Premium
Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury
Author(s) -
Bantel Heike,
Lügering Andreas,
Heidemann Jan,
Volkmann Xandra,
Poremba Christopher,
Strassburg Christian P.,
Manns Michael Peter,
SchulzeOsthoff Klaus
Publication year - 2004
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20411
Subject(s) - cirrhosis , hepatocellular carcinoma , fibrosis , medicine , liver injury , hepatitis c virus , apoptosis , caspase 3 , caspase , hepatitis c , pathology , immunology , biology , virus , programmed cell death , biochemistry
Chronic hepatitis C virus (HCV) infection is characterized by inflammatory liver damage and is associated with a high risk of development of cirrhosis and hepatocellular carcinoma. Although histological examination of liver biopsies is currently the gold standard for the detection of early liver damage, there is a strong need for better noninvasive methods. We recently demonstrated that the proapoptotic activation of caspases is considerably enhanced in histological sections from HCV‐infected liver tissue, suggesting an important role of apoptosis in liver damage. Here, we investigated whether caspase activation is detectable also in sera from patients with chronic HCV infection. Using a novel enzyme‐linked immunosorbent assay that selectively recognizes a proteolytic neoepitope of the caspase substrate cytokeratin‐18, we demonstrate that caspase activity is markedly increased in the sera of HCV patients. Interestingly, 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. Moreover, 30% of patients with normal aminotransferase but elevated caspase activity revealed higher stages of fibrosis. In conclusion , compared with conventional surrogate markers such as aminotransferases, detection of caspase activity in serum might be a more sensitive method of detecting early liver injury. Thus, measurement of caspase activity might provide a novel diagnostic tool, especially for patients with normal aminotransferases but otherwise undiagnosed histologically active hepatitis and progressive fibrosis. (H EPATOLOGY 2004;40:1078–1087.)