Hepatoxicity SIG (Feb 24): DILI in patients with underlying liver disease- risks, potential mechanisms, and impact-DILI in patients with underlying liver disease- risks, potential mechanisms, and impact

Video Transcription

Video Summary

In the seminar for February by the Hepatotoxicity SIG, Dr. Nagachala Sani, a prominent figure in gastroenterology and hepatology, delivers a comprehensive presentation on the complexities of drug-induced liver injury (DILI), especially in the context of chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and cirrhosis. Dr. Sani highlights the challenges of idiosyncratic DILI, emphasizing the rare but impactful nature of such injuries. He delves into the intricacies of drug metabolism alterations in chronic liver diseases, pointing out that these diseases can significantly alter drug pharmacokinetics, thus influencing DILI risk.<br /><br />Dr. Sani presents evidence suggesting a dose-response relationship even for idiosyncratic DILI, which contrasts with the traditional view that such responses are not dose-dependent. He cites epidemiological studies indicating that chronic liver diseases may indeed increase the risk for DILI. He also addresses the poorer outcomes often seen when DILI occurs in patients already suffering from liver diseases, compared to those with healthy liver function. Moreover, the talk discusses the regulatory challenges and how drug development and testing might consider these risk factors differently.<br /><br />Through various examples, including clinical cases and data from the Drug-Induced Liver Injury Network (DILIN), Dr. Sani illustrates how underlying diseases can make the liver more susceptible to injury from certain medications. He advocates for closer scrutiny of drug concentrations during trials and encourages sharing concentration data to better understand and address DILI. The session concludes with engaging discussions from experts, enriching the dialogue around DILI in chronic liver conditions.

Keywords

Hepatotoxicity

Drug-induced liver injury

Chronic liver diseases

NAFLD

Cirrhosis

Idiosyncratic DILI

Drug metabolism

Pharmacokinetics

Dose-response relationship

Drug-Induced Liver Injury Network

Regulatory challenges