'Do you drink?' Not much, but she got cirrhosis anyway due to a different cause.

"Do you drink?"

The question from her doctor surprised Angela Borei. “I said, ‘Very few and far between.’”

It was a hint of what was to come. The Liberty, South Carolina, woman was eventually diagnosed with cirrhosis, scarring of the liver, and referred to a specialist at MUSC Health. “It scared me when I was diagnosed. The only cirrhosis I’d ever heard of was alcoholic cirrhosis.

That was seven years ago. Since then, Borei, whose cirrhosis was caused by non-alcoholic steatohepatitis, or NASH, is trying to keep it from progressing. So she’s taking part in an international study sponsored by the pharmaceutical company Gilead Sciences, testing whether the drug selonsertib is safe and effective as a treatment for people with NASH and liver scarring. 

Don Rockey, chairman of the Department of Medicine, is leading MUSC’s part of that study. On a recent visit, Borei told him she’d just gone roller skating for the first time in 20 years. “Next Tuesday, we’re going line dancing.”

She feels like she’s getting better, although neither she nor Rockey knows if she’s getting the study medication or a placebo. They’ll find out when the study is over.

That trial is one of many underway at MUSC, which Rockey said is one of just a few research institutions in the United States committing resources in the area of chronic liver disease.

“This is a difficult disease,” Rockey said. “There are really no good medical treatments. We’re trying to make things available for patients who otherwise don’t have options.”

Promising pathway focuses on portal hypertension

Rockey wants to do more than test drugs. He’s trying to figure out new ways to tackle liver disease and its complications. 

So in addition to the multiple clinical trials he’s involved with, he’s leading a national $1.3 million study funded by the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases called “A molecular approach to the pathogenesis of portal hypertension.”  

Portal hypertension, a side effect of cirrhosis, means high blood pressure in a vein that delivers blood from the intestines to the liver for cleaning. It can lead to life-threatening internal bleeding and kidney and lung problems.

In a healthy liver, cells that line the inside of blood vessels release nitric oxide into the body, widening blood vessels and allowing blood to flow smoothly. They’re called endothelial cells.

“What we discovered is that in the injured liver, the enzyme known as endothelial cell nitric oxide, or eNOS, that makes nitric oxide doesn’t work,” Rockey said. “We’re now understanding how that works.” 

Rockey’s team has identified proteins that stick to the enzyme. Some limit its function, some give it a boost. “It turns out in liver injury, the good proteins are down and the bad proteins are up, and your endothelial cells basically don’t work very well. So this whole grant is about endothelial cell biology and eNOS,” Rockey said.

“One of the aims of this grant is to create a novel drug for use in our patients. We’re going to try to figure out how to stimulate the eNOS enzyme/protein and activate it and/or inhibit some of the proteins that hinder the function of ,” Rockey said. “We’re hopeful that we’ll come up with something.”

He said his research team will be pushing hard to get results that can lead to new options. “The translation is the key. We’ve got a specific pathway that we can target.”

Scope of the problem

Over four million adults in the U.S. have some form of liver disease, according to the Centers for Disease Control and Prevention. About 750 South Carolinians died from what the CDC characterizes as “chronic liver disease/cirrhosis” in 2016, the most recent year for which data is available.

The most common causes of cirrhosis: 

• Non-alcoholic fatty liver disease
• Chronic hepatitis C
• Alcohol abuse

Borei, whose NASH was caused by extra fat in her liver, wants to be part of the solution. “It’s hard not knowing whether the selonsertib study is helping me or not. When I was asked to be part of the study, I thought about it for a long time. Then I thought well, you know, even if it doesn’t work for now, maybe they can use it to help somebody in the future.”