Antibiotics: Single Largest Class Of Drugs Causing Liver Injury

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Public Health;  Primary Care / General Practice
Article Date: 01 Dec 2008 - 4:00 PDT

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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 Gastroenterological Association