Circulating matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 as serum markers of fibrosis in patients with chronic hepatitis C - Relationship to interferon response

被引:99
作者
Kasahara, A
Hayashi, N
Mochizuki, K
Oshita, M
Katayama, K
Kato, M
Masuzawa, M
Yoshihara, H
Naito, M
Miyamoto, T
Inoue, A
Asai, A
Hijioka, T
Fusamoto, H
Kamada, T
机构
[1] OSAKA UNIV,SCH MED,DEPT MED 1,SUITA,OSAKA 565,JAPAN
[2] OSAKA NATL HOSP,DEPT GASTROENTEROL,OSAKA,JAPAN
[3] OSAKA ROUSAI HOSP,DEPT MED,OSAKA,JAPAN
[4] OSAKA KOUSEI NENKIN HOSP,DEPT MED,OSAKA,JAPAN
[5] OSAKA PREFECTURE HOSP,DEPT GASTROENTEROL & METAB,OSAKA,JAPAN
[6] CTR ADULT DIS,DEPT GASTROENTEROL,OSAKA 537,JAPAN
[7] OSAKA POLICE HOSP,DEPT MED,OSAKA,JAPAN
[8] NATL OSAKA S HOSP,DEPT GASTROENTEROL,OSAKA,JAPAN
关键词
chronic hepatitis C; interferon; liver fibrosis; matrix metalloproteinase; tissue inhibitor of matrix metalloproteinase;
D O I
10.1016/S0168-8278(97)80423-0
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims/Methods: The imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is considered to be an important determinant of extracellular matrix deposition and breakdown, We measured serum MMP-1, MMP-2, TIMP-1 and TIMP-2 levels using the respective one-step sandwich enzyme immunoassays in 98 patients with chronic hepatitis C treated with interferon beta to examine their clinical significance for assessment of liver histology and to determine whether they can be useful as predictors of the interferon response. Results: Serum TIMP-1 levels showed a positive correlation with the degree of fibrosis (r(s)=0.30, p=0.004). Serum MMP-2 levels revealed positive relationships with the degree of periportal necrosis (r(s)=0.32, p=0.002), the degree of fibrosis (r(s)=0.26, p=0.01) and total score of histological activity index (r(s)=0.24, p=0.02). Serum MMP-2 levels were significantly higher in patients with no response than in those with sustained and transient response (p<0.01 and p<0.05, respectively), while serum MMP-1 levels did not differ among the three groups, Compared with the levels in sustained responders, the total amounts of serum TIMP-1 were significantly lower in transient responders and non-responders (p<0.01 and p<0.001, respectively). As for serum TIMP-2 levels, a significant decrease was found in transient responders and non-responders (p<0.01). The ratios of serum MMP-2 to TIMP-1 levels were significantly higher in transient responders and non-responders than in sustained responders (p<0.001, respectively) even when HCV RNA levels were low in patients with HCV genome subtype Ib or when the HCV genome subtype was 2a or 2b. Sustained response was never found in type Ib patients with ratios of serum MMP-2 to TIMP-1 levels of over 6.0, In logistic multivariate regression analysis, the ratios of serum MMP-2 to TIMP-1 level (p=0.0001), HCV genome subtype (p=0.005) and serum TIMP-2 level (p=0.03) were the independent predictors for sustained response, while serum MMP2 level (p=0.0006) was the only predictor for no response. Conclusions: Serum MMP-2 and TIMP-1 levels might be useful for estimating the degree of liver fibrosis, The ratio of serum MMP-2 to TIMP-1 levels may serve as a new predictor of interferon response in patients with chronic hepatitis C.
引用
收藏
页码:574 / 583
页数:10
相关论文
共 54 条
[1]   MATRIX DEGRADATION IN THE LIVER [J].
ARTHUR, MJP .
SEMINARS IN LIVER DISEASE, 1990, 10 (01) :47-55
[2]   Expression of tissue inhibitor of metalloproteinases 1 and 2 is increased in fibrotic human liver [J].
Benyon, RC ;
Iredale, JP ;
Goddard, S ;
Winwood, PJ ;
Arthur, MJP .
GASTROENTEROLOGY, 1996, 110 (03) :821-831
[3]  
CARTER EA, 1982, GASTROENTEROLOGY, V82, P526
[4]   THE INTERACTION OF PURIFIED RABBIT BONE COLLAGENASE WITH PURIFIED RABBIT BONE METALLOPROTEINASE INHIBITOR [J].
CAWSTON, TE ;
MURPHY, G ;
MERCER, E ;
GALLOWAY, WA ;
HAZLEMAN, BL ;
REYNOLDS, JJ .
BIOCHEMICAL JOURNAL, 1983, 211 (02) :313-318
[5]   TREATMENT OF CHRONIC HEPATITIS-C WITH RECOMBINANT INTERFERON-ALFA - A MULTICENTER RANDOMIZED, CONTROLLED TRIAL [J].
DAVIS, GL ;
BALART, LA ;
SCHIFF, ER ;
LINDSAY, K ;
BODENHEIMER, HC ;
PERRILLO, RP ;
CAREY, W ;
JACOBSON, IM ;
PAYNE, J ;
DIENSTAG, JL ;
VANTHIEL, DH ;
TAMBURRO, C ;
LEFKOWITCH, J ;
ALBRECHT, J ;
MESCHIEVITZ, C ;
ORTEGO, TJ ;
GIBAS, A .
NEW ENGLAND JOURNAL OF MEDICINE, 1989, 321 (22) :1501-1506
[6]   RECOMBINANT INTERFERON-ALFA THERAPY FOR CHRONIC HEPATITIS-C - A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL [J].
DIBISCEGLIE, AM ;
MARTIN, P ;
KASSIANIDES, C ;
LISKERMELMAN, M ;
MURRAY, L ;
WAGGONER, J ;
GOODMAN, Z ;
BANKS, SM ;
HOOFNAGLE, JH .
NEW ENGLAND JOURNAL OF MEDICINE, 1989, 321 (22) :1506-1510
[7]  
DIXON WJ, 1985, BMDP STATISTICAL SOF
[8]   ACTIVE AND LATENT COLLAGENASE ACTIVITY DURING REVERSAL OF HEPATIC-FIBROSIS IN MURINE SCHISTOSOMIASIS [J].
EMONARD, H ;
GRIMAUD, JA .
HEPATOLOGY, 1989, 10 (01) :77-83
[9]   CELLULAR SOURCES OF COLLAGEN AND REGULATION OF COLLAGEN PRODUCTION IN LIVER [J].
FRIEDMAN, SL .
SEMINARS IN LIVER DISEASE, 1990, 10 (01) :20-29
[10]   A ONE-STEP SANDWICH ENZYME-IMMUNOASSAY FOR TISSUE INHIBITOR OF METALLOPROTEINASES-2 USING MONOCLONAL-ANTIBODIES [J].
FUJIMOTO, N ;
ZHANG, J ;
IWATA, K ;
SHINYA, T ;
OKADA, Y ;
HAYAKAWA, T .
CLINICA CHIMICA ACTA, 1993, 220 (01) :31-45