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Data on positive rechallenge in idiosyncratic drug-induced liver injury (DILI) are scarce. We aim to analyse the clinical presentation, outcome and drugs associated with positive rechallenge in two DILI registries. Cases from the Spanish and Latin American DILI registries were included. Demographics, clinical characteristics and outcome of cases with positive rechallenge according to CIOMS/RUCAM and current definitions were analysed. Of 1418 patients with idiosyncratic DILI, 58 cases had positive rechallenge (4.1%). Patients with positive rechallenge had shorter duration of therapy (p=0.001) and latency (p=0.003). In patients with rechallenge, aspartate transaminase levels were increased (p=0.026) and showed a prolonged time to recovery (p=0.020), albeit no differences were seen in terms of fatal outcomes. The main drug implicated in rechallenge was amoxicillin-clavulanate (17%). The majority of re-exposure events were unintentional (71%). Using both existing definitions of positive rechallenge, there were four cases which exclusively fulfilled the current criteria and five which only meet the historical definition. All cases of positive rechallenge, irrespective of the pattern of damage, fulfilled the criteria of either alanine transaminase (ALT) ≥3 times the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) ≥2 times ULN. Episodes of rechallenge were characterised by shorter duration of therapy and latency, and longer time to resolution, but did not show an increased incidence of fatal outcome. Based on our findings, ALT ≥3 times ULN and/or ALP ≥2 times ULN, regardless of the pattern of damage, is proposed as a new definition of rechallenge in DILI. [Display omitted] • Data on positive rechallenge in idiosyncratic drug-induced liver injury are scarce. • Positive rechallenge is characterised by shorter treatment duration and latency. • Poor outcome rates did no differ between first and rechallenged DILI episodes. • Evidence-based definition of rechallenge is proposed ALT≥3 ULN and/or ALP≥2 ULN. [ABSTRACT FROM AUTHOR]

In the current article the aims for a constructive way forward in Drug-Induced Liver Injury (DILI) are to highlight the most important priorities in research and clinical science, therefore supporting a more informed, focused, and better funded future for European DILI research. This Roadmap aims to identify key challenges, define a shared vision across all stakeholders for the opportunities to overcome these challenges and propose a high-quality research program to achieve progress on the prediction, prevention, diagnosis and management of this condition and impact on healthcare practice in the field of DILI. This will involve 1. Creation of a database encompassing optimised case report form for prospectively identified DILI cases with well-characterised controls with competing diagnoses, biological samples, and imaging data; 2. Establishing of preclinical models to improve the assessment and prediction of hepatotoxicity in humans to guide future drug safety testing; 3. Emphasis on implementation science and 4. Enhanced collaboration between drug-developers, clinicians and regulatory scientists. This proposed operational framework will advance DILI research and may bring together basic, applied, translational and clinical research in DILI. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical usefulness of the results obtained with (18)F-FDG PET/CT in relation to CT in the preoperative staging of patients with peritoneal carcinomatosis secondary to primary or recurrent ovarian cancer candidates to cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC).Material and Methods: A retrospective study comparing the results obtained with CT and (18)F-FDG PET/CT in the preoperative evaluation of a series of 59 patients was performed. In all patients the peritoneal carcinomatosis index (PCI) was determined by preoperative radiological CT and 18F-FDG PET/CT and compared with surgical PCI, which was considered as reference.Results: Of the 59 patients studied, in 55 peritoneal carcinomatosis presences were confirmed (4 patients had complete responses to neoadjuvant chemotherapy). The mean surgical, CT and 18F-FDG PET/CT PCI was 9.46±7.70, 3.69±3.96 and 2.25±1.02, respectively. In the global disease detection, CT showed a higher positive likelihood ratio (LR+) than (18)F-FDG PET/CT (15.3, 95% CI 8.35-28.04 vs. 3.47, 95% CI 3.36-5.11) and a lower negative likelihood ratio (LR-) than 18F-FDG PET/CT (0.67, 95% CI 0.61-0.73 vs. 0.82, 95% CI 0.76-0.88). In every region of the abdomen the CT showed a greater LR+ than 18F-FDG PET/CT and a lower LR- than 18F-FDG PET/CT.Conclusions: CT showed the best diagnostic results compared to (18)F-FDG PET/CT to confirme the presence of peritoneal disease. The lower performance of the (18)F-FDG PET/CT suggests that the main utility of (18)F-FDG PET/CT is to evaluate a possible metastatic extraperitoneal spread of the disease. [ABSTRACT FROM AUTHOR]

Background & Aims: Multiple instances of DILI in the same patient with drugs of similar structure or function as well as completely unrelated drugs are not well understood and poorly documented. We have sought evidence of the frequency and characteristics of patients who have experienced two DILI episodes due to different drugs. Methods: All cases of DILI systematically collected in the Spanish DILI Registry between 1994 and 2009 were retrieved. Data on demographics, clinical, laboratory and pathological findings, and outcome were analyzed. Results: Nine patients (mean age 67years, four women) out of 742, 1.21%, had evidence of two DILI episodes caused by different drugs. In four cases DILI was associated with structurally related drugs and in an additional two cases the drugs had a common target. In another case, unrelated antibiotics were implicated. In only two cases, the two drugs/herbals were not related in structure or function. All but one patient exhibited hepatocellular damage. The type of damage was consistent in both DILI episodes. Four cases presented as autoimmune hepatitis (AIH) in the second episode. Conclusions: Multiple episodes of DILI in association with different drugs occur infrequently. In each individual, the type of injury was similar during the two DILI episodes, regardless of the causative drug. Second episodes of DILI are more likely to be associated with features of AIH. It remains uncertain if this is drug-induced unmasking of true AIH or DILI with autoimmune features. These cases illustrate the dilemma faced by clinicians in distinguishing these possibilities. [Copyright &y& Elsevier]