Newswise — DALLAS – Dec. 18, 2013 – UT Southwestern Medical Center has launched the local arm of a national, multicenter study aimed at finding more effective treatments for alcoholic hepatitis, a disease of the liver that often leads to cirrhosis and death in severe cases.
Alcoholic hepatitis, which inflames and damages the liver, is caused by prolonged, excessive drinking. It is one of three types of alcoholic liver disease, accounting for slightly more than half of U.S. deaths from chronic liver disease and cirrhosis, according to the most recent National Vital Statistics Report from the Centers for Disease Control and Prevention (CDC).
Data from CDC estimates about 5.4 percent of U.S. adults are heavy drinkers, either alcoholics or at high risk for alcoholism. Of that group, about 15 percent will develop serious alcoholic liver damage.
UT Southwestern is among four institutions selected by the National Institutes of Health to share a five-year, $10 million grant comparing new treatments to standard-of-care therapy. Participants will be enrolled in one of two clinical trials, depending on whether their disease stage is moderate or serious.
“Alcoholic hepatitis is one of the most common causes of serious liver disease in the United States,” said Dr. Mack Mitchell, Vice Chairman and Professor of Internal Medicine, who will lead UT Southwestern’s investigation. “If we can develop the right mixture of drugs for optimal treatment, then maybe we finally can prevent progression and improve the outcome of this deadly disease.”
For those with severe disease, researchers will test the effectiveness of a three-drug regimen versus methylprednisolone, an anti-inflammatory corticosteroid given as standard treatment. The drugs to be tested take aim at the disease in three ways: the anti-inflammatory drug anakinra for two weeks to reduce inflammation; the TNF inhibitor drug pentoxifylline for four weeks to counteract an inflammatory response and prevent acute kidney injury; and the mineral zinc sulfate for six months to improve gut permeability.
“The hypothesis is that this is an inflammatory disease that begins because of chronic heavy alcohol consumption,” said Dr. Mitchell, who is in the Division of Digestive and Liver Diseases. “We believe the disease is causing fat to accumulate in liver cells and damaging the lining of the gut in such a way that bacteria get into the bloodstream and cause inflammation in the liver.”
Those with severe disease randomized to the standard-of-care treatment group will receive methylprednisolone for 28 days, a regimen established by an earlier alcoholic hepatitis trial led by Dr. Willis Maddrey, Professor of Internal Medicine and Assistant to the President at UT Southwestern. This earlier multicenter study set the standard of treatment in 1989 for severe cases of acute alcoholic hepatitis.
Those in the moderate disease group will receive either standard-of-care treatment – recommendations to abstain from alcohol and to improve their diets – or the same counseling plus the probiotic lactobacillus rhamnosus GG for six months.
Study participants will be tracked over a three-year period. Mortality rates and improvements in liver function will be measured to compare the various treatments.
Nationally, researchers are seeking 260 trial participants, equally split between the moderate and severe disease groups. In addition, those with early-stage disease can participate in an observational segment of the study that involves a search for disease biomarkers through analysis of blood samples. People interested in taking part in the trial at UT Southwestern can call 214-648-3352 to see if they qualify for this or other liver disease-related trials.
Besides Dr. Mitchell, who handled the FDA application to use the drugs for new investigational purposes, others on the UT Southwestern clinical trial team are Dr. Jennifer Cuthbert, Professor of Internal Medicine, and Dr. Lisa Casey, Assistant Professor of Internal Medicine. Serving on the national trial’s Scientific Advisory Board are Dr. Maddrey, one of the country’s top experts on alcoholic liver disease, who will serve as Chair of the Data Safety Monitoring Board, and Nobel Laureate Dr. Bruce Beutler, Director of the Center for the Genetics of Host Defense at UT Southwestern, whose research on innate immunity laid some of the groundwork for understanding how alcohol injures the liver.
The three other participating trial sites are at the University of Massachusetts, the Cleveland Clinic, and the University of Louisville. Other support for the study, besides the NIH grant, comes from the National Institute on Alcohol Abuse and Alcoholism.
About UT Southwestern Medical CenterUT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty includes many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 91,000 hospitalized patients and oversee more than 2 million outpatient visits a year.
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