Blood Test for Detecting Non-Alcoholic Steatohepatitis

The new test indicates the presence of non-alcoholic steatosis by measuring caspase 3-generated cytokeratin-18 fragments in the blood. The study results were reported in the July 2006 issue of Hepatology.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in both children and adults. While simple steatosis, an accumulation of fat in the liver, is
the usual form and is benign, nonalcoholic steatohepatitis (NASH) can be a very serious condition. As many as 25% of patients progress to cirrhosis and have such complications as liver failure and hepatocellular carcinoma. However, until now, an invasive liver biopsy, which carries a risk of complications, has been the only way to distinguish between the two.

Led by Anna Wieckowska, M.D., of the department of gastroenterology and hepatology at the Cleveland Clinic Foundation (OH, USA), researchers considered a non-invasive way to diagnose NASH and assess histologic severity using a simple blood test. They looked for indicators of liver cell death; specifically, caspase-generated CK-18 fragments that have been shown to label early apoptotic cells.

The researchers tested the blood of 39 patients undergoing liver biopsy for suspected NAFLD and compared the results to the biopsies and also to the blood of 35 healthy age-matched controls. The plasma levels of CK-18 fragments ranged from 105.5-2306.4 u/l and were significantly higher in patients undergoing liver biopsy compared to the healthy controls. The levels were strikingly higher in patients whose liver biopsies resulted in a definite diagnosis of NASH, compared with patients whose liver biopsies showed no NASH or were normal.

Additionally, caspase activity levels independently predicted the presence of NASH. The risk of definitive NASH on liver biopsy grew with increasing plasma levels of caspase 3-generated CK-18 fragments. For every 50 u/l increase in CK-18 levels, the likelihood of having "definitive NASH” increased 86%.

"In summary, our findings suggest that non-invasive monitoring of hepatocyte apoptosis in blood of patients with NAFLD is a reliable tool to differentiate NASH from ‘not NASH' in patients with suspected NAFLD,” the authors reported.

The test showed high sensitivity, specificity, and positive and negative predictive value, leading the authors to suggest it as an important potential clinical tool. "Future
large studies are needed to confirm these observations,” they concluded. Currently, they are planning a large multi-center prospective validation study.



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