Serum caspase activity and liver fibrosis in patients with hepatitis C
Caspase levels are associated with liver injury
Caspase activity in the sera of patients with chronic hepatitis C infection (HCV) may be a more sensitive measure of liver injury than conventional surrogate markers like aminotransferases, according to a new study published in the November 2004 issue of Hepatology. Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD), published by John Wiley & Sons, Inc., is available online via Wiley InterScience.
Liver biopsy is currently the optimal way to determine the actual progression of liver disease, however, it is an invasive procedure with a risk of complications. The current non-invasive method of assessing liver damage involves measuring serum aminotransferase levels. Unfortunately, many patients with HCV infection who have chronic liver damage exhibit persistently normal aminotransferase levels.
In search of a more accurate non-invasive way to assess early liver damage, researchers led by Klaus Schulze-Osthoff and Heike Bantel of the University of Dusseldorf and Hannover Medical School investigated caspase activity levels in the sera of HCV patients, since recent studies have suggested that caspase activation is involved in very early liver damage. Caspases are believed to mediate the key changes surrounding the death of liver cells.
To explore the relationship between sera caspase levels, sera aminotransferase levels, and actual liver damage, the researchers obtained sera from 59 randomly selected patients with chronic HCV infection. They measured aminotransferase levels and found that twenty-seven percent of the patients were in the normal range. The researchers then examined the sera of the 59 patients, as well as that of seven healthy controls, to detect levels of a caspase-generated neopeptide of CK-18.
In the sera of the healthy controls, only low levels of the neopeptide were detectable. "In striking contrast," the authors report, "HCV patients with different grades of disease activity revealed considerably elevated levels of the caspase-generated cleavage fragment." Additionally, more than half of the HCV patients with aminotransferase levels in the normal range had elevated caspase levels.
The researchers then performed liver biopsies on the 16 study participants who had normal aminotransferase levels. They recruited an additional 9 HCV patients with normal aminotransferase levels for statistical accuracy. Comparing the biopsy findings with sera data, they found that elevated caspase levels were significantly associated with higher stages of fibrosis. "Our data imply that compared to detection of aminotransferases, measurement of caspase-mediated CK-18 cleavage in serum might be the more sensitive method to detect higher stages of liver fibrosis in chronic HCV infection," the researchers report.
While longitudinal studies with larger patients cohorts are necessary, say the authors, one might conclude from this study that patients with normal aminotransferase levels but elevated caspase activation more likely have progressive fibrosis and therefore should be monitored carefully.
Amy Molnar | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
Layered 2D material improves efficiency for solar cells and LEDs
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...