June 2009

Surgical Biopsies to Monitor, Diagnose Serious Liver Diseases Could Be Things of the Past

A new noninvasive blood test could replace surgical biopsies as a way to diagnose and monitor a serious liver condition that can lead to cirrhosis, liver failure and cancer.

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in both adults and children – an estimated 80 million Americans have fatty livers – and encompasses a spectrum of conditions. Among those is nonalcoholic steatohepatitis (NASH). One in four NASH patients will develop cirrhosis, liver failure or liver cancer.

Distinguishing between NASH and its more benign cousin NAFLD has been difficult. There are noninvasive methods like clinical signs, routine laboratory and radiological imaging, and combinations of clinical and blood tests, but their success has been limited. Surgical liver biopsy remains the only reliable way to diagnose NASH and to grade the severity of liver damage.

Ariel Feldstein, MD, of the Institute's Department of Cell Biology and Cleveland Clinic's Department of Pediatric Gastroenterology, led a multicenter research project that identified a new way to diagnose and monitor NASH – a simple noninvasive blood test. The team looked at 139 patients who had NAFLD diagnosed by biopsies from eight medical centers nationwide.

As NASH progresses, a protein called CK-18 is “cleaved,” or essentially cut loose, from inside liver cells and expelled into the patient's bloodstream.

The researchers found that determining the presence of CK-18 in circulating blood is an accurate way to identify patients with NASH – without the need for biopsies and their attendant risks.

“The prevalence of NAFLD is at epidemic proportions, affecting close to 30% of adults and 10% of children in the United States. It's urgent that we develop a simple, reproducible and noninvasive test to accurately distinguish NASH from more benign conditions,” said Dr. Feldstein.

“This also gives us a new tool for frequent monitoring of the disease's progression and to track how well patients respond to therapies,” he said.

Dr. Feldstein's collaborators included A. Rocio Lopez of the Institute's Department of Quantitative Health Sciences, Anna Wieckowska, MD, of the Department of Pediatric Gastroenterology, Nizar N. Zein, MD, of the Department of Gastroenterology and Hepatology, Arthur J. McCullough, MD, Chair of Cleveland Clinic's Department of Gastroenterology and Hepatology; and Yao-Chang Liu, MD, of the Department of Anatomical Pathology at the MetroHealth Medical Center in Cleveland. The research appeared in Hepatology ( http://www3.interscience.wiley.com/journal/106570044/home, ePub May 2009). The research was supported by grants from the Nonalcoholic Steatohepatitis Clinical Research Network and the National Institutes of Health.