Search results for "drug-induced liver injury"
showing 10 items of 10 documents
Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury
2017
Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify…
Clinical features and outcomes of patients with drug-induced autoimmune hepatitis: a retrospective cohort study.
2014
Abstract Background Drugs and herbal products can induce autoimmune hepatitis. We assessed frequency and clinical outcomes of patients suffering from drug-induced autoimmune hepatitis. Methods All patients with drug-induced liver injury admitted between 2000 and 2011 were retrospectively studied. Diagnoses of drug-induced autoimmune hepatitis and idiopathic autoimmune hepatitis were made according to simplified criteria. After discharge, all patients had regular follow-up and were contacted to update outcomes. Results Among 10,270 in-hospital patients, 136 (1.3%) were diagnosed with drug-induced liver injury. Among them, 12 (8.8%) were diagnosed as drug-induced autoimmune hepatitis (41.7% m…
Hepatitis E Virus Detection in Liver Tissue from Patients with Suspected Drug-Induced Liver Injury
2015
Hepatitis E virus (HEV) infection is increasingly recognized as a cause of acute hepatitis in the industrialized world. We aimed to determine the frequency of acute Hepatitis E virus (HEV) infection in cases of suspected drug-induced liver injury (DILI), mainly a diagnosis of exclusion. To this aim, formalin-fixed, paraffin-embedded (FFPE) liver tissues of all cases routinely processed in our institute during a 2 ½ years period in which DILI was amongst the differential diagnoses (157 liver biopsies, one liver explant) were subjected to semi-nested RT-PCR for the detection of hepatitis E virus (HEV) RNA. Histopathology was re-evaluated on all cases tested positive. HEV RNA was detectable in…
Rivaroxaban-induced hepatotoxicity
2017
Aim/Objective/Background Direct-acting oral anticoagulant drugs are marketed worldwide for the primary and secondary prevention and treatment of thromboembolic disorders. Rivaroxaban, an oral, direct factor Xa inhibitor, is one of the most used. Rivaroxaban-induced hepatotoxicity is unusual, although a number of adverse reports have recently been reported. Here, we report two new cases of rivaroxaban-induced hepatitis. Methods A systematic search of case reports on the MEDLINE database encompassing the years 2008–2016 was carried out.Additional references were obtained following a manual search of the retrieved papers. We report two new cases of adverse events occurred in patients treated w…
N-Acetylcysteine for Preventing Acetaminophen-Induced Liver Injury: A Comprehensive Review.
2022
Aims: N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to systematically review evidence of the use of NAC as a therapeutic option for APAP overdose and APAP-related DILI in order to define the optimal treatment schedule and timing to start treatment.Methods: Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials. The prespecified primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events (AEs).Results: In total, 34 studies of NAC usage in APAP-related DI…
A phenobarbital overdose: a case report
2017
Background: Phenobarbital is a long-acting barbiturate, responsible for many cases of poisoning, from unintentional overdose or attempted suicide. We report a case of phenobarbital overdose in a patient with history of depression. Patients and Methods: A 60 year old woman was admitted to our Internal Medicine Unit for drowsiness, irritability, difficulties in the maintenance of an upright position, dysphasia and weakness. She was suffering from depression and epilepsy and treated with phenobarbital 150 mg/die. Results: At the admittance, she had high fever and neck stiffness; phenobarbital serum levels were 71.2 mcg/ml (3 times u.n.l.); aminotransferases were 12-17u.n.l. Arterial blood pres…
miR-15a-3p Protects Against Isoniazid-Induced Liver Injury via Suppressing N-Acetyltransferase 2 Expression
2021
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. N-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 NAT2 expression and INH-induced liver injury via a series of in silico, in vitro, and in vivo analyses. Four mature miRNAs, including hsa-miR-15a-3p, hsa-miR-628-5p, hsa-miR-1262, and hsa-miR-3132, were predicted to …
Methionine Cycle Rewiring by Targeting miR-873-5p Modulates Ammonia Metabolism to Protect the Liver from Acetaminophen
2022
Drug-induced liver injury (DILI) development is commonly associated with acetaminophen (APAP) overdose, where glutathione scavenging leads to mitochondrial dysfunction and hepatocyte death. DILI is a severe disorder without effective late-stage treatment, since N-acetyl cysteine must be administered 8 h after overdose to be efficient. Ammonia homeostasis is altered during liver diseases and, during DILI, it is accompanied by decreased glycine N-methyltransferase (GNMT) expression and S-adenosylmethionine (AdoMet) levels that suggest a reduced methionine cycle. Anti-miR-873-5p treatment prevents cell death in primary hepatocytes and the appearance of necrotic areas in liver from APAP-adminis…
The use of same in chemotherapy-induced liver injury
2018
Drug-induced liver injury (DILI) remains the most common cause of acute liver failure in the Western world. Chemotherapy is one of the major class of drugs most frequently associated with idiosyncratic DILI. For this reason, patients who receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs may not be appropriate and which drug doses should be modified. S-adenosylmethionine (SAMe) is an endogenous agent derived from methionine. Its supplementation is effective in the treatment of liver disease, in particular intrahepatic cholestasis (IHC). The target of this review is to analyze the mechanisms of hepatotoxicity of the principal antican…
Optimizing diagnostic approach to drug-induced liver injury
2018
Drug-induced liver injury (DILI) is often a trial even to expert clinicians, because sometimes diagnosis is not easy to be made. Guidelines of the American College of Gastroenterology (ACG) yielded in 2014, help to better understand the problem. The diagnosis of DILI is made through a detailed evaluation of clinical, serological, radiological and histological aspects. Biochemical data include liver function tests that allow to assess the pattern of damage, such as hepatocellular, cholestatic and mixed liver injury; serological data include testing for major and possibly minor hepatotropic viruses, non-organ specific autoantibodies. Clinical scenario might include jaundice, nausea, vomiting …