gadoxetic-acid-disodium and Chemical-and-Drug-Induced-Liver-Injury

To describe Gd-EOB-DTPA-enhanced liver MR imaging findings in colon and rectal cancer patients who received Oxaliplatin.. Spectrum of hepatobiliary phase imaging findings include diffuse heterogeneous dysfunction, macronodular and micronodular FNH-like lesions, and coexistence of periportal increased liver function with FNH-like lesions. Differentiation of these benign lesions from metastasis is crucial to avoid biopsy in patients with colorectal cancers and may allow better understanding of sinusoidal obstruction syndrome pathophysiology and regenerative response of liver.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Colorectal Neoplasms; Contrast Media; Female; Fluorouracil; Gadolinium DTPA; Humans; Leucovorin; Liver Function Tests; Magnetic Resonance Imaging; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin

Background Safety data on routine clinical use of gadoxetate disodium for liver magnetic resonance imaging (MRI) is not reported yet. Purpose To assess the safety profile of gadoxetate disodium for liver MRI in the routine clinical setting. Material and Methods Six multicenter studies were performed in Europe, USA, Australia, and Asia to evaluate the safety and efficacy of gadoxetate disodium (Primovist®/Eovist®) enhanced liver MRI. Patients received a single intravenous bolus injection of the standard approved dose of 0.025 mmol/kg body weight (0.1 mL/kg). The number of patients, the characteristics of adverse events, related adverse events, and serious adverse events were analyzed. Results A total of 8194 patients were included in the database. A total of 141 patients (1.7%) reported 230 AEs of which 129 were considered being related to the use of gadoxetate disodium by the investigators. None of the AEs in the pediatric population ( n = 52) were related. The most frequent AEs independent of relationship to the drug included dyspnea (25/0.31%), nausea (22/0.27%), liver disorders (13/0.16%), and renal disorders (9/0.11%). Nine related SAEs were recorded. No patient died during the studies. Conclusion Gadoxetate disodium for liver MRI is safe and well tolerated in the routine clinical setting.

Topics: Adolescent; Adult; Age Distribution; Aged; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Contrast Media; Drug-Related Side Effects and Adverse Reactions; Dyspnea; Female; Gadolinium DTPA; Humans; Infant; Infant, Newborn; Internationality; Kidney Diseases; Liver Diseases; Magnetic Resonance Imaging; Male; Middle Aged; Nausea; Prevalence; Risk Factors; Sex Distribution; Treatment Outcome; Young Adult

Drug induced liver injury (DILI) is a major concern when developing new drugs. A promising biomarker for DILI is the hepatic uptake rate of the contrast agent gadoxetate. This rate can be estimated using a novel approach combining magnetic resonance imaging and mathematical modeling. However, previous work has used different mathematical models to describe liver function in humans or rats, and no comparative study has assessed which model is most optimal to use, or focused on possible translatability between the two species.. Our aim was therefore to do a comparison and assessment of models for DILI biomarker assessment, and to develop a conceptual basis for a translational framework between the species.. We first established which of the available pharmacokinetic models to use by identifying the most simple and identifiable model that can describe data from both human and rats. We then developed an extension of this model for how to estimate the effects of a hepatotoxic drug in rats. Finally, we illustrated how such a framework could be useful for drug dosage selection, and how it potentially can be applied in personalized treatments designed to avoid DILI.. Our analysis provides clear guidelines of which mathematical model to use for model-based assessment of biomarkers for liver function, and it also suggests a hypothetical path to a translational framework for DILI.

Topics: Animals; Biomarkers; Chemical and Drug Induced Liver Injury; Humans; Liver; Magnetic Resonance Imaging; Models, Theoretical; Rats

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by pyrrolizidine alkaloids(PAs)-containing herbals. In this study, the aim of our study was to investigate the imaging features of PAs-induced HSOS on gadoxetic acid-enhanced magnetic resonance imaging (MRI), susceptibility-weighted imaging(SWI) and T2* weighted imaging (T2* WI). We analyzed medical records and MR images of 28 PAs-induced HSOS patients enrolled from Feb, 2013, to Apr, 2017. Abnormal liver function was observed in most of the PAs-induced HSOS patients. Heterogeneity of liver parenchyma in hepatobillary phase (HBP) of gadoxetic acid-enhanced MR scan was observed in 100% of the PAs-induced HSOS patients. Distributional patterns of heterogeneous hypointensity were multifocal distribution (mild) in 4 patients (14.29%), multifocal distribution (severe) in 15 cases (53.57%), and diffuse distribution in 9 patients (32.14%). Hypointense in SWI and T2*WI was observed in the patients of PAs-induced HSOS, and the distribution of hypointense in SWI and T2*WI was similar to that of portal-venous phase of MR scan. The severity of heterogeneous hypointensity scored by volume fraction in hepatobillary phase of gadoxetic acid-enhanced MRI was positively correlated with PT and INR, the severity of hypointensity in HBP was a risk factor of death events. In conclusion: Heterogenous hypointensity of liver parenchyma was an imaging sign of hepatobillary phase in gadoxetic acid-enhanced MRI; thus, it will provide evidences for the diagnosis of PA-induced HSOS.

Topics: Aged; Chemical and Drug Induced Liver Injury; Contrast Media; Diffusion Magnetic Resonance Imaging; Drugs, Chinese Herbal; Female; Gadolinium DTPA; Hepatic Veno-Occlusive Disease; Humans; Liver; Liver Function Tests; Male; Middle Aged; Pyrrolizidine Alkaloids; Retrospective Studies

To retrospectively evaluate findings of chemotherapy-induced focal hepatopathy (CIFH) on gadoxetic acid-enhanced magnetic resonance (MR) and diffusion-weighted (DW) images and to determine imaging features that are most helpful in differentiating CIFH from metastasis.. This retrospective study was approved by the institutional review board, and informed consent was waived. MR images, including DW images and gadoxetic acid-enhanced images, from 12 patients (four men, eight women; age range, 25-64 years) with 15 CIFHs were reviewed independently and in consensus by two radiologists and were compared with those obtained in 20 control patients (12 men, eight women; age range, 32-84 years) with 30 hepatic metastasis who were matched for tumor size, primary organ, and chemotherapy regimen. Interobserver agreement was assessed with κ statistics, and univariate analysis was performed for comparisons. For quantitative analyses, apparent diffusion coefficients (ADCs) and lesion-to-liver contrast ratios (CRs) were measured. Histopathologic examinations were performed for CIFHs.. Histopathologic examination revealed that the development of CIFHs was attributable to accentuated manifestations of sinusoidal obstruction syndrome. Interobserver agreement was excellent (κ > 0.85). An ill-defined margin on hepatobiliary phase (HBP) images was the most discriminating independent variable in the differentiation of CIFH from metastasis (odds ratio, 16; P = .009). ADC and CR values in CIFH group were significantly higher than those in metastasis group (P < .001 and P = .041).. CIFH should be considered a mimicker of metastasis in patients with gastrointestinal malignancy during chemotherapy. CIFH can be differentiated from metastasis on the basis of gadoxetic acid-enhanced MR and DW imaging findings; an ill-defined margin on HBP images was especially characteristic.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Chemical and Drug Induced Liver Injury; Contrast Media; Diffusion Magnetic Resonance Imaging; Female; Fluorouracil; Gadolinium DTPA; Gastrointestinal Neoplasms; Humans; Image Interpretation, Computer-Assisted; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Retrospective Studies

Topics: Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Contrast Media; Gadolinium DTPA; Hepatectomy; Liver; Magnetic Resonance Imaging; Male; Rats; Rats, Wistar