HISTOLOGICAL-CHANGES BUT NOT VIRUS ERADICATION REFLECT BIOCHEMICAL IMPROVEMENT IN CHRONIC HEPATITIS-C PATIENTS SHOWING A LONG-TERM RESPONSETO INTERFERON-ALPHA THERAPY

Aims: To assess the relationship between changes in liver histology an d virological parameters of HCV infection in patients with a sustained biochemical response to alpha-interferon treatment for chronic hepati tis, with the aim of identifying the most reliable indicator of treatm ent efficacy. Methods: Quantitative serial testing of HCV-RNA in plasm a samples collected on a monthly basis over the last period of post-tr eatment follow-up were tested in sixteen subjects with greater than or equal to 12 months aminotransferase normalisation following discontin uation of interferon therapy. The quantitative HCV-RNA determination i n plasma was performed by a competitive reverse-transcription polymera se-chain reaction. Pretreatment and 12-month post-treatment liver hist ologies were blindly evaluated using a semi-quantitative scoring syste m. At these times a qualitative HCV-RNA analysis was also carried out. Results: The post-treatment histological grading score was significan tly reduced. Nevertheless, all patients except one rested positive for HCV-RNA in plasma (mean 1.7 x 10(6) molecules/ml): nine were positive in all the serial determinations, while the remaining 6 were intermit tently positive. No relationship between genotype, viral load pattern of viremia (intermittent or continuous) and change in histological sco re Ir:as found. Conclusions: Changes in liver histology are the most r eliable indicator of the efficacy of interferon treatment in hepatitis C related liver disease. HCV-RNA clearance based on serial sampling d oes not appear to be a reliable indicator even in the presence of a su stained biochemical response and histological improvement.