PYRIDINOLINE COLLAGEN CROSS-LINKS IN PATIENTS WITH CHRONIC VIRAL-HEPATITIS AND CIRRHOSIS

Background/Aims: The mature form of collagen cross-linking increases t he resistance of collagen to degradative enzymes, and thus readers the protein in the fibrotic lesions extremely stable and the fibrosis vir tually irreversible. It is crucial to elucidate the extent of cross-li nking in fibrotic and cirrhotic livers if we are to control the subseq uent removal of the excessive deposited collagen, whether by natural e nzymes or induced by therapy. We aimed to quantitate pyridinoline, a m ature form of the cross-linking, in normal control livers, viral fibro tic livers with various degrees of fibrosis and viral cirrhotic livers . Methods: Needle liver biopsy samples from 75 patients with chronic v iral hepatitis and 13 patients with viral liver cirrhosis, and six nor mal control livers were analyzed. Collagen and pyridinoline contents w ere determined by high-performance liquid chromatography. Results: Sig nificantly higher levels of pyridinoline cross-links per collagen mole cule were found in the viral cirrhotic livers (0.60 [0.46, 0.65] pmol/ pmol of collagen; median [25%, 75%]) compared with those in normal liv ers (0.39 [0.24, 0.43] pmol/pmol of collagen, p=0.03491). But no diffe rences were found in levels between cirrhosis and chronic hepatitis wi th various degrees of fibrosis. These data suggest that liver collagen may be susceptible to degradation to a similar degree in viral cirrho sis and in chronic viral hepatitis. Conclusion: The extent of the pyri dinoline cross-linking of hepatic collagen does not seem to be respons ible for the irreversibility of viral liver fibrosis.