Matrix metalloproteinase-1, tissue inhibitor of matrix metalloproteinase-1 and caspase-3 in Egyptian patients with hepatitis c virus infection with and without schistosomal hepatic fibrosis

Abstract EN

-Background: Hepatic schistosomiasis is a chronic parasitic disease endemic in rural areas in Egypt.

Hepatitis C viral infection represents a viral pandemic.

Chronic liver diseases are accompanied by changes in the pathways regulating apoptosis and extracellular matrix deposition.

Aim: The aim of the current work was to evaluate the levels of serum Matrix Metalloproteinase-1 (MMP-1),Tissue Inhibitor of Matrix Metalloproteinase-1 (TIMP-1) and Caspase 3 in patients with pure hepatitis C infection, mixed hepatitis C infection and hepatic schistosomiasis, and pure hepatic schistosomiasis.

Subjects and methods: Eighty two subjects were included in the present study.

They were divided into Control group(groupI) (twenty five apparently healthy volunteers ) and Patients group(group II)(fifty seven patients).The patients group was further subdivided into :GroupIIa( twenty two patients with pure hepatitis C viral infection ) ,GroupIIb( twenty five patients with mixed hepatitis C viral infection and hepatic schistosomiasis), and GroupIIc(ten patients with pure hepatic schistosomiasis).

All the studied groups were subjected to full clinical examination.

Laboratory investigations included estimation of serum levels of MMP-1, TIMP-1 and Caspase-3 by ELISA.

Liver profile tests, hematological tests and serological viral tests were also done to the studied groups.

Results: In the present study, it was found that Matrix Metalloproteinase -1 (MMP-1) level was significantly increased in group II and IIa when compared to groupI.

Also MMP-1was significantly increased in group IIa when compared to group IIc.

Tissue inhibitor of matrix metallo-proteinase-1 (TIMP-1) was significantly increased in the whole patients group as well as its subgroups (groups II, IIa, IIb and IIc) when compared to group I.

Also TIMP-1 was significantly increased in both group IIa and IIb when compared to group IIc.

A positive correlation was found between MMP-1 and TIMP-1 in groupII and groupIIa Also, there was a positive correlation between TIMP-1and Child Pugh score in group II and IIb.

Caspase-3 showed no significant difference between the whole patients group and the control group.

However, it was significantly increased in group IIa when compared to group IIb.

The ratios between MMP -1/Caspase-3 and TIMP -1/Caspase -3 increased significantly in both groupII and IIb when compared to group I.

Conclusions: 1.

The significant increase of serum TIMP-1 in the whole patients group as well as its subgroups when compared to the control group reflects its role in promoting liver fibrogenesis and progression of hepatic insult .This is also clear from the significant positive correlation found between TIMP -1 and Child Pugh score.

These points to its role in detecting patients with liver cirrhosis.

2.

The high values of TIMP -1 in patients with normal aminotransferases may reflect the role of regular determination of TIMP-1 as an indicator of increasing fibrosis and the development of cirrhosis.

3.

The significant increase of serum MMP-1in the whole patients group and in patients with pure hepatitis C infection when compared to the control group despite the increase in serum TIMP-1 denotes that TIMP-1 increases in a trial to compensate the increased MMP -1 levels.

This is further confirmed by the positive correlation found between MMP-1 and TIMP-1 in this group of patients.

4.

The significant increase in both MMP-1/Caspase -3 ratio and TIMP- 1/Caspase-3 ratio in the whole patients group when compared to the control group denotes that adding Caspase-3 to MMP-1/TIMP-1 assessment may enforce this ratio by evaluating one important effector in the apoptotic machinery and combining its effect with the state of matrix degradation.