Resistance to alpha interferon therapy in HCV chronic liver disease: role of hepatic fibrosis.

The response rate to interferon in HCV chronic liver disease is insufficient to date and the causes of this failure are not fully understood. Hepatic fibrosis hinders the blood-hepatocyte exchange of substances and we hypothesized that this process may also reduce the efficacy of interferon. Serum levels of connective tissue metabolites are related, to some extent, to the amount of extracellular matrix in the liver. Therefore, the usefulness was evaluated of serum tests of connective tissue metabolism compared to standard biochemical and histological parameters in predicting the probability of primary response to interferon. Sixty-eight patients with HCV chronic liver disease were treated with alpha-interferon for 1 year. At multivariate analysis time 0, the serum level of the P1 fragment of laminin was found to be the only factor independently associated with the response to treatment. As is well known, higher serum concentrations of the P1 fragment of laminin are associated with active basement membrane turnover and derangement of the hepatic structure. Therefore, this process seems to reduce the probability of response to interferon and, if confirmed, evaluation of serum the P1 fragment of laminin may be a useful test to predict the response to interferon and to define the therapeutic strategy, especially as far as the dose of interferon is concerned.