title: Caspase-cleaved fragments of cytokeratin-18 as a marker of inflammatory activity in chronic hepatitis B virus infection.
abstract: BACKGROUND
  The differential diagnosis between inactive carrier and active hepatitis is important in patients with chronic hepatitis B (CHB) virus infection. Serum cytokeratin (CK)-18 fragments (M30-antigen) are proposed as biomarkers of apoptosis.
  
  
  OBJECTIVE
  We investigated whether serum M30-antigen levels might help to characterize the various phases of CHB and predict the state of significant inflammation in patients with CHB.
  
  
  METHODS
  A total of 339 CHB patients who underwent liver biopsy, were included. Serum M30-antigen levels were compared between inactive carriers (n=21), patients with HBeAg-negative hepatitis (n=95), HBeAg-positive hepatitis (n=141) and liver cirrhosis (n=82).
  
  
  RESULTS
  Serum M30-antigen levels were correlated significantly not only with AST (r=0.544, p<0.001) and ALT (r=0.315, p<0.001) and but also inflammatory grading score on liver biopsy (r=0.240, p<0.001). Serum M30-antigen level in HBeAg-negative CHB was significantly higher than that of inactive HBV carrier (399.78 U/L vs 148.90 U/L, p<0.001). Multivariate analysis showed that AST (p<0.001), albumin (p=0.009) and M30-antigen (p=0.020) were the independent predictors of significant inflammation. Combined serum M30-antigen level (>344 U/L) and AST (>78 IU/L) measurement provided the most accurate identification of significant inflammation, showing 38.2% sensitivity, 96.1% specificity, 91.0% positive predictive value and 56.1% negative predictive value.
  
  
  CONCLUSIONS
  Serum M30-antigen can be a predictive marker for distinguishing between inactive carrier and HBeAg-negative CHB. Serum M30 levels are associated with the presence of significant inflammation, especially in patients with normal or minimally elevated ALT in CHB patients.
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Chang Bum
authors.initials: CB
authors.lastname: Bae
authors.forename: Soon Sun
authors.initials: SS
authors.lastname: Kim
authors.forename: Seun Joo
authors.initials: SJ
authors.lastname: Ahn
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Cho
authors.forename: Sei Rhan
authors.initials: SR
authors.lastname: Kim
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.forename: Ga Won
authors.initials: GW
authors.lastname: Song
authors.forename: Dong Joon
authors.initials: DJ
authors.lastname: Kim
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Hwang
authors.forename: Jin Mo
authors.initials: JM
authors.lastname: Yang
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Kim
authors.forename: Young Nyun
authors.initials: YN
authors.lastname: Park
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cheong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D007249:Inflammation / Q000097:blood; D053538:Keratin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D012372:ROC Curve; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053538:Keratin-18; C561463:M30 cytokeratin-18 peptide, human; D010446:Peptide Fragments; D001219:Aspartate Aminotransferases
keywords: Apoptosis; Chronic hepatitis B; Cytokeratin-18; Inactive carrier; Significant inflammation