Serum apoptotic caspase activity as a marker of severity in HBeAg-negative chronic hepatitis B virus infection.
OBJECTIVE
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. An investigation was carried out into whether the serum levels of caspase-generated fragments of cytokeratin-18 (CK-18) are associated with the severity of liver lesions in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection. Patients/


METHODS
CK-18 fragment serum levels were determined in 115 treatment-naive, consecutive HBV patients and 30 healthy controls. Hepatic-expression of CK-18 fragments was evaluated by immunocytochemistry in chronic hepatitis B patients.


RESULTS
CK-18 fragment levels (U/l) were significantly lower in healthy controls (mean (SD), 154 (31)) than in 53 inactive carriers (172 (24), p = 0.003) and in 62 chronic hepatitis B patients (474 (488), p<0.001). The receiver operating characteristic curve showed excellent diagnostic accuracy (c-statistic: 0.87) for differentiating inactive carriers from chronic hepatitis B patients. A CK-18 fragment cut-off level of 240 U/l gave a sensitivity of 60%, and a specificity and positive predictive value of 100% for chronic hepatitis B diagnosis. CK-18 fragment levels were also lower in inactive carriers than in 16 chronic hepatitis B patients with transiently normal alanine aminotransferase (ALT; 327 (256), p = 0.001), offering good accuracy for such a differentiation (c-statistic: 0.78). In chronic hepatitis B patients, serum CK-18 fragments correlated positively with ALT/aspartate aminotransferase (AST), viraemia, 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 the presence of liver injury in patients with HBeAg-negative chronic HBV infection. CK-18 fragment levels seem to be a very useful marker for differentiation between the 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.
Papatheodoridis
G V
GV
Second Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital of Athens, 114 Vas. Sophias Ave., 115 27 Athens, Greece. gepapath@med.uoa.gr
Hadziyannis
E
E
Tsochatzis
E
E
Chrysanthos
N
N
Georgiou
A
A
Kafiri
G
G
Manolakopoulos
S
S
Tiniakos
D G
DG
Giannousis
I
I
Manesis
E K
EK
Archimandritis
A J
AJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002353:Carrier State / Q000175:diagnosis* / Q000473:pathology; D020169:Caspases / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D015415:Biomarkers; D006513:Hepatitis B e Antigens; D053538:Keratin-18; D000410:Alanine Transaminase; D020169:Caspases