Raúl J Andrade

• MD PhD FAASLD Professor of Medicine
• University of Malaga

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...

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...

Aim We aimed to assess the role of FGF21 in metabolic dysfunction‐associated steatotic liver disease (MASLD) at a multi‐scale level. Methods We used human MASLD pathology samples for FGF21 gene expression analyses (qPCR and RNAseq), serum to measure circulating FGF21 levels and DNA for genotyping the FGF21 rs838133 variant in both estimation and v...

Background and aim: The distinction of drug-induced liver injury (DILI), drug-induced autoimmune-like hepatitis (DI-ALH) and autoimmune hepatitis (AIH) can be challenging due to overlapping clinical characteristics. Recently, polyreactive immunoglobulin G (pIgG) was identified as a novel biomarker with a higher accuracy for the diagnose of AIH than...

Background Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is the recommended rescue therapy for patients with chronic hepatitis C infection who fail direct‐acting antivirals (DAAs). Data are limited on the effectiveness of this treatment after the current first‐line therapies. Our aim was to analyse the effectiveness and safety of SOF/VEL/V...

MASLD can manifest as hepatocellular damage, which can result in mild elevation of aminotransferases. However, in some patients, MASLD presents with cholestatic pattern. To assess the impact of the biochemical pattern on the natural course of MASLD, including liver damage in histology, the accuracy of non-invasive tests(NITs), and prognosis. Multic...

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...

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...

Background Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 dos...

Drug-induced liver injury (DILI) is an adverse reaction to drugs and other xenobiotics that can have serious consequences and jeopardise progress in pharmacological therapy. While DILI is predominantly hepatocellular, a non-negligible percentage of patients who present with cholestatic damage. Mixed damage is typically lumped together with cholesta...

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 & 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...

Background & aims An estimated 38% of adults worldwide have NAFLD. From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised research agenda for the global fatty liver disease community of practice. Methods Nine co-chairs drafted...

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...

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...

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) affect 17–46% of Western countries, making coexistence with other liver diseases inevitable. We investigated the prevalence and clinical significance of NAFLD/NASH or the components of metabolic syndrome (MetS) in a large multicentric cohort of patients with aut...

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...

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...

Introduction: The pandemic caused by SARS-CoV-2 has drastically changed the global health landscape. Our objective was to verify if, after the start of the pandemic, there was an increase in in-hospital mortality in patients admitted to a Gastroenterology Service of a 3rd level hospital. Material and methods: The 1039 admissions registered at the V...

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...

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...

Background and objective The emergence of highly tolerable, effective, and shorter duration direct-acting antivirals (DAAs) regimens offers the opportunity to simplify hepatitis C virus management but medical costs are unknown. Thus, we aimed to determine the direct medical costs associated with a combo-simplified strategy (one-step diagnosis and l...

Resumen Background: Hepatocellular carcinoma (HCC) represents 75%-85% of all primary liver cancers and the third most common cause of cancer-related death worldwide. Cirrhosis is the most relevant risk factor for HCC with 70%-90% of cases diagnosed at end-stage liver disease. Several studies have revealed that early diagnosis of HCC under surveilla...

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...

Background: A variant (p.Arg225Trp) of peroxisomal acyl-CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27-BAs, mainly trihydroxycholestanoic acid (THCA). Aims: To investigate the prevalence of ACOX2 deficiency-associated hypertrans...

The main aim was to evaluate changes in urea cycle enzymes in NAFLD patients and in two preclinical animal models mimicking this entity. Seventeen liver specimens from NAFLD patients were included for immunohistochemistry and gene expression analyses. Three-hundred-and-eighty-two biopsy-proven NAFLD patients were genotyped for rs1047891, a function...

Background & aims The impact of recurrent autoimmune hepatitis (AIH) post-liver transplant on patient and graft survival is not well characterised. We evaluated a large, international multi-center cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft sur...

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-...

Autoimmune hepatitis (AIH) has been well characterized and codified through the development of diagnostic criteria. These criteria have been adapted and simplified and are widely used in clinical practice. However, there is a need to update and precisely define the criteria for both treatment response and treatment. We performed a systematic review...

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...

Patients with decompensated cirrhosis, particularly those with acute‐on‐chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characterist...

Chronic viral hepatitis infection affects an estimated 325 million people globally. People who initiate treatment after significant disease progression face increased risk of severe liver complications and death. Data are scarce on the characteristics and risk factors of people who present late to care in Spain and globally. Data were collected fro...