Changes in histological lesions and serum fibrogenesis markers in chronic hepatitis C patients non-responders to interferon alpha.

Background/aims: The aim of this study was to evaluate the changes in histological lesions and serum N-terminal peptide of type III procollagen (PIIINP) and hyaluronate (HA) levels in virologic non-responder patients treated by Interferon alpha (IFNalpha).

Methods: We enrolled 183 patients treated by IFNalpha and 56 controls, all with paired biopsy specimens. Yearly liver fibrosis progression was estimated before and during a follow-up of 1 year.

Results: By contrast to sustained responders, non-responders (n = 105) did not achieve improvement of histological scores after therapy. Their yearly fibrosis progression rate was similar before and during follow-up (0.18, 95%CI: 0.16-0.20, vs 0.26 (95%CI: 0.12-0.40) fibrosis units/year, NS), and was not different in controls (0.17, 95%CI: 0.06-0.27). The levels of PIIINP and hyaluronate (HA) remained unchanged during follow-up. Histological improvement was observed for the second biopsy in 25% of non-responders, but also in 23% of controls. This improvement was not correlated with decrease of ALT level, viral load, PIIINP, or HA.

Conclusions: Our results suggest that IFNalpha therapy is unable to decrease PIIINP or HA levels and cannot improve the histological outcome in virologic non-responder patients. The histological improvement observed in a subset of patients may be linked to sample fluctuation or lack of reproducibility of histological scores.