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Drug-Induced Liver Injury Is a Major Risk for New Drugs
- Source :
- Digestive Diseases. 33:458-463
- Publication Year :
- 2015
- Publisher :
- S. Karger AG, 2015.
-
Abstract
- Drug-induced liver injury (DILI), a relatively rare condition, is nevertheless a major reason for not approving a drug in development or for removing one already marketed. With a specific diagnostic biomarker lacking, finding elevated serum enzyme [alanine aminotransferase (ALT), aspartate aminotransferase and alkaline phosphatase] activities remains an initial signal for incipient liver injury. Enzyme elevations alone may not be harmful, but if caused by a drug and followed by jaundice (called ‘Hy's law') there is a high possibility of serious DILI. In 1997 several drugs were approved by the Food and Drug Administration (FDA) of the USA that were later withdrawn from the market for serious liver toxicity. New drugs in development are now required to be monitored for liver injury, and the data is to be considered in the approval decision. A program called e-DISH (evaluation of drug-induced serious hepatotoxicity) was introduced in 2004 to aid medical reviewers to select from all subjects studied those few who show nontrivial liver injury and estimate the most likely cause. The threshold of enzyme elevation comprising a warning for possibly serious DILI is uncertain, although generally accepted as 3-5 times the ‘upper limit of normal'. The new direct-acting antiviral agents for treating chronic hepatitis C virus, which often lead to a reduction of elevated ALTs, mandate that a later increase without viral breakthrough be compared to the new on-treatment level of values. The drug may be discontinued or interrupted for evaluation to exclude other possible causes of liver injury. The FDA has approved no drug since 1997 that has been withdrawn later because of serious hepatotoxicity.
- Subjects :
- Drug
medicine.medical_specialty
media_common.quotation_subject
Pharmacology
Food and drug administration
Liver Function Tests
Internal medicine
medicine
Humans
Aspartate Aminotransferases
Drug Approval
media_common
Liver injury
biology
medicine.diagnostic_test
business.industry
Gastroenterology
Alanine Transaminase
General Medicine
Jaundice
Alkaline Phosphatase
medicine.disease
United States
Viral Breakthrough
Alanine transaminase
biology.protein
Drug Evaluation
Alkaline phosphatase
Chemical and Drug Induced Liver Injury
medicine.symptom
business
Liver function tests
Subjects
Details
- ISSN :
- 14219875 and 02572753
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Digestive Diseases
- Accession number :
- edsair.doi.dedup.....c3e67b83f6edd0a215ffdeed6d841794