Researchers Have Developed New Way To Identify Liver Side Effects of Medications

According to the findings of a new study, researchers say they have developed a more accurate method of identifying medications that may cause serious liver side effects, revealing a number of drugs that may cause liver toxicity, which were previously viewed as safe.

Researchers from the Perelman School of Medicine at the University of Pennsylvania, led by Dr. Jessie Torgersen, conducted a study to determine which medications are the most toxic to the liver. Instead of basing the determinations on published case reports, which is what is historically done, they used real-world rates of severe acute liver injury.

Liver toxicity, also known as toxic hepatitis or hepatoxicity, is a serious side effect linked to certain medications, which can result in permanent liver damage, scarring of the liver, and, in some cases, liver failure, which can be fatal. Symptoms can include yellowing of the skin and the whites of the eyes, known as jaundice, as well as itching, abdominal pain, fatigue, loss of appetite, nausea, vomiting, rash, fever, weight loss and dark-colored urine.

In findings published in the journal JAMA Internal Medicine on June 24, researchers conducted a series of cohort studies using data from the U.S. Department of Veterans Affairs that included nearly 8 million people without liver or biliary disease at the start of the study. The researchers looked at what happened when the patients in the database began taking one of 194 different medications, which had been linked to four or more reports of hepatoxicity from October 1, 2000 through September 30, 201.

The standard way of determining liver toxicity focuses on reported liver injury cases, which do not consider the size of the population exposed to any given medication. The researchers noted that there was little evidence from real-world data on the incident rates of acute liver injury (ALI) linked to these drugs.

After analyzing the data, the researchers identified 17 drugs linked to high rates of liver injury, including the HIV drug Zerit, the cancer drug Tarceva, the chemotherapy drug Revlimid (also sold as Thalamid), the anti-psychotic drug Thorazine, the antipsychotic drug Compro, the tuberculosis drug Hydra, the immunosuppressant Azasan, the anti-fungals Nizoral and Diflucan, the ACE inhibitor drug Capoten, and the antibiotics Nuvessa, Avalox, Biaxin, Augmentin, Bactrim, Cipro, and Levaquin.

All 17 medications had liver injury rates of five or more hospitalizations per 10,000 person-years. The researchers found that 11 (64%) of those drugs were not previously categorized as having high liver injury risks. Some of the drugs had extremely high rates of liver injury, like Zerit, which was linked to 86 hospitalizations per 10,000 person-years.

The researchers warned that, when factoring in the other drugs that were determined to be toxic to the liver, millions of people worldwide may face an increased risk of acute liver injury.

However, the researchers also indicated that some drugs believed to be dangerous to the liver, such as statins, used to treat high cholesterol, actually had lower rates of liver toxicity than expected. Two other drugs considered toxic to the liver using the old method, the blood pressure drug Atacand and the antibiotic Minocin, had zero hospitalizations per 10,000 person-years, the researchers determined.

Mitigating Liver Toxicity Risks

Researchers indicated it is important to determine liver toxicity rates using real world data, so patients who need the medications can be closely monitored for early signs of liver injury and failure to try to prevent either from occurring. They recommended those patients have more frequent liver-related labs taken to help prevent injury.

“This study provides a framework for investigating postmarketing hepatotoxicity safety signals,” Torgersen’s team concluded. “Future studies should evaluate rates of severe ALI among persons with chronic liver disease to provide evidence on the hepatic safety of medications in these patients.”

The researchers urged doctors to inform patients of the potential risks they face from these drugs and have a conversation about the risks versus the benefits.