Matrix metalloproteinases in liver and serum in chronic active hepatitis Cand HCV-induced cirrhosis

To study the value of matrix metalloproteinases as indicators of hepatic fi broproliferation, expression of MMP-1, MMP-2, MMP-7 and MMP-9 was studied i n healthy controls, patients with chronic hepatitis C (CAH) and in HCV-indu ced cirrhosis. Western blot revealed an increase for MMP-1 in CAH with hist ologically detectable fibrosis and diminished amounts in cirrhosis. MMP-2 w as unchanged in CAH and cirrhosis, while there was an increase of MMP-7 in 8 of 18 cirrhotic liver samples. Northern analysis demonstrated in cirrhosi s an increase of MMP-7 mRNA more strongly than MMP-2 mRNA. ELISA studies de monstrated a trend towards an increase in circulating MMP-2 levels and a re duction in circulating MMP-9 levels with advancing fibrosis. RT-PCR demonst rated transcripts for MMP-1, MMP-2 and MMP-7 in hepatic tissue and isolated stellate cells. MMP-9 transcripts were only found in white blood cells. He patic expression of MMP-1, MMP-2 and MMP-7 is increased in chronic hepatiti s C, but the resulting proenzyme levels are not sufficiently different to a llow discrimination between patients with and without fibroproliferation. M MP-9 shows significant changes in serum, with a progressive reduction from controls to cirrhosis, but is most likely derived from extrahepatic sources . (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.