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Serum Apoptotic Caspase Activity As A Marker Of Severity In Hbeag-Negative Chronic Hepatitis B Virus Infection
  1. George V. Papatheodoridis (gpapath{at}cc.uoa.gr)
  1. Hippokration General Hospital of Athens, Greece
    1. Emilia Hadizyannis (emhadzi{at}med.uoa.gr)
    1. Hippokration General Hospital of Athens, Greece
      1. Emmanuel Tsochatzis (mtsochatzis{at}med.uoa.gr)
      1. Hippokration General Hospital of Athens, Greece
        1. Nikolaos Chrysanthos (nchrysanthos{at}yahoo.gr)
        1. Hippokration General Hospital of Athens, Greece
          1. Anastasia Georgiou
          1. Hippokration General Hospital of Athens, Greece
            1. Georgia Kafiri (georgiakafiri{at}hotmail.com)
            1. Hippokration General Hospital of Athens, Greece
              1. Spilios Manolakopoulos (spilios1{at}otenet.gr)
              1. Hippokration General Hospital of Athens, Greece
                1. Dina G. Tiniakos (dtiniak{at}med.uoa.gr)
                1. Laboratory of Histology & Embryology, Medical School, National & Kapodistrian University of Athens, Greece
                  1. Ioannis Giannousis
                  1. 2nd Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital, Greece
                    1. Emmanuel Manesis (emanesis{at}med.uoa.gr)
                    1. Hippokration General Hospital of Athens, Greece
                      1. Athanasios J. Archimandritis (aarchima{at}med.uoa.gr)
                      1. Hippokration General Hospital of Athens, Greece

                        Abstract

                        Background/Aim: In chronic hepatitis C and non-alcoholic fatty liver disease, apoptotic caspases are activated in liver and serum caspase activity has been suggested as a sensitive marker of early liver injury. We investigated whether the serum levels of caspase-generated fragments of cytokeratin-18 are associated with the severity of liver lesions in HBeAg-negative chronic hepatitis B virus (HBV) infection. Patients/Methods: Cytokeratin-18 fragment levels (U/L) were significantly lower in 30 healthy controls (154±31) than in 53 inactive carriers (172±24, P=0.003) than in 62 chronic hepatitis B patients (474±488, P<0.001). Receiver operating characteristic curve showed excellent diagnostic accuracy (c-statistic:0.87) for differentiating inactive carriers from chronic hepatitis B patients. Cytokeratin-18 fragment cut-off level of 240 U/L gave sensitivity of 60% and specificity and positive predictive value of 100% for chronic hepatitis B diagnosis. Cytokeratin-18 fragment levels were also lower in inactive carriers than in 16 chronic hepatitis B patients with transiently normal ALT (327±256, P=0.001) offering good accuracy for such a differentiation (c-statistic:0.78). In chronic hepatitis B patients, serum cytokeratin-18 fragments correlated positively with ALT/AST, viremia, grading score and their immunohistochemical hepatic expression and negatively with platelet counts, but not with fibrosis or steatosis severity. Conclusions: Serum apoptotic caspase activity is strongly associated with presence of liver injury in patients with HBeAg-negative chronic HBV infection. Cytokeratin-18 fragment levels seem to be a very useful marker for differentiation between inactive HBV carrier state and HBeAg-negative chronic hepatitis B, but not for estimation of the severity of liver histological lesions among HBeAg-negative chronic hepatitis B patients.

                        • HBV DNA
                        • caspase
                        • hepatitis B
                        • inactive carriers
                        • liver histology

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