Antibiotics: Single Largest Class Of Drugs Causing Liver Injury

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http://www.sciencedaily.com/releases/2008/12/081201081904.htm

Antibiotics: Single Largest Class Of Drugs Causing Liver Injury

ScienceDaily (Dec. 8, 2008) — 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.

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.

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Adapted from materials provided by American Gastroenterological Association, via

EurekAlert!, a service of AAAS.

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