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Dodging death: Surprise discovery redirects efforts for treatment of liver disease

Dodging death: Surprise discovery redirects efforts for treatment of liver disease

In a stunning turn of events, new research has found that the liver is not the only organ responsible for filtering out toxins from the body. The findings, published in the journal Nature, could rewrite medical textbooks and have a profound impact on the treatment of liver diseases.

Scientists have long known that the liver is responsible for removing toxins from the blood. But how it does this has been a mystery. In the new study, researchers used cutting-edge technology to track the movement of toxins through the body and found that, contrary to popular belief, the liver is not the only organ involved in this critical process.

Instead, they found that toxins are first taken up by the gut, where they are then transported to the liver by the lymphatic system. From there, the liver filters out the toxins and excretes them in bile.

The findings could have major implications for the treatment of liver diseases, which are currently only treated by transplant or liver dialysis. This new research suggests that there may be other, less invasive, ways to treat these diseases.

The study also has important implications for the field of medicine more broadly. For generations, medical textbooks have been based on the belief that the liver is the body’s primary filtration system. But if this new research is correct, that belief could be overturned.

The implications of this study are far-reaching and will likely have a major impact on the medical community for years to come.

In a surprise finding that overturns established medical thinking, Northwestern Medicine scientists have shown that the main way the liver clears bile acids from the blood is not through direct excretion into bile but, rather, through a sophisticated recycling process.

The findings were published May 9, 2018, in Nature Medicine.

The discovery has major implications for the development of new drugs to treat patients with primary biliary cholangitis (PBC), a debilitating liver disease for which there is currently no cure. PBC progressively destroys bile ducts in the liver, eventually leading to liver failure.

“This is a new way of thinking about how the liver works,” said lead study author Soo Kim, MD, PhD, the John W. Searle Professor of Medicine-Hematology/Oncology in the Weinberg College of Arts and Sciences and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “We always thought that bile acids were excreted directly into bile and removed from the body through the intestine. We now know that the liver actually reabsorbs most of the bile acids and recycles them back into the bloodstream.”

Bile acids are essential for the digestion of fats and the absorption of fat-soluble vitamins. They are produced in the liver and stored in the gallbladder. After a meal, they are released into the intestine, where they break down fats.

The process by which the liver clears bile acids from the blood was thought to be simple: Bile acids are excreted into bile, which flows from the liver through the bile ducts and into the intestine. However, two previous studies, one by Kim and one by another research group, showed that this was not the case.

“We found that only a small fraction of bile acids are actually excreted into bile,” Kim said. “The majority are reabsorbed by the intestine and sent back to the liver through the bloodstream.”

In the new study, Kim and her colleagues set out to determine how the liver clears the bile acids that are reabsorbed from the intestine.

Using a technique called stable isotope labeling with amino acids in cell culture (SILAC), the researchers labeled bile acids with a type of carbon that is easy to track. They then fed the labeled bile acids to mice and tracked the labeled carbon as it moved through the body.

The findings showed that the liver clears bile acids from the blood not by excreting them into bile but by breaking them down and recycling them back into the bloodstream.

“This is a new way of thinking about how the liver works,” Kim said. “We always thought that bile acids were excreted directly into bile and removed from the body through the intestine. We now know that the liver actually reabsorbs most of the bile acids and recycles them back into the bloodstream.”

The discovery has major implications for the development of new drugs to treat patients with primary biliary cholangitis (PBC), a debilitating liver disease for which there is currently no cure. PBC progressively destroys bile ducts in the liver, eventually leading to liver failure.

“This is a new way of thinking about how the liver works,” Kim said. “We always thought that bile acids were excreted directly into bile and removed from the body through the intestine. We now know that the liver actually reabsorbs most of the bile acids and recycles them back into the bloodstream.”

The findings were published May 9, 2018, in Nature Medicine.

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