As other researchers grapple with America’s obesity epidemic and the resulting surge in nonalcoholic fatty liver disease, Dr. Mack Mitchell confronts a much older, more familiar problem. The target? Alcohol-related liver disease, or alcoholic hepatitis, for which few treatment options exist.

Dr. Mitchell, Vice President for Medical Affairs and Professor of Internal Medicine at UT Southwestern, is preparing to lead a national multicenter study comparing potential treatments for alcoholic hepatitis, which can progress to cirrhosis and death. The study, expected to begin this summer, will be conducted at UT Southwestern and seven other sites with $15 million in funding from the National Institutes of Health (NIH).

It will follow a similar but smaller study begun in 2013 that compared the standard corticosteroid treatment to a regimen of two anti-inflammatory agents: the interleukin 1 receptor antagonist anakinra – used to treat rheumatoid arthritis as well as inflammation in newborns – and the phosphodiesterase inhibitor pentoxifylline, combined with the dietary supplement zinc sulfate to improve gut mucosal integrity. Dr. Mitchell says the multidrug regimen improved 90-day survival by about 20 percent compared with the steroid methylprednisolone. However, the number of trial participants was too small to yield statistically significant results, he adds.

Although doctors have known for centuries that too much alcohol can harm the liver, fatty liver disease tied to obesity and insulin resistance is a relatively new medical concept.

The Centers for Disease Control and Prevention (CDC) reports that almost 22,000 Americans died from alcohol-related liver disease in 2016. Dr. Mitchell points out that obesity-related fatty liver disease is difficult to distinguish from alcohol-related fatty liver disease. “Even a skilled liver pathologist can’t look at two liver samples and say, ‘This one was obese and this one drank,’” he notes.

When the damage becomes severe, patients’ livers are unable to remove toxins or help digest food. At that point, the corticosteroid methylprednisolone is standard treatment, says Dr. Mitchell, who is also Chief Medical Officer of Southwestern Health Resources Physician Network.

“For the last 30 years, steroids have been the best thing that we have to offer,” he says. They can stabilize patients while doctors try to convince them to give up alcohol and improve their nutrition – or while a liver transplant is arranged if necessary, Dr. Mitchell says.

However, corticosteroids come with a drawback, he says. They leave users more susceptible to infections. “This side effect is important,” he explains, “because infections are one of the major reasons these people die from their disease. If they get a serious infection on top of liver disease, they often don’t recover, even with antibiotic treatment.”

The new study will compare methylprednisolone to a combination of anakinra and zinc sulfate as well as to the drug granulocyte colony stimulating factor, which stimulates production of stem cells and white blood cells. 

Dr. Mitchell holds the Nancy S. and Jeremy L. Halbreich Professorship in Gastroenterology.