Genetic and Genomic Approaches to the Study of Drug-Induced Liver Injury.

Idiosyncratic hepatotoxicity induced by prescribed drugs has been known since the early 20th century. Identifying risk factors, including genetic factors, that trigger this drug-induced liver injury (DILI) has been an important priority for many years, both to prevent drugs that cause liver injury being licensed and as a potential means of preventing at-risk patients being prescribed causative drugs. Improved methods for genomic analysis, particularly the development of genome-wide association studies, have facilitated the identification of genomic risk factors for DILI, but, to date, there are only two main examples, liver injury caused by amoxicillin-clavulanate (AC) and by flucloxacillin, where genetic risk factors causing the injury have been identified and replicated with understanding of the underlying mechanism.

A study of N-acetyltransferase 2 gene polymorphisms in the Indian population and its relationship with serum isoniazid concentrations in a cohort of tuberculosis patients.

The N-acetyltransferase 2 (NAT2) gene exhibits substantial genetic diversity, leading to distinct acetylator phenotypes among individuals. In this study, we determine NAT2 gene polymorphisms in tuberculosis (TB) patients and analyze serum isoniazid (INH) concentrations across the various genotypes. An observational prospective cohort study involving 217 patients with pulmonary or extrapulmonary TB was carried out.

Acute Liver Failure Caused by Isoniazid during Preventive Treatment for Latent Tuberculosis: A Rare Autopsy Case Report.

Treating patients with latent tuberculosis infection (LTBI) to prevent the development of tuberculosis is a fundamental treatment strategy in daily practice. Isoniazid (INH) therapy for 6-12 months is recommended. However, INH can also cause hepatotoxicity.

Preclinical liver toxicity models: Advantages, limitations and recommendations.

Experimental animal models are crucial for elucidating the pathophysiology of liver injuries and for assessing new hepatoprotective agents. Drugs and chemicals such as acetaminophen, isoniazid, valproic acid, ethanol, carbon tetrachloride (CCl), dimethylnitrosamine (DMN), and thioacetamide (TAA) are metabolized by the CYP2E1 enzyme, producing hepatotoxic metabolites that lead to both acute and chronic liver injuries. In experimental settings, acetaminophen (centrilobular necrosis), carbamazepine (centrilobular necrosis and inflammation), sodium valproate (necrosis, hydropic degeneration and mild inflammation), methotrexate (sinusoidal congestion and inflammation), and TAA (centrilobular necrosis and inflammation) are commonly used to induce various types of acute liver injuries.

Histopathological, immunohistochemical and physiological study for the hepatoprotective effect of melatonin against inhrifampicin-induced hepatotoxicity in mice model.

Objective: Aim: The purpose of this study is to assess the hepatoprotective ef f ect of melatonin against isoniazid (INH) and rifampicin (RMP) induced hepatotoxicity in albino mice.

Patients And Methods: Materials and Methods: Adult male mice were divided into four groups: saline, INH-RMP, INH-RMP+MT and MT were administered for 21 days. Biochemical analyses were performed for the determination of ALT, AST.

Tuberculosis Preventive Treatment for Pregnant People With Human Immunodeficiency Virus in South Africa: A Modeling Analysis of Clinical Benefits and Risks.

Background: Although prior studies of tuberculosis-preventive treatment (TPT) for pregnant people with human immunodeficiency virus (PPWH) report conflicting adverse pregnancy outcome (APO) risks, international guidelines recommend TPT for PPWH.

Methods: We used a microsimulation model to evaluate 5 TPT strategies among PPWH receiving antiretroviral therapy in South Africa: No TPT; 6 months of isoniazid (6H) or 3 months of isoniazid-rifapentine (3HP) during pregnancy (Immediate 6H or Immediate 3HP) or post partum (Deferred 6H or Deferred 3HP). The primary outcomes were maternal, fetal/infant, and combined deaths from causes potentially influenced by TPT (maternal tuberculosis, maternal hepatotoxicity, stillbirth, low birth weight [LBW], and infant tuberculosis).

Isoniazid prophylaxis based on tuberculosis risk factors in living kidney transplantation recipients: A retrospective cohort study.

Background: Tuberculosis (TB) is a major and severe opportunistic infection among solid organ transplant recipients. Chemoprophylaxis is advised for those with latent tuberculosis infection. However, the effectiveness of an isoniazid (INH) prophylactic approach based on TB risk factors remains uncertain.

Hypersensitivity myocarditis induced by isoniazid overdose in a 15-year-old girl: a case report.

Introduction: Myocarditis represents a diverse group of inflammatory diseases affecting the heart muscle, with both infectious and non-infectious etiologies. Among the non-infectious causes, drug-induced hypersensitivity reactions are rare but serious. Isoniazid, a cornerstone in tuberculosis treatment, is known for its hepatotoxicity but has rarely been documented to cause hypersensitivity myocarditis.

A true challenge: Disseminated tuberculosis with tuberculous meningitis in a patient with underlying chronic liver disease.

Tuberculous meningitis (TBM) is a potentially life-threatening form of tuberculosis (TB) that affects the central nervous system. Its management in patients with concomitant chronic liver disease (CLD) presents unique challenges due to altered drug metabolism with potentially impaired spinal fluid drug penetration and hepatotoxicity. The standard regimen for TBM includes isoniazid (INH) and rifampin (RIF), and Pyrazinamide (PZA) which are metabolized by the liver and may cause hepatotoxicity, which can exacerbate preexisting liver disease.

Strategies for isoniazid preventive therapy in HIV-positive patients who consume alcohol.

WHO guidance to defer isoniazid preventive therapy (IPT) among those with regular alcohol use because of hepatotoxicity concerns may exclude many people living with HIV (PLWH) at high TB risk in these settings.To evaluate hepatotoxicity during TB preventive therapy (TPT) in PLWH who report alcohol use in Uganda over 10 years.We developed a Markov model of latent TB infection, isoniazid preventive therapy (IPT - a type of TPT), and TB disease using data from the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) study.

*05:01 and *11:01 Is Associated with Adverse Drug Reactions to Isoniazid and Rifampin for Treatment of Latent Tuberculosis Infection in South Korea.

Screening and treating healthcare workers (HCWs) for latent tuberculosis infection (LTBI) are essential for tuberculosis (TB) infection control. Adverse drug reactions (ADRs) to anti-TB drugs present challenges to patient safety and treatment completion. This study investigated the association between human leukocyte antigen (HLA) alleles and the risk of ADRs, especially drug hypersensitivity (DHS) and hepatotoxicity, in HCWs with LTBI receiving isoniazid (INH) and rifampin (RIF) therapy.