Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis.
OBJECTIVE
To investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis in patients with nonalcoholic fatty liver disease (NAFLD).


METHODS
A total of 83 patients with suspected NAFLD and 49 healthy volunteers were investigated. Patients with suspected NAFLD were classified according to their liver histology into four groups: definitive NASH (n=45), borderline NASH (n=24), simple fatty liver (n=9), and normal tissue (n=5). Serum levels of caspase-3 generated cytokeratin-18 fragments (M30-antigen) and total cytokeratin-18 (M65-antigen) were determined by ELISA.


RESULTS
Levels of M30-antigen and M65-antigen were significantly higher in patients with definitive NASH compared to the other groups. An abnormal value (> 121.60 IU/L) of M30-antigen yielded a 60.0% sensitivity and a 97.4% specificity for the diagnosis of NASH. Sensitivity and specificity of an abnormal M65-antigen level (> 243.82 IU/L) for the diagnosis of NASH were 68.9% and 81.6%, respectively. Among patients with NAFLD, M30-antigen and M65-antigen levels distinguished between advanced fibrosis and early-stage fibrosis with a sensitivity of 64.7% and 70.6%, and a specificity of 77.3% and 71.2%, respectively.


CONCLUSIONS
Serum levels of M30-antigen and M65-antigen may be of clinical usefulness to identify patients with NASH. Further studies are mandatory to better assess the role of these apoptonecrotic biomarkers in NAFLD pathophysiology.
Yilmaz
Yusuf
Y
Uludag University Medical School, Department of Internal Medicine, Bursa 16059, Turkey. yusufyilmaz@uludag.edu.tr
Dolar
Enver
E
Ulukaya
Engin
E
Akgoz
Semra
S
Keskin
Murat
M
Kiyici
Murat
M
Aker
Sibel
S
Yilmaztepe
Arzu
A
Gurel
Selim
S
Gulten
Macit
M
Nak
Selim-Giray
SG
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003937:Diagnosis, Differential; D005234:Fatty Liver / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006505:Hepatitis / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D000637:Transaminases / Q000097:blood; D014463:Ultrasonography
D015415:Biomarkers; D053538:Keratin-18; D000637:Transaminases