Filtering out the mystery surrounding liver damage
The liver is the body’s natural filter, removing toxins from the bloodstream by chemically neutralizing them. Because of this role, the liver is vulnerable to damage from substances that most people don’t think of as poisonous, such as prescription medications, herbal supplements and over-the-counter drugs.
Such adverse reactions, though rare, are the No. 1 cause of acute liver failure, a serious illness that can result in the need for a liver transplant or even death. They’re also the leading reason why potentially life-saving medications are pulled from the market after they’re approved -- or never make it to market.
“Severe liver injury has a very high mortality rate,” says Dr. Leonard B. Seeff, a liver expert at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md. “But aside from the obvious risk factors like drinking too much alcohol or viruses, which weaken the liver, we can’t predict who is going to develop liver damage from taking drugs.”
Scientists hope to soon find out.
In an effort to develop better ways to detect, prevent and treat this problem, the institute has established the Drug-Induced Liver Injury Network, composed of six university research centers across the country.
The network’s first two studies will focus on patients who suffered severe liver injuries that were triggered by prescription drugs, over-the-counter medications or dietary supplements. Scientists suspect that the injuries were caused by a complex interplay between genetic and environmental factors, but they hope this research will identify the specific causes. If so, medications could become safer for everyone.
“We’re trying to understand why two perfectly healthy people can be taking the same drug, and one suddenly turns yellow and dies,” says Dr. Paul B. Watkins, a liver expert at the University of North Carolina at Chapel Hill and chairman of the liver network’s steering committee. “What provokes these sudden, out-of-the-blue catastrophic events?”
One study involves people older than 2 who recently suffered liver damage after taking any drug or herbal medicine. These patients will be followed over time to find out what happened to them as a result of their injury. Other people who took the drugs but didn’t sustain liver damage will also be enrolled. All study participants will give blood and urine samples for diagnostic and genetic analysis; they’ll also have an ultrasound scan of their liver, and complete health questionnaires that include family histories.
The other study is looking at people who have suffered liver damage in the last 10 years due to four widely prescribed medications that are known to harm the liver. These drugs are the anti-tuberculosis medication isoniazid; phenytoin (Dilantin), which is used to control seizures; the popular antibiotic amoxicillin; and a migraine and epilepsy drug, valproic acid (Depakote).
A minimum of 50 cases of each form of drug-induced liver toxicity will be collected along with an equal number of patients who have taken the drugs safely. These volunteers will have blood drawn, be interviewed about their experience with the drug, and have their medical records reviewed. The data will then be entered into a drug registry.
Researchers hope the studies will answer such key questions as the actual frequency of these adverse reactions; the mechanisms that trigger the toxicity; and the genetic signature of people who are more susceptible.
“Our goal is to provide useful information for physicians and patients regarding risks of otherwise safe medications,” says Dr. Robert Fontana, a liver specialist at the University of Michigan in Ann Arbor and co-leader of the national trial, “and how to distinguish between benign reactions that are not going to lead to injury and the ones that will.”
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The dangers of acetaminophen
More than half of all cases of acute liver failure are caused by overdoses of acetaminophen, which accounts for more than 56,000 emergency room visits, 2,600 hospitalizations and an estimated 458 deaths each year.
Acetaminophen is the active ingredient in popular over-thecounter drugs such as Tylenol. Most people who overdose on the drug do so unintentionally by ingesting too much of it over the course of several days, says Dr. William M. Lee of the University of Texas Southwestern Medical Center at Dallas. He’s the principal investigator at the Acute Liver Failure Group, which is funded by the National Institutes of Health.
“People take these pills like they’re M&Ms;, but they need to be careful,” Lee says. “There is this halo of safety around Tylenol that is not warranted.”
The standard recommended dose for acetaminophen is 1,000 milligrams four times a day, or 4 grams a day. It’s easy to exceed that -- people may end up in the emergency room after taking 6 to 8 grams for three days.
