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June 15, 2017

An inside peek at the weird, wondrous human liver

Daily Briefing

The human liver is the largest organ in the body, and next to the brain it performs the most distinct functions—and it is one of the few organs that cannot be replaced or replicated by a machine, Natalie Angier writes for the New York Times.

"We have mechanical ventilators to breathe for you if your lungs fail, dialysis machines if your kidneys fail, and the heart is mostly just a pump, so we have an artificial heart. ... But if your liver fails, there's no machine to replace all its different functions, and the best you can hope for is a transplant," Anna Lok, president of the American Association for the Study of Liver Diseases and director of clinical hepatology at the University of Michigan, said.

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But scientists are hopeful that recent findings about the liver will spur new therapies for the over 100 disorders that can affect the organ.

The powers of the liver

The powers of the liver are " profound," Angier writes, explaining that the liver is the only organ in the adult body that after being "chopped down" can "rapidly regenerate and perform as if brand-new."

The liver performs more than 300 tasks—second in number only to the brain, according to Angier. Those tasks include, but are not limited to, neutralizing potentially harmful substances we put in our bodies, regulating blood chemistry, generating hormones and enzymes, and converting food into "building blocks" for cells. And the more scientists research the liver, "the longer the liver's inventory of talents and tasks becomes," Angier writes.

For instance, one recent study of mice found that the liver grows and shrinks up to 40 percent over the course of 24 hours—a characteristic that isn't shared by surrounding organs.

In addition, scientists have found that the metabolically active cells that make up 80 percent of the liver, hepatocytes, have traits unseen in any other normal cells in the body, Angier writes. Hepatocytes can have up to eight sets of chromosomes without becoming cancerous or coming apart, while most cells have only two sets. Markus Grompe, who studies the phenomenon at Oregon Health and Science University, called the phenomenon "superunique," saying it likely in part explains the liver's regenerative ability.

Grompe and other researchers have shown that the cells' ability to handle multiple sets of chromosomes makes them like immune cells: "genetically diverse enough to handle nearly any poison thrown at them."

The liver also may play a prominent role in appetite and food preference, according to research published last month. Researchers recently demonstrated that after exposure of a sugary drink, the liver seeks to curb further sugar indulgence by releasing a hormone called fibroblast growth factor 21 (FGF21). The researchers found mutant version of FGF21 was associated with a sweet tooth.

Why is the liver so strange?

According to Angier, "Many of the liver's unusual features are linked to its intimate association with blood." It's where blood cells come from during fetal development, for instance.

Tactics to attract and retain transplant patients

As Markus Heim, a liver researcher at the University of Basel put it, "Hepatocytes are swimming with blood." He explained, "That's what makes them so incredibly efficient at taking up substances from the blood." Angier writes that the liver's function as "the master sampler of circulating blood" keeps the organ on top of the body's energy demands.

Future studies needed

But many unanswered questions remain, Angier writes. For instance, researchers have yet to discover why the liver oscillates in size. But Angier reports that researchers hope a new wave of research will provide much-needed insight into the organ and identify new ways to treat the more than 100 disorders that can afflict the liver.

As Valerie Gouon-Evans, a liver specialist at the Mount Sinai School of Medicine, put it, "The liver is not a very sexy organ. It doesn't look important. It just looks like a big blob," adding, "But it is quietly vital, the control tower of the body" (Angier, New York Times, 6/12).

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