Research conducted at the University of Connecticut on damaged livers has found that people with chronic diseases do not need to stop medication while they heal from drug-induced liver damage.
Xiaobo Zhong, a toxicology professor in the school of pharmacy and José Manautou, department head of pharmaceutical sciences and professor of toxicology, has worked in collaboration with a team of experts to study the effects of liver damage on mice and a liver’s natural ability to regenerate.
“The questions we address are, that if a patient that has developed liver injury by taking an overdose of a medication, like acetaminophen for example, what is the capacity of those individuals to handle medications and metabolize them when they are also undergoing liver recovery?” Manautou said.
Zhong said when a person takes an oral medication, the liver is the first place the medication goes so it can metabolize and release it into the bloodstream. This can lead to liver damage, especially if you have a chronic illness such as diabetes.
“We went to the UConn Health and they have a poison control center there, and when patients indicate liver damage, clinicians told us when they see these patients the first idea is to stop all medications a patient may be on,” Zhong said.
There is no standard time it may take a liver to heal after stopping the medication, and conditions for those with chronic illnesses can suffer as a cost, Zhong said.
“The work that we did in collaboration with Zhong’s lab was to understand if a liver that has been injured has the capacity to handle and metabolize pharmaceuticals that are used to treat patients with things like diabetes and psychological conditions,” Manautou said.
Acetaminophen, the active ingredient in Tylenol, was used as a model compound to induce liver injury in mice, Manautou said.
“We wanted to see how the injury affects the capacity of the liver to metabolize any medications that a patient could be taking on a chronic basis,” Manautou said.
The liver is the only organ that can regenerate itself when it is injured, Manautou said.
“We are finding that based on the reduced ability to metabolize medications, that one of the recommendations wouldn’t be to discontinue the medications but to reduce the medication doses because the liver has a reduced capacity to metabolize those medications,” Manautou said.
Manautou said people on medication have often been prescribed a dosage that falls within a safe range of doses that a person can take, called a therapeutic window.
“You have a therapeutic window for medical treatment, that allows some room for medication doses, if you go above the therapeutic doses you risk averse effects of those medications, if you go below that dose then the medication will no longer [be] effective for treating that condition,” Manautou said. “Patients are usually given the middle dose in that therapeutic window so that it can be increased or decreased based on how the patient is responding to the therapy.”
Zhong and Manautou have met with clinicians at UConn Health in anticipation of working to further their research with human patients who have a liver injury.
“We first need to demonstrate these findings with our animals before we move on to humans and it’s something we are working to collaborate with UConn Health on,” Zhong said.
Learning more about that therapeutic window is important in the next steps of their study, Manautou said.
“We want to know what is the actual window we are dealing with when the tissue heals and recovers, does the liver recover the capacity to handle medications in the same time frame,” Manautou said.
Zhong said they want to do an extended time study to track the course of recovery from liver injury in humans.
“This is important if we see the same in mice that we also see in humans, and can change the way patients are treated for liver injury,” Zhong said.
Manautou said they hope to get clinically relevant studies on the work he and Zhong have done with mice and see how long the effects of an injured liver might last.
“This research should show an improved therapeutic managed care with patients because right now the decision to discontinue medications is based on a practice that makes sense but isn’t an evidence-based decision,” Manautou said. “We are proposing that our work will provide that evidence on how to better treat patients that are ongoing liver injury and how to better manage the existing conditions.”
Thumbnail photo courtesy of Zhong Research Lab website.
Naiela Suleiman is a campus correspondent for The Daily Campus. She can be reached via email at firstname.lastname@example.org.