Liver stellate cells and aminoterminal peptide of type III procollagen in chronic hepatitis C treated with interferon.
OBJECTIVE
Fibrogenesis plays a crucial role in development of cirrhosis, and liver stellate cells, activated to myofibroblasts expressing alpha-smooth muscle actin, are responsible for deposition of fibrous matrix; aminoterminal peptide of type III procollagen is a serum marker of active fibrogenesis. Interferon can slow ongoing fibrogenesis in chronic viral hepatitis, but it remains unclear whether the drug acts by a direct effect on stellate cells or by inhibiting the necro-inflammatory process. The aim of this study was to evaluate, in selected cases of chronic hepatitis C, whether changes in stellate cell expression induced by interferon correlated with changes in serum levels of procollagen or with clinical response to the therapy, in order to further investigate the mechanism of interferon's effect on fibrogenesis.


METHODS
We studied 30 patients with chronic hepatitis C, treated with interferon and followed for more than 6 months. Before and after-treatment evaluation included histological scores for portal activity, lobular activity and fibrosis; immunohistochemical scores for alpha-actin expression by activated stellate cells in liver biopsy; and radioimmunoassay for procollagen in serum. According to the clinical response to interferon, the patients were subdivided into sustained responders, delayed relapsers, early relapsers and non-responders.


RESULTS
We found that alpha-actin scores, portal and lobular activity scores and procollagen levels were all significantly lower after the treatment in responder patients, whereas in non-responders the after-interferon values were not different from the basal values. Moreover we found that the patients who were still clinical responders at the time of after-therapy evaluation, but relapsed subsequently (delayed relap-sers), still showed a pattern of "low fibrogenesis", like the sustained responders. On the contrary, the patients who had already relapsed at the time of after-interferon evaluation (early relapsers) showed a pattern of "high fibrogenesis", like the non-responders.


CONCLUSIONS
Since all the patients had received a similar treatment for a similar period, our results suggest that fibrogenesis activity in a defined time is related to the clinical response present in that time, and is influenced by short-term variations in necro-inflammatory activity induced by interferon, rather than by interferon itself.
Gabrielli
Giovanni B
GB
Department of Clinical and Experimental Medicine, University of Verona, Italy. GGABRIELLI@UNIVR.IT
Casaril
Massimo
M
Stanzial
Anna Maria
AM
Colombari
Romano
R
Pasino
Michela
M
Corrocher
Roberto
R
D000199:Actins / Q000097:blood; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000199:Actins; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010446:Peptide Fragments; D011347:Procollagen; D011994:Recombinant Proteins; C041876:procollagen Type III-N-terminal peptide; D000410:Alanine Transaminase