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Journal ArticleDOI

Drug-Induced Liver Injury: An Analysis of 461 Incidences Submitted to the Spanish Registry Over a 10-Year Period

TL;DR: Patients with drug-induced hepatocellular jaundice have 11.7% chance of progressing to death or transplantation, and amoxicillin-clavulanate stands out as the most common drug related to DILI.
About: This article is published in Gastroenterology.The article was published on 2005-08-01. It has received 811 citations till now. The article focuses on the topics: Transplantation & Hy's law.
Citations
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TL;DR: The clinical care for patients with cholestatic liver diseases has advanced considerably during recent decades thanks to growing insight into pathophysiological mechanisms and remarkable methodological and technical developments in diagnostic procedures as well as therapeutic and preventive approaches.

1,405 citations

Journal ArticleDOI
TL;DR: To survey the burden of liver disease in Europe and its causes 260 epidemiological studies published in the last five years were reviewed and found each of these four major causes is amenable to prevention and treatment.

1,052 citations

Journal ArticleDOI
TL;DR: Clinical guidance is provided with regard to the detection, evaluation, and possible prevention of drug-related hepatotoxicity in patients exposed to hepatotoxic effects of new medication.
Abstract: Given its rarity, drug-related hepatotoxicity may not be seen during the initial clinical trials of a new medication. After approval, when many more patients are exposed, toxic effects that are very infrequent may emerge. This review explains the difficulties in identifying the cause of hepatotoxic effects in such situations and provides clinical guidance with regard to the detection, evaluation, and possible prevention of drug-related hepatotoxicity.

944 citations

Journal ArticleDOI
TL;DR: The current understanding of the pathophysiology of experimental drug hepatotoxicity is examined, focusing on acetaminophen, particularly with respect to the role of the innate immune system and control of cell-death pathways, which might provide targets for exploration and identification of risk factors and mechanisms in humans.
Abstract: The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the most frequent cause of post-marketing warnings and withdrawals This review examines the clinical signatures of this problem, signals predictive of its occurrence (particularly of more frequent, reversible, low-grade injury) and the role of monitoring in prevention by examining several recent examples (for example, troglitazone) In addition, the failure of preclinical toxicology to predict idiosyncratic reactions, and what can be done to improve this problem, is discussed Finally, our current understanding of the pathophysiology of experimental drug hepatotoxicity is examined, focusing on acetaminophen, particularly with respect to the role of the innate immune system and control of cell-death pathways, which might provide targets for exploration and identification of risk factors and mechanisms in humans

926 citations

Journal ArticleDOI
TL;DR: This report summarizes the causes, clinical features, and outcomes from the first 300 patients enrolled in a prospective study to recruit patients with suspected idiosyncratic drug-induced liver injury and create a repository of biological samples for analysis.

775 citations

References
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Journal ArticleDOI
TL;DR: The primary aim was to compare presenting clinical features and liver transplantation in patients with acute liver failure related to acetaminophen hepatotoxicity, other drugs, indeterminate factors, and other causes.
Abstract: Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent causes of acute liver failure. The cause of liver failure and coma grade at admission were...

1,988 citations

Journal ArticleDOI
TL;DR: In this paper, a new method for drug causality assessment is described and applied to reports of acute liver injuries, using reports with positive rechallenge as external standard.

1,291 citations

Journal ArticleDOI
Bénichou C1
TL;DR: An international meeting was organized to test the feasibility of adapting for international use the outcome of the French consensus meetings on drug-induced liver disorders, and resulted in a series of proposed standard designations of drug- induced liver disorders and criteria of causality assessment.

1,055 citations

Book
01 Jan 1978
TL;DR: The hepatotoxic effects of oncotherapeutic and immunosuppressive agents miscellaneous drugs and diagnostic chemicals afterthoughts on hepatotoxicity appendices are described.
Abstract: Part 1 General considerations: the spectrum of hepatotoxicity hepatic metabolism of foreign compounds vulnerability of the liver to toxic injury expressions of hepatotoxicity classification of hepatotoxins and mechanisms of toxicity hepatotoxic effects of ethanol chemical hepatocarcinogenesis. Part 2 Experimental hepatotoxicity: experimental hepatotoxicity direct hepatotoxins - haloaliphatics, phosphorus, iron and copper indirect cytotoxic hepatotoxins toxic cholestasis. Part 3 Environmental hepatotoxicity: syndromes of environmental hepatotoxicity occupational toxicity hepatotoxicity in the household the hepatotoxic potential of a polluted environment. Part 4 Iatrogenic hepatic injury: drug-induced liver disease anaesthetic agents psychotropic and anticonvulsant agents drugs used to treat rheumatic and musculospastic disease hormonal derivatives and related drugs hepatic injury from the treatment of infectious and parasitic diseases drugs used in cardiovascular disease hepatotoxic effects of oncotherapeutic and immunosuppressive agents miscellaneous drugs and diagnostic chemicals afterthoughts on hepatotoxicity appendices.

849 citations

Journal Article
TL;DR: The influence of older age in the cholestatic/mixed expression of the liver injury, as well as the independent association of female gender, older age, aspartate aminotransferase levels/hepatocellular type of damage and high bilirubin levels with the risk of fulminant liver failure/death are underlined.
Abstract: Pharmaceutical preparations, but also herbal products and dietary supplements, are emerging contributors to severe forms of liver disease, with hepatotoxicity ranking as the most frequent cause for acute liver failure. Although acetaminophen intoxication is still the reason for many severe cases of druginduced liver injury, the bulk of hepatic reactions to drugs are idiosyncratic. Indeed, the rarity of this serious adverse event prevents its detection in clinical trials. Therefore, in order to collect reliable data, prospective post-marketing studies are needed, especially with commonly used drugs that have been shown to be associated with drug-induced liver injury. Recently, different databases have described acetaminophen, antibiotics, nonsteroidal anti-inflammatory drugs, and anticonvulsants as being associated with drug-induced liver injury. Clinical presentations of drug-induced liver injury include predominantly a hepatocellular type of damage, yet cholestatic and mixed types are also common, the determinants of the type of damage induced by a given drug being poorly understood. Recent analysis of pooled data has underlined the influence of older age in the cholestatic/mixed expression of the liver injury, as well as the independent association of female gender, older age, aspartate aminotransferase levels/hepatocellular type of damage and high bilirubin levels with the risk of fulminant liver failure/death. In the long-term (proving the patient survives to the initial episode) cholestatic mixed type of damage is more prone to become chronic, while in the hepatocellular pattern the severity is greater, with further likelihood of evolution to cirrhosis. Cardiovascular and central nervous system drugs have been found to be the main groups leading to chronic liver damage. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug’s hepatotoxic potential, the exclusion of alternative causes of liver damage, and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide,

750 citations

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