Antibiotics and Liver Injury | Arthritis Information

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Antibiotics are the single largest class of agents that cause idiosyncratic drug-induced liver injury (DILI), reports a new study in Gastroenterology, an official journal of the American Gastroenterological Association (AGA) Institute. DILI is the most common cause of death from acute liver failure and accounts for approximately 13 percent of cases of acute liver failure in the U.S. It is caused by a wide variety of prescription and nonprescription medications, nutritional supplements and herbals.

"DILI is a serious health problem that impacts patients, physicians, government regulators and the pharmaceutical industry," said Naga P. Chalasani, MD, of the Indiana University School of Medicine and lead author of the study. "Further efforts are needed in defining its pathogenesis and developing means for the early detection, accurate diagnosis, prevention and treatment of DILI."

In this prospective, ongoing, multi-center observational study - the largest of its kind - patients with suspected DILI were enrolled based upon predefined criteria and followed for at least six months. Those with acetaminophen liver injury were excluded.

Researchers found that DILI was caused by a single prescription medication in 73 percent of the cases, by dietary supplements in 9 percent and by multiple agents in 18 percent. More than 100 different agents were associated with DILI; antimicrobials (45.5 percent) and central nervous system agents (15 percent) were the most common. Of the dietary supplements causing DILI, compounds that claim to promote weight loss and muscle building accounted for nearly 60 percent of the cases. The study found that at least 20 percent of patients with DILI ingest more than one potentially hepatotoxic agent.

DILI remains a diagnosis of exclusion and thus detailed testing should be performed to exclude competing causes of liver disease; importantly, acute hepatitis C virus (HCV) infection should be carefully excluded in patients with suspected DILI by HCV RNA testing. Researchers found no relationship between gender and severity of DILI, but individuals with diabetes experienced more severe DILI.


Notes:

This study is an initial analysis of an ongoing prospective study of DILI. Its primary aim is to develop well-characterized cases of medication-related liver injury on which to conduct hypothesis-driven research targeted at developing means to diagnose, prevent and treat DILI. DILI is the most frequent adverse drug-related event leading to abandonment of potentially promising new drug candidates during pre-clinical or clinical development, failure to achieve drug approval, and withdrawal or restriction of prescription drug use after approval.

The Drug-Induced Liver Injury Network is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and was established in 2003 and will operate through 2013. It consists of eight clinical centers, one data coordinating center and NIDDK investigators. Visit
http://dilin.dcri.duke.edu/ to learn more.

About the AGA Institute

The American Gastroenterological Association (AGA) is dedicated to the mission of advancing the science and practice of gastroenterology. Founded in 1897, the AGA is one of the oldest medical-specialty societies in the U.S. Comprised of two non-profit organizations - the AGA and the AGA Institute - our more than 16,000 members include physicians and scientists who research, diagnose and treat disorders of the gastrointestinal tract and liver. The AGA, a 501(c6) organization, administers all membership and public policy activities, while the AGA Institute, a 501(c3) organization, runs the organization's practice, research and educational programs. On a monthly basis, the AGA Institute publishes two highly respected journals, Gastroenterology and Clinical Gastroenterology and Hepatology. The organization's annual meeting is Digestive Disease Week®, which is held each May and is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. For more information, please visit
http://www.gastro.org.

About Gastroenterology

Gastroenterology, the official journal of the AGA Institute, is the most prominent scientific journal in the specialty and is in the top 1 percent of indexed medical journals internationally. The journal publishes clinical and basic science studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. The journal is abstracted and indexed in Biological Abstracts, CABS, Chemical Abstracts, Current Contents, Excerpta Medica, Index Medicus, Nutrition Abstracts and Science Citation Index. For more information, visit
http://www.gastrojournal.org.

Source:
Aimee Frank
American Gastroen>>>Those with acetaminophen liver injury were excluded. <<<< I wonder why they excluded tylenol? Wow, antibiotics? Who would have thought? How terrible that there are any health food stuff that causes liver problems.    

Thanks, very informative. [QUOTE=Bird Girrl] >>>Those with acetaminophen liver injury were excluded. <<<< I wonder why they excluded tylenol? [/QUOTE]

Probably because acitaminophen is the leading cause of liver failure.

So 45% of 13% of liver failures are caused by antibiotics, but they don't say which class of antibiotics. The antibiotics usually implicated in liver failure are Isoniazid and Nitrofurantoin, (neither of which are a tetracycline which are the antibiotics used in AP. Tetracyclines can indeed cause problems with the liver, but this complication is quite rare. Regular testing should be done when on AP).

Other leading causes of liver failure are alcohol, NSAIDS, methotrexate, and vitamin A.

I guess we're all weighing risks when we choose our medical treatments.

Thanks Lynne! Hopefully soon they'll identify which antibiotics are causing this problem.



edited to correct statistics.Gimpy-a-gogo2008-12-01 19:16:23I can believe this.  Levaquin is one that I believe is pretty tough on the liver.  Gentamicin is pretty bad too I think.  So, not only do they kill off all the good bacteria in your gut, but they frag your liver too.  Another great reason to not take an antibiotic unless it's absolutely necessary. [QUOTE=Gimpy-a-gogo] [QUOTE=Bird Girrl] >>>Those with acetaminophen liver injury were excluded. <<<< I wonder why they excluded tylenol? [/QUOTE]

Probably because acitamiophen is the leading cause of liver failure.

So 45% of 13% of liver failures are caused by antibiotcs, but they don't say which class of antibiotics. The antibiotics usually implicated in liver failure are Isoniazid and Nitrofurantoin, (neither of which are a tetracycline which are the antibiotics used in AP. Tetracyclines can indeed cause problems with the liver, but this complication is quite rare. Regular testing should be done when on AP).

Other leading causes of liver failure are alcohol, NSAIDS, methotrexate, and vitamin A.

I guess we're all weighing risks when we choose are medical treatments.

Thanks Lynne! Hopefully soon they'll identify which antibiotics are causing this problem.



edited to correct statistics.[/QUOTE]

A quick trip to the study site reveals the following list of offending antibiotics:

Bactrim (9)
Augmentin (17)
Macrobid (14)
Ketek (5)
Levaquin (5)
Anti-retroviral (9)
Anti TB (12)
Thanks for that info, Jasmine, I was too in a rush to dig up the study...d'oh!

I'm relieved to see none of them are AP antibiotics. (Although I have seen the very rare case of someone going at it with Levaquin---that stuff sounds not too good). Anyway, I really appreciate the info.Ketek is supposed to be really bad on your liver - like 'need a new liver' bad!  I think they only use it when there is no other option now.  I heard that they didn't know it had that side effect, until a cluster of patients who had just been on it showed up on transplant lists.

Augmentin gets used in kids a lot.  Hope the peds say lay off the Tylenol while they are on it!
The numbers, by themselves, are meaningless unless we know how many total people used the drugs in question.  For example, if a million people used augmentin but only 17 suffered liver injury... but only a thousand people used Bactrim and 9 of those suffered liver injury, the augmentin looks pretty good by comparison.  Along the same lines, just because other antibiotics haven't shown up yet in this list doesn't mean they're off the hook.  Perhaps they're not used widely enough to have been "caught" in this study yet.  This study does not appear to be designed to capture the relative risks of various drugs... just to find a good starting point for further research.

Just some thoughts.

So, why do you think they didn't include the aceteminophren (spelling)?

Bob - you said -
 
"Another great reason to not take an antibiotic unless it's absolutely necessary."  You don't consider RA necessary?  ;-)
 
Pip
[QUOTE=Pip!]

So, why do you think they didn't include the aceteminophren (spelling)?

[/QUOTE]

It seems from the study that they are looking for drugs previously unsuspected in widespread liver injury.  Acetaminophen is already a known hepatotoxin.  No need to do a prospective study seeing if it shows up in liver injury cases - we already know it will.
Yeah, but they knew about MTX too but they included it.  Just seemed weird.  I didn't know about Vitamin A tho - tho it makes sense.
 
Pip
ttt Thanks Suzanne...Sometimes I forget what I've already read and posted  [QUOTE=Lynn49]Thanks Suzanne...Sometimes I forget what I've already read and posted 
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