Ma Isabel Lucena

• MD, PhD
• University of Malaga

There is currently a need to investigate new biomarkers of acute liver injury (ALI) that are highly specific to the liver and capable of detecting early-stage liver damage. In this regard, circulating microRNAs (miRNAs), particularly microRNA122 (miRNA122), have recently been proposed as promising new candidate biomarkers. However, the quantificati...

Genetic susceptibility has been identified in idiosyncratic drug‐induced liver injury, a potentially severe adverse reaction towards drugs, herbal products and dietary supplements. However, its occurrence cannot be fully explained by the presence of genetic variants in specific genes, suggesting that other factors are involved. Drug‐induced liver i...

Genetic susceptibility has been identified in idiosyncratic drug‐induced liver injury, a potentially severe adverse reaction towards drugs, herbal products and dietary supplements. However, its occurrence cannot be fully explained by the presence of genetic variants in specific genes, suggesting that other factors are involved. Drug‐induced liver i...

Background and Aims Acute liver failure (ALF) is a serious condition, typically in individuals without prior liver disease. Drug‐induced ALF (DIALF) constitutes a major portion of ALF cases. Our research aimed to identify potential genetic predispositions to DIALF. Methods We analysed the potential genetic variants associated with DIALF using the...

The diagnosis of idiosyncratic drug‐induced liver injury (DILI) is a challenging task due to the lack of specific features or definitive diagnostic tools. A minimum of clinical and pharmacological information is required, together with laboratory and imaging tests to exclude other causes of liver injury. Several standardized methods have been devel...

Drug-induced liver injury (DILI) is a significant cause of acute liver failure (ALF) and liver transplantation in the Western world. Acetaminophen (APAP) overdose is a main contributor of DILI, leading to hepatocyte cell death through necrosis. Here, we identified that neddylation, an essential post-translational modification involved in the mitoch...

The elderly demographic is the fastest-growing segment of the world’s population and is projected to exceed 1.5 billion people by 2050. With multimorbidity, polypharmacy, susceptibility to drug–drug interactions, and frailty as distinct risk factors, elderly patients are especially vulnerable to developing potentially life-threatening safety events...

Drug‐induced liver injury (DILI) is a challenging liver disorder for hepatologists. We aimed to assess the pattern and causes of DILI in a tertiary hospital. We registered prospectively all patients referred with suspicion of DILI from 2018 to 2023. A total of 106 patients fulfilled the diagnostic criteria (30 caused by paracetamol were excluded; t...

Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have been consistently associa...

Idiosyncratic drug-induced liver injury (DILI) associated with drug reactions with eosinophilia and systemic symptoms (DRESS) is poorly characterized among patients of Western countries. We aimed to comprehensively assess the clinical characteristics, outcomes, and causative agents in a prospective, well-vetted cohort of DILI patients with DRESS (D...

Idiosyncratic drug-induced liver injury (DILI) is a complex and unpredictable event caused by different drugs, herbal, and dietary supplements. The early identification of human hepatotoxicity at the preclinical stages remains a major challenge, in which the selection of validated in vitro systems and test drugs has a significant impact. This syste...

A lack of biomarkers that detect drug-induced liver injury (DILI) accurately continues to hinder early- and late-stage drug development and remains a challenge in clinical practice. The Innovative Medicines Initiative’s TransBioLine consortium comprising academic and industry partners is developing a prospective repository of deeply phenotyped case...

Background and Aim The International Autoimmune hepatitis (AIH) Group retrospective registry (IAIHG-RR) is a web-based platform with subjects enrolled with a clinical diagnosis of AIH. As prognostic factor studies with enough power are scarce, this study aimed to ascertain data quality and identify prognostic factors in the IAIHG-RR cohort. Method...

Background Exposure to nonsteroidal anti‐inflammatory drugs (NSAIDs) such as ibuprofen (IBU) and naproxen (NAP) is associated with idiosyncratic drug‐induced liver injury (DILI). Carboxylate bioactivation into reactive metabolites (e.g., acyl glucuronides, AG) and resulting T‐cell activation is hypothesized as causal for this adverse event. However...

Background & aims: Idiosyncratic drug-induced liver injury (DILI) with autoimmune features is a liver condition with laboratory and histological characteristics similar to those of idiopathic autoimmune hepatitis (AIH), which despite being increasingly reported, remains largely undefined. We aimed to describe in-depth the features of this entity i...

Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article summarizes the major topics discussed at a joint International Conference held between Drug-Induced Liver Injury consortium and the International Autoimmune Hepatitis Group. DI-ALH...

The late event onset of a fraction of idiosyncratic drug-induced liver injury (DILI) cases and the link observed by genome-wide association studies (GWASs) of certain human leucocyte antigen (HLA) alleles with DILI due to specific drugs support the crucial role of the immune system (both innate and adaptive) in the pathogenesis of DILI. Recent adva...

Aims Detection and characterization of idiosyncratic drug‐induced liver injury (DILI) currently rely on standard liver tests, which are suboptimal in terms of specificity, sensitivity and prognosis. Therefore, DILI diagnosis can be delayed, with important consequences for the patient. In this study, we aimed to evaluate the potential of osteopontin...

Clostridioides difficile infection (CDI) appears to be associated with different liver diseases. C. difficile secretes membrane vesicles (MVs), which may be involved in the development of nonalcoholic fatty liver disease (NALFD) and drug-induced liver injury (DILI). In this study, we investigated the presence of C. difficile-derived MVs in patients...

Diagnosis of drug-induced liver injury (DILI) and its distinction from other liver diseases are significant challenges in drug development and clinical practice. Here, we identify, confirm, and replicate the biomarker performance characteristics of candidate proteins in patients with DILI at onset (DO; n = 133) and follow-up (n = 120), acute non-DI...

Introduction and Objectives: Idiosyncratic drug-induced liver injury (DILI) caused by antineoplastic and biological agents is an emerging clinical burden in oncologic patients. However, clinical characteristics of DILI due to these drugs remain poorly understood. This study aimed to assess the clinical presentation and outcome of DILI caused by ant...

Introduction and Objectives: Tyrosine kinases (TKs) are a family of proteins with a critical role in controlling cancer phenotypes, and many TK inhibitors (TKI) as anti-cancer agents are available. Mandatory black box warning has been issued for some TKI since 2012, and DILI is the most frequent adverse event quoted. This study aimed to describe th...

Introduction and Objectives: Although amoxicillin-clavulanate combination (ACC) is a well-established cause of liver injury, clinicians are unaware of some aspects that explain why its diagnosis may be initially missed, making the patient susceptible to unnecessary exploration or treatment. This study aimed to describe DILI characteristics linked t...

Introduction and Objectives: Drug-induced liver injury (DILI), usually considered rare, represents a unique challenge. The creation of DILI registries has improved epidemiological understanding and enhanced awareness, which in the absence of specific biomarkers, is essential for a more accurate diagnosis. This study aimed to present a complete anal...

Background The use of corticosteroids to treat patients with idiosyncratic drug‐induced liver injury (DILI) relies on empirical clinical decisions. Aim To investigate the relationship between corticosteroids and risk of acute liver failure (ALF) in patients with DILI and to assess if corticosteroid therapy was associated with improved outcomes in...

IntroductionDrug-induced liver injury is a significant health issue, yet the exposure-based incidence remains to be characterized.Objective We aimed to assess the frequency, phenotypes, and outcomes of acute liver injury associated with amoxicillin/clavulanate using a large electronic health record system.Methods Using the Veterans Health Administr...

BACKGROUND Drug-induced liver injury (DILI) due to amoxicillin–clavulanate (AC) has been associated with HLA-A*02:01, HLA-DRB1*15:01 and rs2476601, a missense variant in PTPN22. The aim of this study was to identify novel risk factors for AC-DILI and to construct a genetic risk score (GRS). METHODS Transcriptome-wide association (TWAS) and genome-...

Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregu...

Nitrofurantoin is a synthetic antibiotic that is recommended as first-choice treatment for uncomplicated urinary tract infections. The prescription of this drug has increased dramatically, especially in Latin American countries. We described the demographics, clinical characteristics, biochemical features, and outcome of nitrofurantoin-induced live...

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 fibro...

Background & Aims Liver injury with autoimmune features after vaccination against Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of patients with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Approach...

Introduction Idiosyncratic drug-induced liver injury (iDILI) is a challenging and unpredictable multifactorial condition. At present, validated preclinical models for the prediction of the hepatotoxic potential of a given drug are scarce. Areas covered This review intends to sum up the current knowledge about in vitro (including hepatocyte 2D cult...

IntroductionDrug-induced liver injury (DILI) is a rare but serious adverse event that can progress to acute liver failure (ALF). The evidence for treatment of DILI in children is scarce.Objective We aimed to comprehensively review the available literature on the therapies for both acetaminophen overdose (APAP) and idiosyncratic DILI in the paediatr...

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 tre...

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.e., the ability...

The gut microbiota could play a significant role in the progression of nonalcoholic fatty liver disease (NAFLD); however, its relevance in drug-induced liver injury (DILI) remains unexplored. Since the two hepatic disorders may share damage pathways, we analysed the metagenomic profile of the gut microbiota in NAFLD, with or without significant liv...

Background & aims: No multi-national prospective study of drug-induced liver injury (DILI) has originated from Europe. The design of a prospective European DILI registry, clinical features and short-term outcomes of the cases and controls is reported. Methods: Patients with suspected DILI were prospectively enrolled in the United Kingdom, Spain,...

Introduction: Idiosyncratic drug-induced liver injury (DILI) is a rare adverse reaction to drugs and other xenobiotics. DILI has different grades of severity and may lead to acute liver failure (ALF), for which there is no effective therapy. N-acetylcysteine (NAC) has been occasionally tested for the treatment of non-acetaminophen drug-induced ALF....

Chronic liver disease (CLD) is a leading health problem impacting the quality of life globally. China shares major global burden of CLD—including alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated fatty liver disease (MAFLD), and drug-induced liver injury (DILI), except for chronic viral hepatit...

Nitrofurantoin, minocycline, methyldopa and infliximab, have been found to induce autoimmune-like hepatitis (DI-AILH). Evidence for other drugs and herbal and dietary supplements (HDS) is unclear. The aims of the study were to establish criteria to define and review the published evidence of suspected DI-AILH. Search was undertaken in Pubmed using...

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 homeo...

In Spain, 1.5 million essential < 60-year-old workers were vaccinated with a first AstraZeneca vaccine dose. After assessing the cases of thrombosis with thrombocytopenia associated to this vaccine, the European Medicines Agency (EMA) supported the administration of 2 doses of the AstraZeneca vaccine with no age restrictions. Nevertheless, Spain de...

Acetaminophen (APAP) hepatotoxicity induces endoplasmic reticulum (ER) stress which triggers the unfolded protein response (UPR) in hepatocytes. However, the mechanisms underlying ER stress remain poorly understood, thus reducing the options for exploring new pharmacological therapies for patients with hyperacute liver injury. Eight-to-twelve-week-...

Background and aims: Roussel Uclaf Causality Assessment Method (RUCAM) for drug-induced liver injury (DILI) has been hindered by subjectivity and poor reliability. We sought to improve the RUCAM using data from the Drug-Induced Liver Injury Network (DILIN) and the Spanish DILI Registry, published literature and iterative computer modelling. Appro...

Background: Non-alcoholic fatty liver disease (NAFLD) and idiosyncratic drug-induced liver injury (DILI) could share molecular mechanisms involving the immune system. We aimed to identify activation immunological biomarkers in invariant natural killer T (iNKT) and CD4/CD8+ T cells in NAFLD and DILI. Methods: We analyzed the activation profile (C...

Drug‐induced liver injury (DILI) encompasses the unexpected damage that drugs can cause to the liver. DILI may develop in the context of an immunoallergic syndrome with cutaneous manifestations, which are sometimes severe (SCARs). Nevirapine, allopurinol, anti‐epileptics, sulfonamides, and antibiotics are the most frequent culprit drugs for DILI as...

Idiosyncratic drug-induced liver injury (iDILI) encompasses the unexpected harms that prescription and non-prescription drugs, herbal and dietary supplements can cause to the liver. iDILI remains a major public health problem and a major cause of drug attrition. Given the lack of biomarkers for iDILI prediction, diagnosis and prognosis, searching n...

The identification of specific HLA risk alleles in drug‐induced liver injury (DILI) points toward an important role of the adaptive immune system in DILI development. In this study, we aimed to corroborate the role of an adaptive immune response in DILI through immunophenotyping of leukocyte populations and immune checkpoint expressions. Blood samp...

Background Diagnosis of drug-induced liver injury (DILI) remains a significant challenge in interventional clinical trials during drug development and in clinical practice. We aimed to discover novel diagnostic biomarkers using proteomics and to evaluate their performance characteristics in distinguishing DILI from acute and chronic liver injury fr...

Introduction: Idiosyncratic DILI is a challenging condition, believed to involve the immune system. This hypothesis is supported by various identified HLA risk alleles. Objectives: To evaluate a potential role of the immune system in DILI through leukocyte immunophenotyping. Methods: Blood samples were collected from adjudicated DILI (n=12) and vir...

Introduction: In 2011, the Latin-American DILI-Network (LATINDILIN) set up under the guidance of the Spanish DILI Registry a network of hepatologists to prospectively identify and characterize DILI patients. Aim: To evaluate the drugs more frequently associated with DILI in LA, clinical phenotype and outcome. Methods: Demographics, clinical and bio...

Introduction Idiosyncratic drug-induced liver injury (DILI) is a complex hepatic condition whose diagnosis is challenging due to lack of specific biomarkers. Objectives We aimed to evaluate serum metabolomic differences between patients with DILI and with other causes of liver injury in search for specific DILI biomarkers. Methods Metabolomic pro...

Drug induced liver injury (DILI) is a major cause of acute liver failure (ALF) and one of the leading indications for liver transplantation in Western societies. Given the wide use of both prescribed and over the counter drugs, DILI has become a major health issue with a pressing need to find novel and effective therapies. Although significant prog...

Drug-induced liver injury (DILI) presentation varies biochemically and histologically. Certain drugs present quite consistent injury patterns, i.e., DILI signatures. In contrast, others are manifested as broader types of liver injury. The variety of DILI presentations by a single drug suggests that both drugs and host factors may contribute to the...

Background & aims: Although most drug-induced liver injury (DILI) cases resolve after the culprit medication is discontinued, time to recovery varies among patients, with 6-12% developing a chronic disease. Here, we investigated clinical factors and drug properties as potential risk determinants that influence the time course for DILI recovery and...

Nimesulide is a non-steroidal anti-inflammatory drug still marketed in many countries. We aim to analyze the clinical phenotype, outcome, and histological features of nimesulide-induced liver injury (nimesulide-DILI). We analyzed 57 cases recruited from the Spanish and Latin American DILI registries. Causality was assessed by the RUCAM scale. Mean...

Idiosyncratic drug-induced liver injury (DILI) is a type of hepatic injury caused by an uncommon drug adverse reaction that can develop to conditions spanning from asymptomatic liver laboratory abnormalities to acute liver failure (ALF) and death. The cellular and molecular mechanisms involved in DILI are poorly understood. Hepatocyte damage can be...

Simple Summary The study of cell features has historically been key for the progress of biological sciences and its relevance remains intact. In recent years, mass cytometry has emerged as a promising and powerful technology, capable of studying multiple parameters of cells in the same sample. Mass cytometry has been quickly applied to many researc...