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Developing a tool to help doctors treat chronic liver disease early

Almost 5 million American adults have been diagnosed with liver disease

Dr. Schreiner
Dr. Andrew Schreiner says early detection of liver disease can save lives. Photo by Sarah Pack
Kimberly McGhee | mcgheek@musc.edu | October 23, 2018

MUSC Health primary care physician Andrew D. Schreiner, M.D., was recently awarded a five-year $865,000 grant from the National Institute of Diabetes and Digestive and Kidney Diseases to develop a clinical decision tool to help primary care physicians recognize and treat chronic liver disease in its early stages, when interventions are most effective. Primary care physicians often see abnormal liver function tests for patients but rarely intervene because little evidence currently connects these results to the development of specific chronic liver diseases. 

“Due to the lack of current evidence, we don’t act upon them in a standardized or aggressive ways in primary care,” said Schreiner. “And sometimes those abnormal liver tests are early clinical signals of underlying liver disease that may be problematic in the future.”
 
Chronic liver disease is now the twelfth leading cause of death in the U.S., according to the Centers for Disease Control and Prevention. Unlike cardiovascular disease, which takes the number one spot but has seen a decrease in death rates due to anti-smoking and other measures, the rate of chronic liver disease is on the rise. For example, non-alcoholic fatty liver disease, now affects 30 percent of people in developed countries, making it the most common cause of chronic liver disease in the Western world. 
 
Too often, patients learn they have chronic liver disease only after it has become very advanced and treatment options are limited. Earlier identification of disease could lead to earlier treatment and better outcomes. For instance, patients with hepatitis C could be treated with newly available, effective medication that can rid them of the virus. Patients with nonalcoholic fatty liver disease could be counseled on diet and weight loss and advised to begin statins.  
 
Schreiner is supported by a team of superb and committed mentors, including primary mentor Don C. Rockey, M.D., William P. Moran, M.D., Patrick D. Mauldin, Ph.D., and Valerie Durkalski-Mauldin, Ph.D. With ongoing mentorship and funding from the grant, Schreiner will review the records of 11,000 primary care patients with abnormal liver function tests and track which of those patients went on to develop a chronic liver disease.
 
Although “normal” liver function tests may be similar, abnormal ones vary widely, and that variation could be useful in predicting which chronic liver disease a person is likely to develop, if any. An experienced team of bioinformaticists will look for correlations between given “phenotypes” of results and specific chronic liver diseases and will use those, along with clinical variables and demographic information available in the electronic health record, to develop predictive analytics. In other words, if a connection between a given phenotype of abnormal result and a given chronic liver disease can be established, then new patients presenting with that phenotype would be considered at high risk of developing the corresponding disease. 
 
The team of bioinformaticists includes Mauldin, Durkalski-Mauldin, Jingwen Zhang, M.S., and  John Bian, Ph.D., who have successfully created predictive models for kidney transplant. They will use a form of artificial intelligence known as deep learning to find the correlations between test result phenotypes and specific chronic liver diseases. They will then design a decision support tool that would reside on the electronic health record and provide treatment recommendations to physicians that are tailored to each patient’s specific liver function test results. 
 
If the team is successful in developing a decision support tool during the grant funding period, the next step will be to test it in a large primary care practice. “We think by early identification and potentially early treatment we will have the opportunity to reduce liver disease-related mortality and all-cause mortality,” said Schreiner. “We will have the ability to reduce liver transplantations. Primary care physicians will be in a position to improve a lot of really important health outcomes related to liver disease.” 
 
But these potential benefits could not be realized without the grant funding. Schreiner credits an external review by a top expert in the field funded by the South Carolina Clinical and Translational Research Institute as instrumental in the successful grant application.
 
“SCTR funded a world-class reviewer who was able to review the grant and provide fabulous critical feedback that allowed us to tweak some pretty major components and create a far better product and we would not have been able to do that without SCTR’s help,” said Schreiner.

MUSC is studying chronic liver disease in multiple trials (MUSC Catalyst News, April 19, 2018)

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