Genome-wide methylation analysis in Anti-tuberculosis Drug Induced Liver Injury case and control samples
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE124415 | GEO | 2021/12/24
REPOSITORIES: GEO
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Project description:The antimicrobials isoniazid and pyrazinamide, used for the treatment of tuberculosis are known to cause drug-induced liver injury in humans. This limits the effectiveness of tuberculosis treatment, resulting in incomplete cure, relapse and the development of antimicrobial resistance. MicroRNAs are known to be good biomarkers of disease, with the microRNA miR-122 being diagnostic for liver injury. In this study zebrafish larvae were exposed to the anti-tuberculosis drugs isoniazid and pyrazinamide at concentrations which demonstrated liver injury by microscopy and histology. The aim of this study is to understand small RNA changes occurring in anti-tuberculosis drug-induced liver injury and to attempt to identify novel microRNA biomarkers of liver injury.
2023-12-25 | GSE146260 | GEO
Project description:Genome-wide methylation analysis in Anti-tuberculosis Drug Induced Liver Injury case and control samples
| PRJNA511986 | ENA
Project description:WTCCC genome-wide case-control association study for Tuberculosis (TB) using the African samples as controls.
| EGAS00000000027 | EGA
Project description:The pathogenesis of liver damage induced by anti-tuberculosis drugs is not fully understood, andcurrently, there is no clinically useful biomarker for early diagnosis and treatment.By comparing the differences in the expression of global gene transcripts in the serum of patients with and without anti-tuberculosis drugs induced liver injury, dysregulation genes not only provides a basis for studying pathogenesis, but also provides important information to find new targets for diagnosis and treatment of disease. We used microarrays to detail the global programme of gene expression in sera underlying anti-tuberculosis drug-induced liver injury and identified distinct classes of transcript during this process.
2021-01-01 | GSE141362 | GEO
Project description:Small RNAs in anti-tuberculosis drug-induced liver injury
| PRJNA609915 | ENA
Project description:Purpose of this reviewIn order to combat the development of drug resistance, the clinical treatment of tuberculosis requires the combined use of several anti-tuberculosis (anti-TB) drugs, including isoniazid and rifampicin. Combinational treatment approaches are suggested by the World Health Organization (WHO) and are widely accepted throughout the world. Unfortunately, a major side effect of the treatment is the development of anti-tuberculosis drug-induced liver injury (AT-DILI). Many factors contribute to isoniazid- and rifampicin-mediated AT-DILI and genetic variations are among the most common factors. The purpose of this review is to provide information on genetic variations associated with isoniazid- and rifampicin-mediated AT-DILI.Recent findingsThe genetic variations associated with AT-DILI have been identified in the genomic regions within or near genes encoding proteins in the following pathways: drug metabolizing enzymes (NAT2, CYP2E1, and GSTs), accumulation of bile acids, lipids, and heme metabolites (CYP7A1, BSEP, UGTs, and PXR), immune adaptation (HLAs and TNF-α), and oxidant challenge (TXNRD1, SOD1, BACH1, and MAFK).SummaryThe information summarized in this review considers the genetic bases of risk factors contributing to AT-DILI and provides information that may help for future studies. Some of the implicated genetic variations can be used in the design of genetic tests and serve as biomarkers for the prediction of isoniazid- and rifampicin-mediated AT-DILI risk in personalized medicine.
| S-EPMC6241288 | biostudies-literature
Project description:BackgroundPulmonary tuberculosis patients infected with hepatitis B are at high risk for drug-induced liver injury.Case presentationA 42-year-old Indonesian female complained of sclera icterus, tea-colored urine, vomiting, dyspnea, and swollen stomach and legs. The patient experienced this condition after taking anti-tuberculosis drugs for five days. Her medical history showed hepatitis B and cirrhosis. Follow-up examination included chest X-ray and GeneXpert supported a diagnosis of pulmonary tuberculosis. However, abdominal ultrasonography indicated ascites and cirrhosis. We diagnosed the patient with anti-tuberculosis DILI, cirrhosis Child-Pugh C (score 12) related to hepatitis B, and pulmonary tuberculosis. We decided to stop the anti-tuberculosis drug. We treated the patient using tenofovir, hepatoprotective drug, diuretics, and albumin infusion. On the third day, the patient received new anti-tuberculosis drugs, including levofloxacin 750 mg, ethambutol 1000 mg, and streptomycin 1000 mg (LES). The patient's condition then gradually improved.DiscussionThe dilemma of treating tuberculosis in liver disease is treating tuberculosis without ignoring hepatitis B and cirrhosis.ConclusionAdministration of anti-tuberculosis drugs based on liver tolerance of hepatotoxic drug in patients with hepatitis B and cirrhosis.
| S-EPMC9422211 | biostudies-literature
Project description:Background: Anti-tuberculosis drug-induced liver injury (ATB-DILI) is an adverse reaction with a high incidence and the greatest impact on tuberculosis treatment. However, there is a lack of effective biomarkers for the early prediction of ATB-DILI. Herein, this study uses UPLC‒MS/MS to reveal the plasma metabolic profile and lipid profile of ATB-DILI patients before drug administration and screen new biomarkers for predicting ATB-DILI. Methods: A total of 60 TB patients were enrolled, and plasma was collected before antituberculosis drug administration. The untargeted metabolomics and lipidomics analyses were performed using UPLC‒MS/MS, and the high-resolution mass spectrometer Q Exactive was used for data acquisition in both positive and negative ion modes. The random forest package of R software was used for data screening and model building. Results: A total of 60 TB patients, including 30 ATB-DILI patients and 30 non-ATB-DILI subjects, were enrolled. There were no significant differences between the ATB-DILI and control groups in age, sex, smoking, drinking or body mass index (p > 0.05). Twenty-two differential metabolites were selected. According to KEGG pathway analysis, 9 significantly enriched metabolic pathways were found, and both drug metabolism-other enzymes and niacin and nicotinamide metabolic pathways were found in both positive and negative ion models. A total of 7 differential lipid molecules were identified between the two groups. Ferroptosis and biosynthesis of unsaturated fatty acids were involved in the occurrence of ATB-DILI. Random forest analysis showed that the model built with the top 30 important variables had an area under the ROC curve of 0.79 (0.65-0.93) for the training set and 0.79 (0.55-1.00) for the validation set. Conclusion: This study demonstrated that potential markers for the early prediction of ATB-DILI can be found through plasma metabolomics and lipidomics. The random forest model showed good clinical predictive value for ATB-DILI.
| S-EPMC9641415 | biostudies-literature
Project description:Transcriptional profiling of mycobacterium tuberculosis clinical isolates in China comparing extensively drug-resistant tuberculosis with drug sensitive one.
2009-04-04 | GSE15540 | GEO
Project description:Despite being relatively rare, anti-tuberculosis drug-induced liver injury (ATDILI) is a leading cause of acute liver failure and a major reason for treatment discontinuation, because of no specific and selective markers for ATDILI. Herein, this study aimed to investigate whether telomere length, a biological indicator of age-related diseases, is associated with ATDILI outcomes and could serve as an early ATDILI biomarker. Relative telomere length (RTL) in blood leukocyte of 100 age- and gender-matched healthy controls, 49 tuberculosis patients with ATDILI, and 53 tuberculosis patients with non-ATDILI was quantified using real-time polymerase chain reaction. Both tuberculosis patients with and without ATDILI had significantly shorter RTL than healthy controls. Compared with tuberculosis patients with non-ATDILI, RTL in those with ATDILI was significantly increased. Longer RTL was found to be significantly associated with increased susceptibility to ATDILI. Multivariate linear regression analysis showed that an increment in RTL was independently correlated with elevated values of aspartate aminotransferase and alanine aminotransferase assessed within 60 days after anti-tuberculosis treatment. Kaplan-Meier curve analysis demonstrated that longer RTL was associated with elevated rates of hepatotoxicity in tuberculosis patients. Receiver-operating characteristic curve analysis unveiled a diagnostic accuracy of RTL as a novel indicator for ATDILI progression (AUC = 0.73), which yielded more sensitive and specific values than traditional liver biomarkers including serum enzyme activities of aminotransferases measured within 7 days after treatment with anti-tuberculosis regimens. Collectively, aberrant RTL in blood leukocyte would reflect hepatotoxicity induced by anti-tuberculosis agents and might have a potential biomarker for early ATDILI progression.
| S-EPMC7101399 | biostudies-literature