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Printable Handouts
Navigable Slide Index
- Introduction
- DILI topics to be discussed
- Magnitude of DILI
- What is DILI?
- Clinical syndromes (phenotypes) associated with DILI: one of the great Imitators in medicine
- Drug-Induced Liver Injury
- History of DILI through the decades
- History of DILI through the decades (cont.)
- Regulatory science and DILI
- DILI is rare but often dramatic
- DILI in drug development
- Causes of acute liver failure in the US
- Causes of acute liver failure and specific drug-induced causes in the U.S. acute liver failure study group*
- Epidemiology of DILI
- Epidemiology of DILI: population-based studies
- Epidemiology of DILI: more population-based studies
- DILI in mainland China
- Causes of acute DILI in the updated US DILIN registry
- Most common individual drugs implicated in the U.S. DILIN
- Top 25 drugs causing acute DILI in the U.S. DILIN account for two-thirds of all DILI cases
- Top causes of DILI from global registries
- Causes of DILI in mainland China among 25,927 hospitalized patients
- Historical mechanisms of DILI
- Acetaminophen overdose
- Acetaminophen (paracetamol) hepatotoxicity
- Acetaminophen undetected in plasma in >50% patients believed to have acute liver failure due to overdose
- Acetaminophen overdose: the differences between men and women
- Acetaminophen: well-defined hepatotoxic mechanism
- 2 historical types of idiosyncratic DILI
- Proposed third phenotype of DILI
- Expanded mechanisms of DILI
- Linking reactive metabolites and immune response causing iDILI
- Clinical adaptation (drug tolerance)
- Bile salt export pump and DILI
- Auto-immune-like DILI
- Clinical features of drug-induced autoimmune hepatitis vs. idiopathic AIH at Mayo Clinic
- Immune-mediated hepatitis
- Thank you for listening
Topics Covered
- History of Drug-Induced Liver Injury (DILI)
- Epidemiology of DILI
- Causes of acute liver failure
- Mechanisms of DILI
- Phenotypes of DILI
- Drug-induced autoimmune hepatitis, idiopathic autoimmune hepatitis, and immune-mediated hepatitis
Links
Series:
- Gastroenterology and Hepatology
- Periodic Reports: Advances in Clinical Interventions and Research Platforms
Categories:
Therapeutic Areas:
Talk Citation
Lewis, J.H. (2021, January 31). Drug-induced liver injury: importance, epidemiology, and mechanisms of DILI [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 21, 2024, from https://doi.org/10.69645/KVYQ9854.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. James H. Lewis has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Drug-induced liver injury: importance, epidemiology, and mechanisms of DILI
Published on January 31, 2021
46 min
Other Talks in the Series: Periodic Reports: Advances in Clinical Interventions and Research Platforms
Transcript
Please wait while the transcript is being prepared...
0:00
This is Dr. James H. Lewis.
I'm a professor of medicine and the Director of Hepatology in the division of
Gastroenterology at Georgetown University Medical Center, in Washington DC.
The topic for today's discussion is drug-induced liver injury (DILI):
where we've been, and where we are headed.
0:19
In the first part of my talk
I'm going to be discussing the importance of drug-induced liver injury, its epidemiology,
and the specific causes of drug-induced liver injury,
along with the mechanisms by which drugs can injure the liver.
In the second part of the talk
we'll be discussing risk factors for drug-induced liver injury,
including many of the host -
as well as pharmacologic - risk factors, along with
the recent research into pharmaco-genomic discovery.
The third part of the talk will include the rising incidence
of herbal and dietary supplement-related hepatotoxicity, and
the current methods by which we attempt to
diagnose DILI and the strategies used to treat and prevent DILI.
1:14
The magnitude of DILI is immense.
While it's rare to be seen in the clinic,
DILI's impact on drug development and
clinical practice is out of proportion to its incidence.
More than 700 drugs, herbal agents,
and chemicals have been implicated in causing drug-induced liver injury,
and it's the leading cause of
acute liver failure in the United States and other countries,
especially when we include acetaminophen (or paracetamol) as a cause.
It's also the leading cause of the failure to grant new drug approvals,
and has been the reason for withdrawal of new drugs in development.
About 7,000 DILI citations were cited between the year 2000 and 2009,
or about 700 annually.
Since then in the past decade,
over 6,000 citations were seen up to 2014, and currently
more than 1,500 publications dealing with drug-induced liver injury and
other aspects of hepatotoxicity have appeared annually since 2014.
What is drug-induced liver injury (DILI)?
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