Viral hepatitlerde matriks metalloproteinazların ve inhibitörlerinin ekspresyon paternleri ve bunların fibrozis ile ilişkileri

Amaç: Bu arastırmanın amacı, kronik viral hepatitli hastaların karaciğer biyopsilerinde MMP ve TIMP ekspresyonlarının siddeti ve yaygınlığı ile fibrozis evresinin ve nekroinflamatuar derecesinin iliksisini saptamaktır. Gereç ve Yöntem: 67 kronik viral hepatitli hastanın karaciğer biyopsilerinde MMP’lerin ekspresyon yaygınlığını, siddetini ve lokalizasyonunu değerlendirip, TIMP-1 ve TIMP-2 ile korelasyonunu arastırdık. Yirmiyedi kronik B hepatitli, 40 kronik C hepatitli hastanın karaciğer biyopsileri ve 5 normal kontrol karaciğer biyopsisi immünhistokimyasal olarak MMP-2, MMP-9, TIMP-1 ve TIMP-2 ile boyandı. Hastalara ait klinik bilgiler dosyalarından elde edildi. Bulgular: HBV veya HCV ile iliskisinden bağımsız olarak MMP-9 ekspresyonu hepatositlerde çok az oranda (%3) iken, MMP-2 olguların %43’ ünde hepatositlerde ve portal alanlardaki iğsi hücrelerde eksprese oldu. TIMP-1 ve TIMP- 2 ile hepatositlerde, sinüzoidal hücrelerde ve portal alanlardaki iğsi hücrelerde değisen oranlarda (sırasıyla %12 ve 21) boyanma görüldü. Sadece TIMP-1 ekspresyonu MMP-2 ekspresyonu ile koreleydi (p=0,01). Diğer yandan ne MMP-2 ve MMP-9 ne de TIMP-1 ve TIMP-2 ekspresyonları inflamasyonun ve fibrozisin yaygınlığı ile korelasyon göstermedi. Sonuç: MMP ve TIMP’ lerin kan seviyeleri ile siroz gelisiminin korele olduğu birçok grup tarafından gösterilmis olsa da bizim bulgularımıza göre viral hepatit örneklerindeki MMP-2, MMP-9, TIMP-1 ve TIMP-2 ekspresyon paternlerindeki değisiklikler serumdaki konsantrasyon değisikliklerini açıklamaz ve hastalığın ilerlediğini göstermez. Bu nedenle kandaki seviylerinin karaciğere spesifik olduğu net değildir.

Expression patterns of matrix metalloproteinases and their inhibitors in vıral hepatitis and their relation with fibrosis

Purpose: To determine the association between the expression patterns of matrix metalloproteinases (MMPs) and extent of fibrosis and inflammation in chronic viral hepatitis. Materials and Methods: We examined the expression and localization of MMP-2 and MMP-9 and correlated the data with their main inhibitors, tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), in 67 chronic viral hepatitis patients. Immunohistochemistry was performed for MMPs and TIMPs in liver biopsies of 5 normal controls, 27 patients with chronic hepatitis B, and 40 patients with chronic hepatitis C. Results: In viral hepatitis, MMP-9 expression in hepatocytes was very small (3%), whereas MMP-2 was expressed in hepatocytes and in some spindle cells in the portal tracts in 43% of the cases. Variable degrees of staining were observed in hepatocytes, sinusoidal cells, and spindle cells in the portal tract for TIMP-1 and TIMP-2 (12% and 21%, respectively). Only TIMP-1 expression correlated with the expression of MMP-2 (p=0.01). On the other hand, neither MMP-2 and MMP-9 nor TIMP-1 and TIMP-2 expressions showed any correlation with the extent of inflammation and fibrosis.Conclusion: Our findings showed that alterations in the expression patterns of MMP-2, MMP-9, TIMP-1, and TIMP-2 in the samples of viral hepatitis do not explain the changes in serum concentrations and do not mirror the progression of the disease. Thus, it is still unclear whether their circulating levels are liver specific.

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