2001
DOI: 10.1053/jhep.2001.28229
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Caspase activation correlates with the degree of inflammatory liver injury in chronic hepatitis C virus infection

Abstract: Hepatitis C virus (HCV) infection is a major cause of liver disease characterized by inflammation, cell damage, and fibrotic reactions of hepatocytes. Apoptosis has been implicated in the pathogenesis, although it is unclear whether proteases of the caspase family as the central executioners of apoptosis are involved and how caspase activation contributes to liver injury. In the present study, we measured the activation of effector caspases in liver biopsy specimens of patients with chronic HCV infection. The … Show more

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Cited by 152 publications
(149 citation statements)
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References 57 publications
(67 reference statements)
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“…25 Moreover, immunohistochemistry with novel antibodies specific for the active forms of caspase-3 and -7 revealed that compared with control subjects, caspase activation was considerably elevated in HCV-infected liver tissue. 26 One striking observation in our study was that depending on the grade of inflammatory liver injury, caspase activation was detectable in up to 20% of hepatocytes, although these liver cells mostly displayed neither gross morphological signs of apoptosis nor apoptotic DNA fragmentation as assessed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. This observation suggested that caspase activation might be involved in very early liver damage.…”
Section: H Epatitis C Virus (Hcv) Is Estimated To Infect Upmentioning
confidence: 58%
“…25 Moreover, immunohistochemistry with novel antibodies specific for the active forms of caspase-3 and -7 revealed that compared with control subjects, caspase activation was considerably elevated in HCV-infected liver tissue. 26 One striking observation in our study was that depending on the grade of inflammatory liver injury, caspase activation was detectable in up to 20% of hepatocytes, although these liver cells mostly displayed neither gross morphological signs of apoptosis nor apoptotic DNA fragmentation as assessed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. This observation suggested that caspase activation might be involved in very early liver damage.…”
Section: H Epatitis C Virus (Hcv) Is Estimated To Infect Upmentioning
confidence: 58%
“…5 The percentage of cleaved PARP-positive cells in failing myocardium (about 13%) is considerably higher as reported values obtained by TUNEL assays and other methods based on the detection of fragmented DNA. 5 The comparative evaluation of different methods to monitor apoptosis was addressed previously, 45 and more than 20% cleaved PARP-positive cells but less than 0.5% TUNEL-positive cells were detected in hepatitis C-virus-infected liver tissue using the same antibody. This supported the view that the activation of the caspase cascade is not an irreversible process, indicating cleaved PARP as a marker of early events during the activation of apoptosis.…”
Section: Discussionmentioning
confidence: 99%
“…The antibody was specific for a caspase-generated neoepitope of the p25 fragment of PARP, but did not recognize the full-length protein. 45 After washing in PBS, the secondary Cy3-conjugated goat anti-mouse antibody (Jackson ImmunoResearch Laboratories; 1 : 300) was added to the slides for 30 min. Controls were performed with isotype-matched control antibodies.…”
Section: Immunohistologymentioning
confidence: 99%
“…[3][4][5][6] Previous studies in patients with chronic HCV infection have shown that activation of hepatic caspases closely correlates with inflammation. 7 In addition, detection of caspase-generated CK-18 fragments in sera from patients with chronic hepatitis C virus (HCV) infection has recently been associated with fibrotic liver injury. 8 Another study showed a correlation of CK-18 fragment levels with the proportion of HCV-associated liver steatosis.…”
Section: An Apoptosis Biomarker For Prediction Of Nonalcoholic Steatomentioning
confidence: 99%