The role of the farnesoid X receptor in quadruple anti-tuberculosis drug-induced liver injury.

Anti-tuberculosis drugs-induced liver injury may be associated with the hepatic farnesoid X receptor (FXR). However, the relationship between isoniazid, rifampicin, pyrazinamide and ethambutol (HRZE) coadministration-induced liver injury and FXR has not been clarified. The purpose of this study was to clarify the role of FXR in HRZE-induced liver injury.

NAT2 and CYP2E1 polymorphisms and antituberculosis drug-induced hepatotoxicity in Peruvian patients.

Background: In Peru, 32,970 people were diagnosed with tuberculosis (TB) in 2019. Although TB treatment is effective, 3.4%-13% is associated with significant adverse drug reactions (ADR), considering drug-induced liver injury (DILI) as the most prevalent.

Chitosan Microparticles Loaded with New Non-Cytotoxic Isoniazid Derivatives for the Treatment of Tuberculosis: In Vitro and In Vivo Studies.

Lately, in the world of medicine, the use of polymers for the development of innovative therapies seems to be a major concern among researchers. In our case, as a continuation of the research that has been developed so far regarding obtaining new isoniazid (INH) derivatives for tuberculosis treatment, this work aimed to test the ability of the encapsulation method to reduce the toxicity of the drug, isoniazid and its new derivatives. To achieve this goal, the following methods were applied: a structural confirmation of isoniazid derivatives using LC-HRMS/MS; the obtaining of microparticles based on polymeric support; the determination of their loading and biodegradation capacities; in vitro biocompatibility using MTT cell viability assays; and, last but not least, in vivo toxicological screening for the determination of chronic toxicity in laboratory mice, including the performance of a histopathological study and testing for liver enzymes.

Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment-A Study from Patients of Portuguese Health Centers.

Drug-induced liver injury (DILI) is an unpredictable and feared side effect of antituberculosis treatment (AT). The present study aimed to identify clinical and genetic variables associated with susceptibility to AT-associated hepatotoxicity in patients with pulmonary tuberculosis treated with a standard protocol. Of 233 patients enrolled, 90% prospectively, 103 developed liver injury: 37 with mild and 66 with severe phenotype (DILI).

Isoniazid prophylaxis in liver transplant recipient with latent tuberculosis: Is it harmful for transplanted liver?

Background: Liver transplantation (LT) is considered the only treatment for patients with end-stage liver disease and, despite its incredible impacts on the patients' health status, places them in an immunocompromised state in which opportunistic infection would find a way to present. Latent tuberculosis infection (LTBI) is the most common form of TB and can be diagnosed through tuberculin skin test (TST) or Interferon-Gamma Release Assays (IGRA). LT recipients are at significant risk of TB activation.

Efficacy and safety of daily treatments for drug-susceptible pulmonary tuberculosis: a systematic review and network meta-analysis.

Objectives: To evaluate and update the evidence on the comparative efficacy and safety of antimicrobial drugs regimens for treating pulmonary drug-susceptible tuberculosis (DS-TB).

Methods: A systematic review was performed with searches in PubMed and Scopus (PROSPERO-CRD42019141463). We included randomised controlled trials comparing the effect of any antimicrobial regimen lasting at least 2 weeks.

A Case of Acute Liver Failure in a Patient on Isoniazid Prophylaxis for Latent Tuberculosis.

Isoniazid (INH) is widely used for latent despite the known risk of liver injury, with severe hepatitis occurring in up to 1% of patients. We report a patient who presented with two weeks of anorexia, nausea, and jaundice following six months of INH monotherapy for latent tuberculosis (TB). After other causes of liver injury were ruled out, she underwent a liver biopsy showing submassive necrosis, hepatocellular dropout, and lobular inflammation with no evidence of fibrosis.

Curcumin attenuates isoniazid-induced hepatotoxicity by upregulating the SIRT1/PGC-1α/NRF1 pathway.

As a serious infectious disease, tuberculosis threatens global public health. Isoniazid is the first-line drug not only in active tuberculosis but also in its prevention. Severe hepatotoxicity greatly limits its use.

Hepatotoxicity reports in the FDA adverse event reporting system database: A comparison of drugs that cause injury mitochondrial or other mechanisms.

Drug-induced liver injury (DILI) is a leading reason for preclinical safety attrition and post-market drug withdrawals. Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DILI, especially in idiosyncratic liver injury. This study examined liver injury reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) for drugs associated with hepatotoxicity mitochondrial mechanisms compared with non-mitochondrial mechanisms of toxicity.

Engineering a Ratiometric Photoacoustic Probe with a Hepatocyte-Specific Targeting Ability for Liver Injury Imaging.

In situ imaging of biological indicators is imperative for pathological research by utilizing an activatable photoacoustic (PA) probe. However, precise imaging in actual applications is hampered by the inevitable poor accumulation and low sensitivity. Herein, an amphiphilic molecular probe () was rationally constructed as proof of concept for in situ imaging of drug-induced liver injury, which consists of a hydrophilic target unit and a superoxide anion radical (O)-sensitive small-molecule PA moiety.

The cleavage kinetics of hydrazide derivatives of isoniazid by HPLC-UV/DAD and its impact on activity against Mycobacterium tuberculosis.

Isoniazid is a first-line drug for the treatment of tuberculosis, a bacterial disease caused by Mycobacterium tuberculosis. Its terminal amino group is highly reactive, leading to significant metabolic deactivation, drug interactions and hepatotoxicity. It is speculated that the activity of isoniazid derivatives is, in part, related to the cleavage of the protecting group.

Incidence of adverse drug events among patients on second line anti-tuberculosis regimen in the littoral region of cameroon.

Background: An adverse drug event (ADE) is an injury resulting from medical intervention associated with a drug. This study assesses the incidence of ADEs among participants on second-line drugs for tuberculosis (TB) in Cameroon.

Methods: This was a longitudinal observational study including 65 participants and carried out from January 2017 to December 2017.

miR-15a-3p Protects Against Isoniazid-Induced Liver Injury Suppressing -Acetyltransferase 2 Expression.

Isoniazid (INH), an effective first-line drug for tuberculosis treatment, has been reported to be associated with hepatotoxicity for decades, but the underlying mechanisms are poorly understood. -acetyltransferase 2 (NAT2) is a Phase II enzyme that specifically catalyzes the acetylation of INH, and NAT2 expression/activity play pivotal roles in INH metabolism, drug efficacy, and toxicity. In this study, we systematically investigated the regulatory roles of microRNA (miRNA) in expression and INH-induced liver injury via a series of , , and analyses.

Generation of a Transgenic Zebrafish Line for In Vivo Assessment of Hepatic Apoptosis.

Hepatic apoptosis is involved in a variety of pathophysiologic conditions in the liver, including hepatitis, steatosis, and drug-induced liver injury. The development of easy-to-perform and reliable in vivo assays would thus greatly enhance the efforts to understand liver diseases and identify associated genes and potential drugs. In this study, we developed a transgenic zebrafish line that was suitable for the assessment of caspase 3 activity in the liver by using in vivo fluorescence imaging.

Hepatotoxicity, efficacy and completion rate between 3 months of isoniazid plus rifapentine and 9 months of isoniazid in treating latent tuberculosis infection: A systematic review and meta-analysis.

Background: The mainstay therapy for latent tuberculosis infection is a 9-month regimen of daily isoniazid (9H) and a 3-month regimen of 12 once-weekly doses of isoniazid and rifapentine (3HP). We performed this updated meta-analysis to compare hepatotoxicity, efficacy and completion rate between these two regimens.

Methods: We searched all literature in the major medical databases using the subject search terms "isoniazid" and "rifapentine", and performed a systemic review and meta-analysis.