The glasses of wine, the shots of tequila, the blackout nights — those of us who drink can relate to such experiences and more. Other more serious situations are also associated with heavy drinking, including emergency rooms, stomach pumping, and perhaps even liver failure.
Such issues are not exclusively caused by excessive drinking, however. In the United States, there are over 2000 cases of liver failure every year. The near-complete loss of liver function is usually attributed to Tylenol overdosage or hepatitis 1. Patients suffering from acute liver failure either miraculously get better on their own or direly need a liver transplant.
Unfortunately, transplant is frequently the only treatment option. However, researchers from the Hopkins Comprehensive Transplant Center have recently tested certain drugs that mobilize stem cells and could facilitate the regain of liver function.
Andrew Cameron, a surgeon specializing in liver transplantation, has led trials on mice and rats to test the success of using pharmacology instead of transplantation to cure acute liver failure.
“We used carbon tetrachloride to injure the livers,” Cameron said. “It’s been studied fairly well and has been a routinely used toxin for model animals. It damages at the DNA level.” In addition, the researchers also used Tylenol to cause liver damage.
“The humans we see that have liver failure usually attribute it to Tylenol toxicity or hepatitis,” Cameron said. Tylenol toxicity occurs after someone has ingested around 20 grams of Tylenol. According to Cameron, “That’s around 30 tablets.”
The model animals were given enough injurious chemicals so that if they were not treated within a few days, they would have died, thus simulating human acute liver failure.
“Typically the time from severe injury to recovery, death, or transplant is on the order of a week or so,” Cameron said. Once the rodents were sick enough, Cameron and his team began to treat them using a drug called Plerixafor.
“We chose this drug because it had been shown previously to be effective in humans in mobilizing stem cells,” Cameron said.
Plerixafor was originally developed as an anti-HIV drug, believed to affect a co-receptor of HIV. It was found to mobilize stem cells, and now is used for treatments such as blood marrow transplants.
In this trial, Cameron hoped Plerixafor would mobilize stem cells that would regenerate liver function. He believed that Plerixafor affects hematopoietic stem cells, which are identified as CD34.
“The rats’ peripheral CD34 went up, and we saw CD34+ cells in their previously injured livers,” Cameron said.
After being treated with Plerixafor, 80% of the animals survived. The next step, Cameron says, is to test the drug in a large animal model such as a pig.
“If it works in pigs, we’ll put it through clinical trials in humans,” Cameron said. “It’s probably safe to try in humans. We have good confidence that it may work because it is already known to mobilize stem cells in humans.”
Cameron hopes that Plerixafor could provide a safe and effective alternative to liver transplant.
“There just aren’t enough livers to go around,” he said. However, some injuries are too big to recover from. “There may be some people who get to the hospital too late to benefit from any medicine, and in that case, we’d still have to proceed with a liver transplant.”
“Patients with acute liver failure are a difficult group of patients,” Cameron said. “They either get better on their own, they die, or they need a liver transplant.”
He hopes Plerixafor may be the drug that allows patients to get better without a liver transplant. So, for all the Tylenol toxicity, hepatitis, alcohol-caused cirrhosis, and other issues that could lead to acute liver failure, there may be pharmacological hope.
