[Serum hyaluronic acid level: correlation with quantitative measurement of hepatic fibrosis in a cirrhotic rat model].
OBJECTIVE
The serum level of hyaluronic acid (HA) has been suggested as a useful serologic marker for hepatic fibrosis. However, the relationship between serum HA levels and quantitative markers of fibrosis from liver tissue has not been reported. The aim of this study was to determine the correlation between serum HA level and quantitative measurement of hepatic fibrosis in a cirrhotic rat model.


METHODS
Cirrhosis was produced by common bile duct ligation (BDL) in adult Sprague-Dawley rats. The animals were classified into four groups: (1) G1, sham operated (n=5); (2) G2, BDL for 2 weeks (n=6); (3) G3, BDL for 3 weeks (n=6); and (4) G4, BDL for 4 weeks (n=6). Hepatic fibrosis was analyzed histomorphologically using the Batts and Ludwig scoring system. Serum HA level and hepatic hydroxyproline content were quantified. The gene expressions in the liver of procollagen, collagen, and transforming growth factor-beta (TGF-beta) were measured by reverse transcriptase-polymerase chain reaction.


RESULTS
In groups G1, G2, G3, and G4, the Batts and Ludwig scores (mean+/-SD) were 0, 1.3+/-0.5, 2.6+/-0.5, and 3.4+/-0.5, respectively (P<0.05), serum HA levels were 12.5+/-3.2, 30.0+/-4.3, 228.6+/-157.7, and 391.3+/-207.7 ng/mL (P<0.05), and the concentration of hydroxyproline was 12.4+/-2.8, 17.6+/-3.8, 17.9+/-2.4, and 33.4+/-3.4 microg/g liver tissue, and it was significantly higher in group G4 than in the other groups (P<0.05). The gene expressions of collagen, procollagen, and TGF-beta1 in the liver were also significantly higher in group G4 compared with the other groups (P<0.05). Direct linear correlations were observed between serum HA level and hepatic hydroxyproline content, hepatic gene expressions of collagen, procollagen, TGF-beta1, and histomorphological grade of hepatic fibrosis (P<0.001).


CONCLUSIONS
These results indicate that serum HA is a useful and noninvasive serologic marker for the evaluation of advanced hepatic fibrosis.
Kim
Moon Young
MY
Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
Baik
Soon Koo
SK
Jang
Yoon Ok
YO
Suk
Ki Tae
KT
Kim
Jae Woo
JW
Kim
Hyun Soo
HS
Cho
Mi Yun
MY
Choi
Sun Joo
SJ
Um
Soon Ho
SH
Han
Kwang-Hyub
KH
D000818:Animals; D001652:Bile Ducts / Q000473:pathology / Q000601:surgery; D015415:Biomarkers / Q000097:blood; D003094:Collagen / Q000032:analysis / Q000235:genetics; D006820:Hyaluronic Acid / Q000097:blood*; D006909:Hydroxyproline / Q000097:blood; D008026:Ligation; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008297:Male; D023421:Models, Animal; D011347:Procollagen / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018434:Sickness Impact Profile; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics
D015415:Biomarkers; D011347:Procollagen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D006820:Hyaluronic Acid; D003094:Collagen; D006909:Hydroxyproline