June 6-7, 2017
Anyhoo, after coming down to earth, a tweet from @AASLD came through announcing content from the 2017 Drug-Induced Liver Injury Conference is ready to read over at the AASLD website. Off I went to see what I could see - for you and me.
What About The Conference?
In June, experts in clinical hepatology and toxicology gathered to share current information about drug-induced liver injury (DILI). For people outside the medical profession, navigating around this incredible information is time consuming, maybe even boring, unless you know where to look . So with that said, for those of you living with liver disease or viral hepatitis, I have highlighted a few points of interest to share with you.
Learning With Yogi
Well, on second thought, all the great information coming out of the conference isn't boring, some information is even pretty entertaining, for instance this presentation:Diagnosing DILI in Patients with Active or Advanced Underlying Liver Disease (with a little help from Yogi)
LINK
Download PDF
So What About HBV Reactivation Associated with HCV Therapy?
Yep, the conference covered that too. After PDF download, scroll down to the following topics: Reactivation of Hepatitis B in Trials with Immune Suppressive Drug and Detecting, and Evaluating Drug-Induced Liver Injury DILI with Active or Advanced Liver Disease; here is a quick summary.Opening First Session - Tuesday 6 June 2017
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Reactivation of Hepatitis B in Trials with Immune Suppressive Drug
Rajender Reddy
Lastly, I want to talk briefly about what's been going on in the hepatitis C field where there's been hepatitis B reactivation reported in the context of DAA therapy.
Detecting, Evaluating Drug-Induced Liver Injury DILI with Active or Advanced Liver Disease
Jim Lewis
Just to finish up. The non-DILI causes of jaundice and other events are more common than we think. Remember, DILI is uncommon. It's a rare event, but so many other things are more common. People get viral hepatitis, they have gallstone diseases, they have all of the other things that are listed here, all of which confuse someone who's looking at abnormal liver tests.
Of Interest
12 Detection and Management of DILI in NASH/NAFLD
Subjects – Naga Chalasani
As the NAFLD field has heated up, it has come up quite frequently that DILI is more common in patients with NAFLD. How do you monitor for it, given that there are baseline fluctuations in liver chemistries?
LINK - Begin here......
Easy Reading
Abstract I-6_2017: Detection and Evaluation of DILI in Patients with Chronic Liver Disease.
Download Abstract
The specific issue of detecting acute liver injury in patients with underlying chronic liver disease (CLD) and assigning causality to diagnose DILI remains challenging. The 2009 FDA Guidance FDA detecting and managing hepatotoxicity in patients in clinical trials did not provide any specifics in terms of dealing with patients with CLD. Recent clinical trials evaluating various therapies in patients with chronic hepatitis B, hepatitis C, NAFLD, PBC, malignancy (with hepatic metastases), among other disorders face the very real issue of assessing hepatic events in the setting of underlying liver disease, which brings with it a potentially different set of rules. As a result, clinicians and drug manufacturers have had to utilize what Dr Senior refers to as “medical reasoning” in order to determine if DILI has occurred, and how usual stopping rules should be modified using the currently available causality assessment methods. The topic at hand can be divided into the historical past, the present and the future.
LINK - Continue reading....
More Easy Reading
Session IV - Consortia for Best Practices to Reduce DILI
General Discussion of Issues [PDF]
4.1 The IQ Initiative
# 8. And we're all familiar with those areas. Patients with pre-existing liver diseases are very poorly covered by existing guidelines, and there are many questions regarding how to address drug-induced liver injury in these patients. It includes Hepatitis C, B, and NASH, and so on. Specific populations such as pediatric populations, geriatric population, oncology patients are, again, not well covered by existing guidelines or guidance or position papers. Non-hepatocellular DILI is a big topic. We are almost entirely focused on hepatocellular DILI, but there are 15 other types of drug-induced liver injury that we are not addressing. Specific drug groups are a big issue, such as immunosuppressant drugs, the group of chemotherapy-related immunotherapy. The question of drug re-challenge that is repeatedly being addressed, but there's no strong, clear guidelines for drug developers. And finally, the huge question of biomarkers is an ongoing question.
We All Know About This Website
4.4 LiverTox update and prospects
Okay, I was asked to give an update on LiverTox, which is an online website dedicated to drug-induced liver disease. It's been a collaborative effort between NIDDK and the National Library of Medicine, and is meant to be a source of reliable information on the clinical features, courses, and outcomes, and perhaps management of drug-induced liver disease due to both prescription and non-prescription medications, to herbal and dietary supplements. And its aims are to advance knowledge and support research.
# 8. So how did we come up with a list of drugs to be included in this? There's no one place that I know that you can go to that lists all the drugs that are available in the United States. We began with a list provided by the, ah, it's not a pointer, provided by the National Library of Medicine, a computerized list of 28,000 drugs, which was a little bit frightening at the time. But actually, most of them were multiples, like acetaminophen, there were over 1,000 drugs that include acetaminophen. There were unfortunately 700 varieties of OxyContin that you can purchase in America. So we took out all the duplicates, and we got down to a total of about 2,800 different compounds, chemical compounds.
And then going through those one at a time, we excluded those that were topical agents only. We excluded those that were very special. There were some like vaccines, plasma products, drugs that are not prescribed but are given in very rare situations. And also we took out veterinary medications and took out drugs that were not approved in the United States.
We came down with an initial master list of 900 different drugs, which was seen to be achievable. But in the interim, we've added more, we've added some HDS products, and we've added new agents as they're approved by the FDA each year, # 9. We currently have on my master list about 1236 agents. And as I said before, 1124 are on the website as of last week.
So here it is again, 1124 agents, about 91% of those on my list, master list. And if we take out the herbals and the nutritional supplements, the metals and so forth, we end up with around 1,000 different prescribed drugs. And looking those, there are some that are really similar, and you can group them together. For instance, all the estrogens we group as estrogens. All the anabolic steroids. Some drugs are actually just isomers of each other, like esomeprazole and omeprazole. We come down to what I think is about 941 different drugs.
LINK - Check Out LIVERTOX Website
4.7 Chinese DILIN experience
# 2. And as we all know, the incidence of DILI in the general population is not very high. The data from the United States suggests it's less 20 in 100 individuals. The data suggests the older the age, the higher the incidence. But one of the most important reasons behind this is the more prescriptions in older people.
# 3. Also, it is not so frequent in the general population. But in clinical practice, DILI is one of the most common reasons for no-cause liver injury or for a no-cause liver disease because the drug can cause all kinds of liver injury we have ever known. # 4. Some countries have reported their data. For example, the data from the United States and the European countries,
the most frequent agent to cause DILI is antibiotics. However, in the Asia region, like Korea or Singapore, the most frequent agent is herbals or the traditional Chinese medicines, TCMs.
LINK - Review above topics, download general discussion here....
Better yet, jump over the AASLD website and sift through vast amounts of information.
Enjoy the rest of your weekend! Bye Ira.
Tina
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