921 CONTRIBUTION OF DRUG-INDUCED LIVER INJURY (DILI) IN LIVER TRANSPLANTATION (OLT) INDICATION FOR ACUTE LIVER FAILURE (ALF) IN ADULTS IN FRANCE

BACKGROUND: Acute liver failure is a rare condition in which massive liver injury is associated with the rapid development of hepatic encephalopathy. Although viral hepatitis and drug-induced liver injury are the most common causes, no specific etiology is found in a substantial proportion of cases reported from Europe and the United States.AIM: To determine the etiology and outcome of patients with acute liver failure in the authors’ institution.PATIENTS AND METHODS: The charts of 81 consecutive patients admitted to Saint-Luc between 1991 and 1999 were reviewed.RESULTS: The etiology was viral in 27 cases (33.2%), toxic or drug-induced in 22 (27.2%), of unknown origin in 22 (27.2%) and due to various causes in 10 (12.3%) (autoimmune, vascular, cancer). Of the 81 patients, 16% survived without liver transplantation, and 84% died or underwent liver transplantation. Survival without liver transplantation differed according to the mode of presentation: the survival rate was 27% in patients with hyperacute liver failure, 7% in those with acute liver failure and 0% in those with subacute liver failure. Among the 38 patients who underwent liver transplantation, survival one year after transplantation was 71%. In the 30 patients who died without liver transplantation, the main causes of death were cerebral edema and sepsis.CONCLUSIONS: Acute liver failure is associated with a high mortality, and liver transplantation is the treatment of choice. In a significant proportion of cases, the etiology remains undetermined and is probably related to yet unidentified hepatotropic viruses.

Download Full-text

PP025—Improving hy’s law definition to better predict the risk of developing acute liver failure in drug-induced liver injury (DILI)

Clinical Therapeutics ◽

10.1016/j.clinthera.2013.07.060 ◽

2013 ◽

Vol 35 (8) ◽

pp. e25

Author(s):

M. Robles-Díaz ◽

C. Stephens ◽

I. Medina-Cáliz ◽

A.F. González ◽

A. González-Jiménez ◽

...

Keyword(s):

Liver Injury ◽

Liver Failure ◽

Acute Liver Failure ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Hy’S Law

Download Full-text

Correction: Cytokine profiles in acute liver injury—Results from the US Drug-Induced Liver Injury Network (DILIN) and the Acute Liver Failure Study Group

PLoS ONE ◽

10.1371/journal.pone.0212394 ◽

2019 ◽

Vol 14 (2) ◽

pp. e0212394 ◽

Cited By ~ 1

Author(s):

Herbert L. Bonkovsky ◽

Huiman X. Barnhart ◽

David M. Foureau ◽

Nury Steuerwald ◽

William M. Lee ◽

...

Keyword(s):

Liver Injury ◽

Liver Failure ◽

Acute Liver Failure ◽

Acute Liver Injury ◽

Study Group ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Cytokine Profiles ◽

The Us

Download Full-text

Use of Hy's Law and a New Composite Algorithm to Predict Acute Liver Failure in Patients With Drug-Induced Liver Injury

Gastroenterology ◽

10.1053/j.gastro.2014.03.050 ◽

2014 ◽

Vol 147 (1) ◽

pp. 109-118.e5 ◽

Cited By ~ 138

Author(s):

Mercedes Robles–Diaz ◽

M. Isabel Lucena ◽

Neil Kaplowitz ◽

Camilla Stephens ◽

Inmaculada Medina–Cáliz ◽

...

Keyword(s):

Liver Injury ◽

Liver Failure ◽

Acute Liver Failure ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Hy’S Law

Download Full-text

Necrotic cell death and suppression of T-cell immunity characterized acute liver failure due to drug-induced liver injury

Cytokine ◽

10.1016/j.cyto.2016.07.010 ◽

2016 ◽

Vol 86 ◽

pp. 21-28 ◽

Cited By ~ 5

Author(s):

Keisuke Kakisaka ◽

Kojiro Kataoka ◽

Yuji Suzuki ◽

Yohei Okada ◽

Yuichi Yoshida ◽

...

Keyword(s):

Cell Death ◽

Liver Injury ◽

Liver Failure ◽

Acute Liver Failure ◽

T Cell Immunity ◽

Necrotic Cell Death ◽

Necrotic Cell ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Cell Immunity

Download Full-text

Drug-Drug Combinations Can Enhance Toxicity as Shown by Monocyte-Derived Hepatocyte-like Cells From Patients With Idiosyncratic Drug-Induced Liver Injury

Toxicological Sciences ◽

10.1093/toxsci/kfz156 ◽

2019 ◽

Vol 171 (2) ◽

pp. 296-302 ◽

Cited By ~ 2

Author(s):

Andreas Benesic ◽

Kowcee Jalal ◽

Alexander L Gerbes

Keyword(s):

Liver Injury ◽

Liver Failure ◽

Drug Interactions ◽

Acute Liver Failure ◽

Causality Assessment ◽

Drug Combinations ◽

Positive Interactions ◽

In Vitro Test ◽

Drug Induced ◽

Drug Induced Liver Injury

Abstract Drug-induced liver injury (DILI) is a major cause for acute liver failure and regulatory actions on novel drugs. Individual patient characteristics are the main determinant of idiosyncratic DILI, making idiosyncratic DILI (iDILI) one of the most challenging diagnoses in hepatology. Individual drug-drug interactions might play a role in iDILI. However, the current approaches to iDILI diagnosis are focused on single drugs as causative agents. For the present analysis, 48 patients with acute liver injury who took 2 drugs and who were diagnosed as iDILI were investigated. A novel in vitro test was employed using monocyte-derived hepatocyte-like cells (MH cells) generated from these patients. iDILI diagnosis and causality were evaluated using clinical causality assessment supported by Roussel-Uclaf Causality Assessment Method. In 13 of these 48 patients (27%), combinations of drugs increased toxicity in the MH test when compared with the single drugs. Interestingly, whereas in 24 cases (50%) drug-drug combinations did not enhance toxicity, in 11 cases (23%) only the combinations caused toxicity. The incidence of severe cases fulfilling Hy’s law was higher in patients with positive interactions (57% vs 43%; p = .04), with acute liver failure occurring in 40% versus 8% (p = .01). The most common drug combinations causing increased toxicity were amoxicillin/clavulanate (8 of 9 cases) and diclofenac in combination with steroid hormones (4 of 9 cases). Drug-drug interactions may influence the incidence and/or the severity of idiosyncratic DILI. MH cell testing can identify relevant drug-drug interactions. The data generated by this approach may improve patient safety. Study identifier ClinicalTrials.gov NCT 02353455.

Download Full-text

Drug Hepatotoxicity

10.2310/gastro.14006 ◽

2018 ◽

Author(s):

Fernando Bessone ◽

Raúl J Andrade

Keyword(s):

Immune System ◽

Liver Injury ◽

Liver Failure ◽

Acute Liver Failure ◽

Causality Assessment ◽

Adaptive Immune System ◽

Genome Wide Association Studies ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Adaptive Immune

Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals, and dietary supplements) is an elusive liver disease presenting with a range of phenotypes and severity, including acute hepatitis that is indistinguishable from viral hepatitis, autoimmune hepatitis, steatosis, fibrosis or rare chronic vascular syndromes, asymptomatic liver test abnormalities,and acute liver failure. Case definition and characterization using liver biochemistry and histology are crucial for appropriate phenotyping. The incidence of DILI is probably higher than expected by the cases that are identified in clinical practice because of misdiagnosis and underreporting.The pathogenesis of DILI is complex, depending on the interaction of a drug’s physicochemical properties and host factors. Genome-wide association studies have identified several alleles from the major histocompatibility complex system, indicating a fundamental role of the adaptive immune system in DILI pathogenesis. As specific biomarkers for hepatotoxicity are still not available, the diagnosis of DILI remains one of exclusion of the alternative causes of liver damage. Structured causality assessment using the Roussel Uclaf Causality Assessment Method (RUCAM) or previously Council for International Organizations of Medical Sciences (CIOMS) instrument adds consistency to the diagnostic process, although there is room for improvement in the scale domains and score weighting. The therapy for idiosyncratic hepatotoxicity is supportive and relies on the prompt withdrawal of the offending agent. Corticosteroid therapy for hypersensitivity reactions or ursodeoxycholicacid for prolonged cholestasis is empirically used, although the degree of evidence is low. Existing databases have enabled a better prediction of immediate and long-term DILI prognosis. Multivariate models have identified clinical and analytical variables as predictive of acute liver failure and mortality as well as of chronic DILI. This review contains 2 figures, 5 tables, and 55 references Key Words: adaptive immune system; causality assessment; drug-induced liver injury; epidemiology; HLA alleles; pharmacogenetics; registries; risk factors

Download Full-text

Drug-induced liver injury

Emergencies in Gastroenterology and Hepatology ◽

10.1093/med/9780199231362.003.0018 ◽

2013 ◽

pp. 291-307

Author(s):

Daniel Marks ◽

Marcus Harbord

Keyword(s):

Oral Contraceptive ◽

Liver Injury ◽

Liver Failure ◽

Acute Liver Failure ◽

Oral Contraceptive Pill ◽

Herbal Remedies ◽

Drug Induced ◽

Herbal Products ◽

Contraceptive Pill ◽

Drug Induced Liver Injury

Drug-induced liver injury Paracetamol Statins NSAIDs and aspirin Anticonvulsants Antidepressants Amiodarone Anti-tuberculosis drugs Co-amoxiclav Minocycline Oral contraceptive pill Khat Herbal remedies Drug-induced liver injury (DILI) accounts for ~1% of general medical admissions, 〈5% of all cases of jaundice, but up to 30% of acute liver failure. It is associated with 〉1,000 medications and herbal products. The following principles apply: ...

Download Full-text