Clinical

Caspase activity a useful marker of liver injury in chronic hepatitis B

Last Updated: 2008-04-17 16:17:35 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Serum apoptotic caspase activity is strongly associated with the presence of active liver histological lesions in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B infection, according to a recent study by Greek researchers.

The level of serum apoptotic caspase activity is also valuable, they found, for differentiating between inactive chronic HBV carriers and patients with HBeAg-negative chronic hepatitis B (CHB).

Published in the April issue of Gut, the study is reportedly the first to systematically evaluate the significance of serum apoptotic caspase activity in patients with HBeAg-negative chronic hepatitis B.

Hepatocyte apoptosis triggered by liver injury activates several cysteine-aspartate proteases, also known as caspases, which are known to cleave the cellular protein cytokeratin-18 (CK-18), the researchers explain. The study methodology used a novel ELISA that measures serum levels of CK-18 fragments, as markers for serum apoptotic caspase activity.

For the study, Dr. G. V. Papatheodoridis of the Athens University Medical School and colleagues recruited 115 consecutive treatment-naive HBV patients and 30 healthy volunteer healthcare workers as controls.

Mean CK-18 fragment levels were lowest in the healthy controls, higher in inactive HBV carriers and highest in HBeAg-negative CHB patients.

Because HBeAg-negative CHB patients with transiently normal ALT activity can easily be misclassified as inactive HBV carriers, the researchers assessed CK-18 fragment levels in this subgroup. In the 16 CHB patients with normal ALT on the day of measurement, CK-18 fragment levels were significantly higher than in inactive carriers (p = 0.001) and relatively lower than in the 46 CHB patients with increased ALT (p = 0.077).

When CK-18 levels were quantitatively assessed in the 62 CHB patients, they correlated significantly with not only ALT but also several other relevant measures, such as serum HBV DNA (p = 0.026). Overall, however, CK-18 levels did not correlate with severity of histological lesions.

The team concludes that "these data certainly deserve further evaluation and validation in larger, prospectively followed cohorts.

Gut 2008;57:500-506.