Clinical

Increased serum caspase activity marks HCV-associated liver damage

Last Updated: 2004-11-26 12:00:02 -0400 (Reuters Health)

NEW YORK (Reuters Health) - In patients with chronic hepatitis C virus (HCV) infection, detection of apoptotic caspase activation in sera is a sensitive method of detecting early HCV-associated liver, especially in patients with normal aminotransferase levels, researchers in Germany report in the November issue of Hepatology.

Liver damage, caused by alcohol abuse, HCV infection, or other insults, is mediated by hepatocyte apoptosis, which in turn is mediated by intracellular cysteine proteases or caspases, Dr. Klaus Schulze-Osthoff from the University of Dusseldorf noted in comments to Reuters Health.

Having previously shown that these caspases are strongly activated in liver biopsies from HCV-infected patients, the investigators looked for caspase activation in sera from 59 patients with chronic HCV infection and 7 healthy controls.

Using a novel ELISA that detects the liver-specific caspase-cleaved substrate of cytokeratin-18 (CK-18), they were able to show that sera from HCV patients contains "considerably higher" levels of caspase activity than healthy controls.

"While 27% of patients with chronic HCV infection showed normal aminotransferase levels despite inflammatory and fibrotic liver damage, more than 50% of those patients exhibited already elevated serum caspase activity," they report.

Moreover, liver biopsy findings from patients with normal aminotransferase levels showed that elevated caspase activity was significantly associated with stage 2 or higher fibrosis.

"Routine measurement of HCV-related liver damage includes mostly the measurement of liver transaminases in sera," Dr. Schulze-Osthoff said. "However, these surrogate markers detect very late stages of liver damage and approximately 25% to 30% of patients have persistently normal serum transaminases."

These findings, the authors of an editorial write, suggest that identification of CK-18 in blood may help spot patients with aggressive disease despite normal aminotransferases and may provide a valuable tool and legitimate endpoint for assessing anti-HCV therapies.

They also suggest that HCV is an apoptotic liver disease, implying that antiapoptotic therapy may help prevent HCV-related liver disease, Drs. Ariel E. Feldstein and Gregory J. Gores from the Mayo Clinic in Rochester, Minnesota, point out.

Hepatology 2004;40:1044-1045,1078-1087.