by drugs and herbs includes immediate drug withdrawal and supportive care aimed at alleviating unwanted symptoms. Main purpose of this paper is to deliver the info about the DILI, which are dose related, identification and consideration of disease.&#x0D; Keywords: Drug-Induced liver injury (DILI), Pathophysiology, Diagnosis, Treatment, Risk factors and effect of covid-19 on liver injury.

Minimal Risk of Drug-Induced Liver Injury With Molnupiravir and Ritonavir-Boosted Nirmatrelvir

Minimal Risk of Drug-Induced Liver Injury With Molnupiravir and Ritonavir-Boosted Nirmatrelvir

Study on the Characteristics of Small-Molecule Kinase Inhibitors-Related Drug-Induced Liver Injury.

Background and Aim: More than half of the small-molecule kinase inhibitors (KIs) induced liver injury clinically. Meanwhile, studies have shown a close relationship between mitochondrial damage and drug-induced liver injury (DILI). We aimed to study KIs and the binding between drugs and mitochondrial proteins to find factors related to DILI occurrence. Methods: A total of 1,223 oral FDA-approved drugs were collected and analyzed, including 44 KIs. Fisher’s exact test was used to analyze DILI potential and risk of different factors. A total of 187 human mitochondrial proteins were further collected, and high-throughput molecular docking was performed between human mitochondrial proteins and drugs in the data set. The molecular dynamics simulation was used to optimize and evaluate the dynamic binding behavior of the selected mitochondrial protein/KI complexes. Results: The possibility of KIs to produce DILI is much higher than that of other types (OR = 46.89, p = 9.28E-13). A few DILI risk factors were identified, including molecular weight (MW) between 400 and 600, the defined daily dose (DDD) ≥ 100 mg/day, the octanol–water partition coefficient (LogP) ≥ 3, and the degree of liver metabolism (LM) more than 50%. Drugs that met this combination of rules were found to have a higher DILI risk than controls (OR = 8.28, p = 4.82E-05) and were more likely to cause severe DILI (OR = 8.26, p = 5.06E-04). The docking results showed that KIs had a significant higher affinity with human mitochondrial proteins (p = 4.19E-11) than other drug types. Furthermore, the five proteins with the lowest docking score were selected for molecular dynamics simulation, and the smallest fluctuation of the backbone RMSD curve was found in the protein 5FS8/KI complexes, which indicated the best stability of the protein 5FS8 bound to KIs. Conclusions: KIs were found to have the highest odds ratio of causing DILI. MW was significantly related to the production of DILI, and the average docking scores of KI drugs were found to be significantly different from other classes. Further analysis identified the top binding mitochondrial proteins for KIs, and specific binding sites were analyzed. The optimization of molecular docking results by molecular dynamics simulation may contribute to further studying the mechanism of DILI.

Roles of Cofactors in Drug-Induced Liver Injury: Drug Metabolism and Beyond.

Drug-induced liver injury (DILI) remains one of the major concerns for healthcare providers and patients. Unfortunately, it is difficult to predict and prevent DILI in the clinic because detailed mechanisms of DILI are largely unknown. Many risk factors have been identified for both "intrinsic" and "idiosyncratic" DILI, suggesting that cofactors are an important aspect in understanding DILI. This review outlines the cofactors that potentiate DILI and categorizes them into two types: (1) the specific cofactors that target metabolic enzymes, transporters, antioxidation defense, immune response, and liver regeneration; and (2) the general cofactors that include inflammation, age, gender, comorbidity, gut microbiota, and lifestyle. The underlying mechanisms by which cofactors potentiate DILI are also discussed. SIGNIFICANCE STATEMENT: This review summarizes the risk factors for DILI, which can be used to predict and prevent DILI in the clinic. This work also highlights the gaps in the DILI field and provides future perspectives on the roles of cofactors in DILI.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

A Multiple Logistic Regression Model Based on Gamma-Glutamyl Transferase as a Biomarker for Early Prediction of Drug-Induced Liver Injury in Vietnamese Patients.

The discovery of new biomarkers and the causality of drug-induced liver injury (DILI) is a major focus in modern medicine. Alcoholism is considered a risk factor for DILI. However, the extraction and assessment of alcohol history are difficult due to noncooperation by patients and intermittent management. Therefore, we conducted a case-control study of 1277 patients diagnosed with DILI according to the Roussel Uclaf Causality Assessment Method scale to evaluate gamma-glutamyl transferase (GGT) as a biomarker for predicting DILI in Vietnamese patients, where the proportion of alcoholism is quite high. Further, we built and validated a logistic regression model to predict the risk of DILI in hospitalized patients. The risk of DILI increased by 10% for 1 UI/L higher levels of GGT before prescription (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.01). A history of alcoholism was not a risk factor for DILI occurrence (OR, 1.83; 95%CI, 0.99-3.04; P = .057). A logistic regression model was successfully built and validated based on age; sex; initial levels of alanine aminotransferase, alkaline phosphatate, GGT, likelihood score of the suspected drug, and history of liver disease; the area under the receiver operating characteristic curve of the model was 0.883 (95%CI, 0.868-0.897). Our results thus suggest the necessity of exercising caution when prescribing to patients without a history of alcoholism but having high GGT levels. This model can be applied clinically to assess the risk of DILI before prescribing to reduce the risk of DILI in the patient.

The Characteristics, Prevalence, and Risk Factors of Drug-Induced Liver Injury Among Brucellosis Inpatients in Xinjiang, China.

Background: We investigated the prevalence, demographic and clinical features, and risk factors associated with drug-induced liver injury (DILI) during the treatment of brucellosis inpatients in a retrospective study. Methods: We collected the clinical data of 782 brucellosis inpatients admitted at the Shawan County People’s Hospital, Xinjiang, from 2015–2019. All cases were re-evaluated using the international consensus of DILI criteria and RUCAM rating scale. 71 patients were confirmed as DILI cases and compared with 523 other patients with normal liver function. Results: It was indicated that DILI occurred with a prevalence of about 9.08% among brucellosis inpatients receiving drug therapy. Hepatocellular injury was the most common type of DILI (61.97%, 95% confidence interval [CI] 50.34–72.37), followed by mixed (23.94%, 95% CI 15.52–35.04) and cholestatic types (14.08%, 95% CI 7.83–24.02). In addition, 13.64% of the hepatocellular DILI cases fulfilled Hy’s law criteria and only two cases (2.82%) progressed to severe DILI. Most patients adopted the combination of rifampicin, antipyretic analgesics, anti-infective agents, and traditional Chinese medicine for the treatment of brucellosis, with all the 71 patients taking rifampicin as the drug of choice. Multivariable logistic regression analyses indicated that obesity, regular alcohol intake, and decreased serum albumin were the independent risk factors of DILI in patients with brucellosis after adjusting for gender, age, and ethnicity. Conclusion: DILI occurred in a minority of inpatients diagnosed with brucellosis receiving rifampicin-based therapeutic regimen. In addition, obesity, alcohol abuse, and decreased serum albumin were valuable predictors of the risk of DILI in patients with brucellosis.

Incidence and risk factors of anti-tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients.

Anti-tuberculosis drugs remain as an important cause of drug-induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti-tuberculosis DILI (ATDILI). Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis. In the derivation cohort (n=3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR=1.014, 95% CI: 1.005-1.023), baseline ALT (HR=1.014, 95% CI: 1.003-1.024), haemoglobin (HR=1.011, 95% CI: 1.002-1.020) and HBsAg positivity (HR=1.516, 95% CI: 1.004-2.290) were independent risk factors for DILI. In the second cohort (n=1497) of which 85 (5.7%) developed ATDILI. Age (HR=1.029, 95% CI: 1.003-1.056), baseline AST (HR=1.036, 95% CI: 1.010-1.062), previous TB treatment (HR=3.894, 95% CI: 1.304-11.625) and active drinking (HR=3.624, 95% CI: 1.147-11.454) were risk factors for developing jaundice. Elevation of ALT of ≥3×ULN during anti-TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients.

Antidepressants- and antipsychotics-induced hepatotoxicity.

Drug-induced liver injury (DILI) is a serious health burden. It has diverse clinical presentations that can escalate to acute liver failure. The worldwide increase in the use of psychotropic drugs, their long-term use on a daily basis, common comorbidities of psychiatric and metabolic disorders, and polypharmacy in psychiatric patients increase the incidence of psychotropics-induced DILI. During the last 2 decades, hepatotoxicity of various antidepressants (ADs) and antipsychotics (APs) received much attention. Comprehensive review and discussion of accumulated literature data concerning this issue are performed in this study, as hepatotoxic effects of most commonly prescribed ADs and APs are classified, described, and discussed. The review focuses on ADs and APs characterized by the risk of causing liver damage and highlights the ones found to cause life-threatening or severe DILI cases. In parallel, an overview of hepatic oxidative stress, inflammation, and steatosis underlying DILI is provided, followed by extensive review and discussion of the pathophysiology of AD- and AP-induced DILI revealed in case reports, and animal and in vitro studies. The consequences of some ADs and APs ability to affect drug-metabolizing enzymes and therefore provoke drug–drug interactions are also addressed. Continuous collecting of data on drugs, mechanisms, and risk factors for DILI, as well as critical data reviewing, is crucial for easier DILI diagnosis and more efficient risk assessment of AD- and AP-induced DILI. Higher awareness of ADs and APs hepatotoxicity is the prerequisite for their safe use and optimal dosing.