Clinical characteristics and risk factors of drug-induced hepatotoxicity in cancer patients following repeated chemotherapy cycles.

BackgroundA Chinese population-based study aimed to investigate the risk factors for the incidence and severity of drug-induced liver injury (DILI) from Chinese herbal medicines and conventional Western medicines.Material/MethodsLiver biopsy and routine laboratory testing, including serum lipid measurements, was performed on 465 patients, including 168 patients with DILI and 297 patients without DILI. Histological grading of DILI used the METAVIR scoring system and the severity of DILI was graded as levels 0–5. Multivariate and univariate regression analysis were used to compare the two study groups, using a risk-adjusted odds ratio (AOR).ResultsThere was no significant association between age, alcohol status, cardiovascular disease (CVD), hypertension, or type 2 diabetes mellitus and development of DILI. However, when compared with controls, patients with dyslipidemia (AOR, 2.173; 95% CI, 1.388–3.401; P=0.001) had an increased incidence of DILI, and men had a reduced incidence of DILI when compared with women (AOR, 0.276; 95% CI, 0.169–0.450; P<0.001). Risk factors for severe DILI (≥level 3) included drinking alcohol (AOR, 6.506; 95% CI, 2.184–19.384; P=0.001), and dyslipidemia (AOR, 3.095; 95% CI, 1.345–7.123; P=0.008). Patients with an increased duration of drug treatment of >1 year had a reduced risk of developing severe DILI compared with patients with a medication duration of ≤1 month (AOR, 0.259; 95% CI, 0.084–0.802).ConclusionsIncreased risk of the incidence of DILI was significantly associated with female gender and dyslipidemia, and the risk of developing severe DILI was associated with drinking alcohol and dyslipidemia.

Drug-Induced Liver Injury: Icelandic Lessons

High prevalence, variability of clinical manifestations, limited knowledge about mechanisms of toxicity, and difficulty in diagnosis make drug-induced liver injury one of the unsolved problems in clinical medicine. Drug-induced liver injury during antiretroviral and antituberculosis therapy is a serious complication, which can reach a severe degree, leading to acute liver failure. Studies to identify the frequency, type, and severity of drug-induced liver injury in HIV-infected patients with active tuberculosis are essential. The article summarizes the current data of scientific publications on the frequency, type, and severity of drug-induced liver injury in patients treated with antiretroviral and antituberculosis drugs. A search and subsequent analysis of scientific publications in MedLine, the Cochrane Library, PubMed, and Scopus was performed. Available data indicate a high incidence of drug-induced liver injury and variation in types and severity among TB/HIV patients. This necessitates the need to examine patients taking ART and anti-TB drugs for the occurrence of liver damage, especially those with high-risk conditions such as viral hepatitis and alcohol use. It should remain a key component of TB/ HIV treatment.

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.

Biomarkers for metabolic drug activation : towards an integrated risk assessment for drug-induced liver injury (DILI)

EVALUATION OF DRUG-INDUCED LIVER INJURY BASED ON EHR AT THREE UNIVERSITY HOSPITAL IN KOREA

We used a retrospective study design to evaluated the predictive value of red cell distribution width (RDW) for drug-induced liver injury (DILI) severity in Chinese patients with liver biopsy to assist with early DILI management. We included 164 DILI patients with complete laboratory information and medical history. We compared outcomes of 36 patients with severe DILI with outcomes of a control group of 128 patients with mild-to-moderate DILI. Multivariate analyses of risk factors for severe liver injury in Chinese patients with DILI revealed an estimated adjusted odds ratio (AOR) (95% CI) of 4.938 (1.088–22.412) in patients with drinking. Risk for serious liver injury was also increased significantly in patients with dyslipidemia [AOR (95% CI) 3.926 (1.282–12.026)], higher serum total bile acid (TBA) levels [AOR (95% CI) 1.014 (1.009–1.020)] and higher RDW [AOR (95% CI) 1.582 (1.261–1.986)]. The result for area under the curve of 0.905 for TBA levels indicated this variable had high diagnostic performance for predicting DILI severity. Based on an area under the curve value of 0.855, RDW also had superior diagnostic performance in prediction of DILI severity. This performance was not significantly different compared with TBA and was superior compared with other variables, which had area under values ranging from poor to failure (0.527–0.714).The risk for severe DILI was associated with drinking, dyslipidemia, higher TBA levels and RDW values. This study found that RDW and TBA levels were predictors of DILI severity in Chinese patients.

Direct-Acting Antivirals for Chronic Hepatitis C: Can Drug Properties Signal Potential for Liver Injury?

Background Drug-induced liver injury (DILI) is a complex liver pathology modulated by multiple factors, most of which remain unknown. Previous studies have suggested that concomitant medications and patient characteristics play an important role as modulators of this disease. This study aimed to determine the most relevant concomitant medications and patient characteristics that influence the severity of idiosyncratic DILI. Methods Two clinical databases, discovery and validation, were analyzed to evaluate host and drug properties. Predictive algorithms, elastic net regression model and logistic regression model, were implemented using R, both achieving ROC AUC > 0.7. Results The findings revealed the existence of significant relationship between DILI severity and multiple factors. These factors included: hepatocellular injury, hydrophobic drugs with logP > 3 (octanol-water partition coefficient), and the use of concomitant medications containing halogen compounds or heterorings when taken together with culprit drugs with significant hepatic metabolism. Conclusions These findings offer valuable insights into predicting the severity of DILI. By identifying the key factors that influence the severity of DILI, it would be possible for healthcare providers to predict the severity of damage in a patient with DILI. This enables early interventions in cases of DILI, thus subsequently reducing its negative effects.

Background: Drug-induced liver injury (DILI) can be prevented if diagnosed and treated timeously. The identification and primary prevention of DILI risk factors presents the rational means of reducing hospital costs and mortality.Methods: A retrospective chart review was conducted of clinical in-patient records of all adult patients admitted to Northdale Hospital (NDH) with a diagnosis of DILI. Patients with pre-existing liver disease were excluded.Results: A total of 95 patient files with DILI were reviewed. The burden of DILI at NDH over the two-year period was 0.19%. The average age was 38 years, with a slightly higher female preponderance (62.1%). A lower serum albumin level (mean 21.35 g/dl) was significantly associated with DILI (p 0.001). Forty-six patients had a history of alcohol consumption, which increased the risk of DILI (OR 2.1). Of the patients reviewed, 62 (65%) were on antiretroviral therapy (ART) whereas 41 (43%) were on tuberculosis treatment (TBT) at presentation. The most common co-morbidities associated with DILI were HIV (75.7%), TB (43.2%), renal disease (34.7%) and malnutrition (31.6%). The most common hepatotoxins, apart from ART and TBT, were paracetamol (46.3%), cotrimoxazole (32.6%), alcohol (48.4%) and traditional medication (27.4%).Conclusion: This study demonstrated associations with the development of DILI and being female gender, younger age group, hypoalbuminaemia and renal failure. The use of alcohol, traditional medication and the overzealous use and prescription of paracetamol to patients who present with DILI is concerning. The case fatality rate of 14.7% demonstrates the importance of identifying these potential risk factors timeously.

Introduction: To analyze the clinical characteristics and influencing factors of drug-induced liver injury (DILI) in pediatric patients with newly diagnosed Acute Lymphoblastic Leukemia (ALL) during chemotherapy, using a retrospective analysis. Methods: A retrospective analysis was conducted on 189 pediatric ALL patients treated at our institution from January 2019 to March 2024. The incidence and related factors of DILI were assessed, including body mass index (BMI), vitamin D levels, absolute neutrophil counts, and the number of blood transfusions. Results: The study found that the incidence of DILI was 21.34%. Statistical analysis indicated that BMI, vitamin D levels, absolute neutrophil counts, and the number of transfusions were independent factors influencing the occurrence of DILI during chemotherapy in children with ALL (P&lt;0.05). Moreover, DILI presented in various forms, predominantly as hepatocellular injury, mixed type, and cholestatic type, with hepatocellular injury being the most common. Conclusion: Body mass index, vitamin D levels, absolute neutrophil counts, and the number of transfusions are critical independent factors affecting the development of drug-induced liver injury in pediatric patients with acute leukemia during chemotherapy. In clinical practice, proactive intervention on these factors is essential. Prompt actions such as discontinuing or adjusting medication dosages, hepatic protection, enzyme reduction, and jaundice management are vital to ensure the recovery of all patients.

A High Serum Level of Taurocholic Acid Is Correlated With the Severity and Resolution of Drug-induced Liver Injury

Acute Liver Failure: Indian Perspective.

Genetic polymorphisms in cytotoxic T lymphocyte-associated antigen 4 (CTLA4) play an influential role in graft rejection and the long-term clinical outcome of organ transplantation. We investigated the association of 5 CTLA4 single-nucleotide polymorphisms (SNPs) (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A) with drug-induced liver injury (DILI) in Chinese renal transplantation (RT) recipients. Each recipient underwent a 24-month follow-up observation for drug-induced liver damage. The CTLA4 SNPs were genotyped in 864 renal transplantation recipients. A significant association was found between the rs231775 genotype and an early onset of DILI in the recipients. Multivariate analyses revealed that a risk factor, recipient rs231775 genotype (p = 0.040), was associated with DILI. Five haplotypes were estimated for 4 SNPs (excluding rs733618); the frequency of haplotype ACGG was significantly higher in the DILI group (68.9%) than in the non-DILI group (61.1%) (p = 0.041). In conclusion, CTLA4 haplotype ACGG was partially associated with the development of DILI in Chinese kidney transplant recipients. The rs231775 GG genotype may be a risk factor for immunosuppressive drug-induced liver damage.

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