The findings could interest the US space agency, which plans to send people to deep space destinations such as an asteroid or Mars by the 2030s -- missions that will require long stays in space.
NASA is already studying the effects of long-term spaceflight on the human body, and recently sent one of its veteran astronauts, Scott Kelly, on a 340-day stay at the orbiting International Space Station, a mission that also included a Russian cosmonaut.
"We knew that astronauts often returned with diabetes-like symptoms but they usually resolved quickly."
The mice spent 13 and a half days aboard the space shuttle Atlantis in 2011.
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Once back on Earth, researchers found that spaceflight appeared to trigger certain cells that may cause scarring and long-term organ damage.
Namely, the mice showed increased fat storage in their livers, as well as a loss of retinol, an animal form of Vitamin A.
Researchers already know that spaceflight can cause a loss of bone and muscle mass, as well as changes in vision and brain function in people.
Jonscher said the signs of liver damage they saw in mice would typically take months to years to develop by eating an unhealthy diet.
"If a mouse is showing nascent signs of fibrosis without a change in diet after 13.5 days, what is happening to the humans?" she asked.
NASA did not immediately respond to a request for comment.
"Whether or not this is a problem is an open question," Jonscher said.
One possibility is that the stress of spaceflight, particularly the jiggling, noise and commotion on departing and re-entering Earth's atmosphere, contributed to the liver damage.