Circulating level of large splice variants of tenascin-C is a marker of piecemeal necrosis activity in patients with chronic hepatitis C.
BACKGROUND
It has been reported that histological activity index and piecemeal necrosis are good factors to evaluate the prognosis in patients with chronic hepatitis C (CHC). Thus, there is a need for simple and noninvasive means to assess disease activity and piecemeal necrosis in patients with CHC. In this study, we measured the serum concentrations of large splice variants of tenascin-C (cTN-C) in patients with CHC, and examined their correlation with the degree of inflammatory activity and fibrosis as evaluated in liver biopsy specimens.


METHODS
The serum levels of cTN-C in 150 patients with CHC and 50 healthy volunteers were measured by enzyme-linked immunosorbent. The histology of liver biopsy specimens was also evaluated following the Desmet's grading/staging system and the Ishak's classification. Liver specimens obtained by biopsy were also immunohistochemically evaluated with anti-human tenascin-C antibodies.


RESULTS
Serum cTN-C concentrations were significantly higher in CHC patients than in healthy volunteers (P < 0.0001). The levels of cTN-C showed no significant difference among the fibrosis stages as assessed by the Desmet's grading/staging system and Ishak's classification scores. However, the concentration of cTN-C was significantly correlated with the grade of activity. According to the Ishak's classification, the concentration of cTN-C was increased in proportion to the degree of piecemeal necrosis. Specific immunostaining of cTN-C was observed in limited areas of piecemeal necrosis but not in fibrotic areas.


CONCLUSIONS
The measurement of serum levels of cTN-C is a useful marker of the activity of CHC, in particular of the degree of piecemeal necrosis.
Department of Gastroenterology and Hepatology, Institute of Clinical Medicine and Biomedical Sciences, Mie University Graduate School of Medicine, Japan.
Hideaki
H
Tanaka
Amro
A
El-Karef
Masahiko
M
Kaito
Noriaki
N
Kinoshita
Naoki
N
Fujita
Shinichiro
S
Horiike
Shozo
S
Watanabe
Toshimichi
T
Yoshida
Yukihiko
Y
Adachi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000097:blood / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000097:blood; D012720:Severity of Illness Index; D019063:Tenascin / Q000097:blood*
D015415:Biomarkers; D019063:Tenascin