DECREASE IN SERUM LEVELS OF MARKERS OF HEPATIC CONNECTIVE-TISSUE TURNOVER DURING AND AFTER TREATMENT OF CHRONIC HEPATITIS-B WITH INTERFERON-ALPHA

Interferon-alpha induces remission in 30% to 40% of patients with chro nic hepatitis B, but its effect on hepatic connective tissue turnover has not been well documented. We studied the changes in serum procolla gen III propeptide and laminin-PI peptide (Lam-P1) in 33 patients with chronic hepatitis B (11 nontreated controls and 22 treated patients) during a 4-mo randomized trial of interferon-alpha. Liver biopsy speci mens were obtained at the start of treatment and 12 mo later. Liver bi ochemical tests, procollagen III propeptide, laminin-P1 peptide and he patitis B virus DNA polymerase were determined before treatment with i nterferon was begun (mo -3), at the initiation (0 time) and completion of treatment (mo 4) and also at 8, 12 and 18 mo. Treated patients wer e classified as ''responders'' and ''nonresponders'' on the basis of c learance of HBV e antigen from serum. There were no significant change s in the control group, whereas the responders had persistent decrease s in ALT, AST, hepatitis B virus dna polymerase, procollagen I propept ide and laminin-P1 peptide. The nonresponders had transient ALT, AST a nd hepatitis B virus dna polymerase reductions that returned toward ba seline levels during follow-up, but procollagen III propeptide and lam inin-P1 peptide persisted below the baseline at mo 18. Significant cor relations between procollagen III propeptide and laminin-P1 peptide wi th ALT, AST and liver histologic specimens were noted at baseline but not after 12 mo. Changes in procollagen III propeptide levels also cor related with changes in AST, ALT and liver histologic specimens. On th e basis of logistic regression, neither markers of connective tissue t urnover nor histology improved the accuracy of AST, ALT and hepatitis B virus dna polymerase for predicting response to interferon. We concl ude that interferon treatment induces a persistent suppression in seru m markers of hepatic connective tissue turnover in chronic hepatitis B patients independent of its effect on viral replication and hepatic n ecroinflammation.