WASHINGTON — Digestive Disease Week kicked off on Saturday at the Washington Convention Center, followed by the beginning of presentations of abstracts on Sunday.
DDW organizers of the event call it the "largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.
Among the initial research presentations were studies designed to validate non-invasive methods for evaluating patients with non-alcoholic fatty liver disease (NAFLD).
The current gold standard for detecting liver disease is liver biopsy, which comes with various risks, thus crying out for a non-invasive method of testing. These would include biomarkers that could be used in blood tests for the disease.
During a press conference on Sunday, a group of studies focused on this possibility.
Ariel Feldstein, MD, of the Cleveland Clinic Foundation (Cleveland), presented "Noninvasive Assessment of Hepatocyte Apoptosis in Nonalcoholic Fatty Liver Disease: a Multicenter Validation Study."
The study abstract points out that liver biopsy is the only method currently able to diagnose non-alcoholic steatohepatitis (NASH), the most extreme form of NAFLD, to determine the stage of the disease.
Previous research indicates that a blood test to determine caspase three-generated cytokeratin 18 (CK-18) fragment levels — a non-invasive biomarker test — can predict the incidence and magnitude of NASH.
As an ancillary study of the NASH National Institute of Health Clinical Research Network, 178 patients with biopsy-proven NAFLD participated in the study. Another 150 age-matched health controls were analyzed to validate the biomarker methodology. The team tested the NAFLD patients' blood levels for CK-18 fragments, ranging from 68 U/L to 3000 U/L, which were "significantly higher" than those observed in the 150 healthy controls, who evidenced an average of 45 U/L.
The study indicates that accurately determining CK-18 fragment levels in the blood differentiates NASH from simple steatosis in patients with NAFLD, "supporting the potential of this test in clinical practice as a noninvasive NASH biomarker."
In addition, the study showed that for every 50 U/L increase, the likelihood of having definitive NASH increased by 74%.
In a second study presented Sunday, "Can Phosphoproteomic Analysis of White Adipose Tissue Predict Presence of Insulin Resistance and Resolution of Diabetes Mellitus in Non-Alcoholic Fatty Liver Disease?", researchers looked at connections between white adipose tissue in the abdomen and medical disorders, including insulin resistance and diabetes in patients with obesity and NAFLD. Diabetic patients with NAFLD are among those at risk for progressive liver disease.
The researchers evaluated whether cell signaling pathway profiles within white fat are associated with the presence of insulin resistance and whether they can predict the resolution of diabetes following weight loss.
Conducted at George Mason University (Fairfax, Virginia), the study included 144 patients undergoing bariatric surgery. Before the surgery, 41% of patients had evidence of insulin resistance as measured by a blood test; 25% had diabetes prior to surgery.
During the bariatric surgery, white fat was collected for protein profiling, and the results were analyzed to determine whether the technique could, one, accurately predict insulin resistance in obese individuals, and two, identify which diabetic patients were likely to resolve diabetes following surgery.
When comparing patients with insulin resistance to those without the disorder, the phosphorylation levels of 10 proteins were significantly different in the two groups. When comparing 15 diabetics who resolved their diabetes after weight loss, to 10 who did not, 20 proteins were marked as significantly different between the two groups.
Nearly all of those proteins are associated with insulin signaling, which leads to abnormal blood glucose levels and diabetes. Researchers concluded that prognostic biomarkers can be developed that can potentially predict resolution of complications of obesity such as diabetes.
Zobair Younossi, MD, of Innova Health System's Translational Research Center (Fairfax, Virginia), senior author of the study, during a Q&A, said that in studies such as his, these biomarkers can be used not only for testing but also for treatment, such as when a biomarker is used as a target in drug development for "individualized medicine."
Younossi, however, said that it will be nearly "impossible" to develop tests or drugs based on one protein. Such development, he said, will require a "panel of proteins" that likely act in groups.
He said that researchers should look to multiple pathways to develop panels that will serve to develop "both predictive and prognostic tests" for a wider group of people with NASH.