June 4, 2023

Prof. Scott Friedman presents his Focus article for the Journal of Hepatology’s August 2014 issue.

Hi this is dr. scott freedman in new york here to discuss this month’s focus piece in the journal of hepatology which focuses on a very interesting and emerging field of pharmacogenomics and drug toxicity specifically i wrote the piece commenting on a very interesting article by clark and others studying the impact of genetics and fatty liver on the organic anion

Transporter a protein that is important for the disposition of statins in particular pravastatin this group has shown previously that genetics can influence the activity of this transporter and the disposition of pravastatin and specific variants may be linked to a heightened risk of myopathy and adverse events from this drug so to model these variants they used a

Mouse in which they knocked out the transporter and looked at the disposition of pravastatin and then combine that with a fatty liver disease model from the mcd diet now everybody knows that the mcd diet is not ideal as a diet for fatty liver disease but the authors have previously shown that the model recapitulates the human disposition of pravastatin so in this

Particular narrow indication it’s a useful model so when they combined genetic loss of the transporter with a fatty liver disease model they had a market increase in private statin concentrations and of course the implication is that under specific circumstances genetic variants may converge with fatty liver disease to heighten the risk of drug toxicity to the

Liver now this is a very important area and it speaks to the growing field of pharmacogenomics in other words how genetics impact on the disposition of drugs and therefore on the potential risk to liver toxicity this is a huge undertaking but of course drug-related liver toxicity is one of the most important complications of farmers pharmacokinetics and drug use in

The world and in fact more drugs are withdrawn from the market after licensing because of drug toxicity to the liver than any other reason so this is a really important area now what the authors have shown is that genetics plays a role that it’s variable but if we return to the human condition we do not know enough about how genetics impact on drug disposition and

Therefore we can’t predict with most cases why or how genetics contributes to drug-induced liver toxicity there are networks around the world that are trying to collect information to help elucidate this problem in the u.s. it’s the drug-induced liver injury network but there are comparable drug toxicity networks in europe and throughout the world which together

May be able to uncover genetic links to the risk for liver drug toxicity this is a huge undertaking but with the advancing ability of big data computing we’re hopeful that they’ll be progress in uncovering genetic links and they’ll for predicting the risk of liver drug toxicity now finally even if we have genetic predictors of toxicity how are we going to get

That information to practicing clinicians they’re not going to be reading very detailed descriptions of drug toxicity and genetic links and so there are efforts underway to create software that would effectively translate genetic information inferring or describing risk of particular drugs into the patient’s electronic medical record we’re just in the early days

Of such effort but one can imagine that eventually a patient will go to the doctor the doctor will prescribe a specific drug in the emr and an alert will sound or an alert will pop up that tells the clinician in this particular patient because of his or her genetics the dose needs to be changed or the risk of toxicity may be especially high so that’s where this

Field of pharmacogenomics is going both in terms of understanding the risk of genetics how that risk may be amplified if there’s underlying liver disease in particular fatty liver disease and ultimately translating complex genetic information into decision making by clinicians at the point of care we have a long way to go but the tools are in place and this is an

Extremely important problem that could save thousands of lives if we can avoid drug toxicity to the liver cause of genetic variants

Transcribed from video
Journal of Hepatology – August 2014 – Focus By Journal of Hepatology