Reuters Health Information (2004-11-26): Increased serum caspase activity marks HCV-associated liver damage
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
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.