Stanozolol-induced Liver Injury: A Distinctive Cholestatic Clinical and Biochemical Phenotype at Presentation.

Background & Aims: The misuse of Anabolic Androgenic Steroids (AAS), including Stanozolol, for performance enhancement has emerged as a significant cause of liver damage. This study aims to elucidate the distinctive hepatotoxicity profiles induced by Stanozolol.

Methods: Eighteen individuals were prospectively evaluated by the Latin American DILI Registry from 2013 to 2023.

Recreational Drugs and the Risk of Hepatocellular Carcinoma.

Recreational or aesthetic drug use is a distinctive behavior of humans, principally attested in the last century. It is known that recreational and illegal drugs are major contributors to the universal morbidity rate worldwide. Many of these substances have a well-established hepatotoxic potential, causing acute or chronic liver injury, liver fibrosis and cirrhosis, but their implications for hepatocellular carcinoma or other varieties of liver tumors are little known.

N-Acetylcysteine for Preventing Acetaminophen-Induced Liver Injury: A Comprehensive Review.

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. Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials.

Identification of New Toxicity Mechanisms in Drug-Induced Liver Injury through Systems Pharmacology.

Among adverse drug reactions, drug-induced liver injury presents particular challenges because of its complexity, and the underlying mechanisms are still not completely characterized. Our knowledge of the topic is limited and based on the assumption that a drug acts on one molecular target. We have leveraged drug polypharmacology, i.

Methionine Cycle Rewiring by Targeting miR-873-5p Modulates Ammonia Metabolism to Protect the Liver from Acetaminophen.

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.

Silymarin for Treating Toxic Liver Disease: International Consensus Recommendations.

Chronic liver disease (CLD) is a leading health problem impacting the quality of life globally. China shares a major global burden of CLD-including alcoholic liver disease, nonalcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease, and drug-induced liver injury, except for chronic viral hepatitis. Several exogenous toxins or endogenous metabolic insults trigger hepatic pathology toward steatosis, inflammation, and fibrosis, which, if left untreated, may culminate in liver cirrhosis.

Profile of herbal and dietary supplements induced liver injury in Latin America: A systematic review of published reports.

Hepatotoxicity related to HDS is a growing global health issue. We have undertaken a systematic review of published case reports and case series from LA from 1976 to 2020 to describe the clinical features of HDS related hepatotoxicity in this region. We search in PubMed, Web of Science, Scopus and specific LA databases according to PRISMA guidelines.

Differential hepatoprotective role of the cannabinoid CB and CB receptors in paracetamol-induced liver injury.

Background And Purpose: Protective mechanisms of the endogenous cannabinoid system against drug-induced liver injury (DILI) are actively being investigated regarding the differential regulatory role of the cannabinoid CB and CB receptors in liver fibrogenesis and inflammation.

Experimental Approach: The 2-arachidonoylglycerol (2-AG)-related signalling receptors and enzymatic machinery, and inflammatory/fibrogenic factors were investigated in the liver of a mouse model of hepatotoxicity induced by acute and repeated overdoses (750 mg·kg ·day ) of paracetamol (acetaminophen), previously treated with selective CB (ACEA) and CB (JWH015) agonists (10 mg·kg ), or lacking CB and CB receptors.

Key Results: Acute paracetamol increased the expression of CB , ABHD6 and COX-2, while repeated paracetamol increased that of CB and COX-2 and decreased that of DAGLβ.

Systematic review: ibuprofen-induced liver injury.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a leading cause of drug-induced liver injury (DILI) across the world. Ibuprofen is one of the most commonly used and safest NSAIDs, nevertheless reports on ibuprofen-induced hepatotoxicity are available.

Aim: To analyse previously published information on ibuprofen-induced liver injury for a better characterisation of its phenotypic expression.

Next-Generation Sequencing of Genes Reveals an Increased Frequency of Non-synonymous Variants Among Patients With NSAID-Induced Liver Injury.

The etiopathogenesis of drug-induced liver injury (DILI) is still far from being elucidated. This study aims to the study of genetic variations in DILI, related to the drug target, and specifically in the genes coding for the cyclooxygenase enzymes. By using Next-generation Sequencing we analyzed the genes coding for COX enzymes ( and ) in 113 individuals, 13 of which were patients with DILI caused by COX-inhibitors.

Protective role of c-Jun N-terminal kinase-2 (JNK2) in ibuprofen-induced acute liver injury.

Ibuprofen is a worldwide used non-steroidal anti-inflammatory drug which may cause acute liver injury (ALI) requiring liver transplantation. We aimed to unveil the molecular pathways involved in triggering ibuprofen-induced ALI, which, at present, remain elusive. First, we investigated activation of essential pathways in human liver sections of ibuprofen-induced ALI.

The mitochondrial negative regulator MCJ is a therapeutic target for acetaminophen-induced liver injury.

Acetaminophen (APAP) is the active component of many medications used to treat pain and fever worldwide. Its overuse provokes liver injury and it is the second most common cause of liver failure. Mitochondrial dysfunction contributes to APAP-induced liver injury but the mechanism by which APAP causes hepatocyte toxicity is not completely understood.

Toward a clinical practice guide in pharmacogenomics testing for functional polymorphisms of drug-metabolizing enzymes. Gene/drug pairs and barriers perceived in Spain.

The development of clinical practice recommendations or guidelines for the clinical use of biomarkers is an issue of great importance with regard to adverse drug reactions. The potential of pharmacogenomic biomarkers has been extensively investigated in recent years. However, several barriers to implementing the use of pharmacogenomics testing exist.

Assessment of nonsteroidal anti-inflammatory drug-induced hepatotoxicity.

Introduction: Liver toxicity related to NSAIDs is of outstanding importance because of the wide use of these drugs. NSAIDs are responsible for roughly 10% of the total of cases of drug-induced hepatotoxicity. The assessment of NSAID-induced hepatotoxicity, presently based on clinical and analytical biomarkers, is critical for early diagnosis and immediate withdrawal of the causing drug.

[Hepatotoxicity, a global problem with local features: toward the creation of a Pan-American Hepatotoxicity Network].

Drug-induced liver damage is one of the most complex liver diseases due to its similar presentation to other acute or chronic liver processes, its potential severity and the absence of specific biomarkers to confirm diagnosis, which is based on clinical suspicion and exclusion of alternative causes. Because the drug development process fails to completely screen out hepatotoxic molecules and identify susceptible individuals, postmarketing pharmacovigilance remains essential. Hepatotoxicity registries are the ideal instrument for systematic and continual data collection, using preestablished criteria based on consensus.

Antibiotic-induced liver toxicity: mechanisms, clinical features and causality assessment.

Antibiotics are the therapeutic agents most often associated with hepatotoxicity. However, this is mainly due to the widespread prescription of these drugs. The relative risk of antibiotic-related hepatotoxicity is low.

Rechallenge in drug-induced liver injury: the attractive hazard.

Progress in the understanding of drug-induced liver injury (DILI) is clearly hampered by the lack of specific markers of the disease. In this scenario, recrudescence of the liver injury upon re-exposure to the suspicious drug is considered the more reliable evidence of DILI. On-purpose re-exposure, however, entails both practical and ethical issues because the bulk of situations in clinical practice are non-immunoallergic DILI in which a provocation test frequently would give negative results.

Fatal acute hepatitis after sequential treatment with levofloxacin, doxycycline, and naproxen in a patient presenting with acute Mycoplasma pneumoniae infection.

Background: The diagnosis of drug-induced liver injury relies on comprehensive clinical assessments due to the absence of an established biomarker or pathognomonic features of liver histology. However, prompt recognition of a culprit drug as the cause of liver injury is the most important aspect in the management of hepatotoxicity.

Case Summary: A 63-year-old white male (85 kg) was admitted because of community-acquired pneumonia with associated pericarditis and subclinical hepatitis, subsequently related to acute Mycoplasma pneumoniae infection (diagnostic positive immuno-globulin M enzyme immunoassay, on hospital days 5 and 20).