Interferon-alpha suppresses liver cell proliferation in patients with chronic hepatitis C virus infection.
Interferon (IFN) therapy has been shown to reduce the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C, including virological nonresponders (NR). Whether IFN suppresses liver cell proliferation, i.e. the relevant risk factor for HCC, is unknown. The aim of the study was to evaluate the effect of IFN therapy on liver cell proliferation in chronic hepatitis C. The proliferating cell nuclear antigen-labelling index (PCNA-LI) was assessed prior to and at the end of therapy in the liver of 29 patients with chronic hepatitis C who received 3 MU IFN-alpha2b thrice weekly for 24-48 weeks. Overall, the median value of PCNA-LI was significantly reduced from 2.6% to 1.1% at the end of therapy (P < 0.0001). At baseline, PCNA-LI median values were similar in the 15 virological responders compared with the 14 NRs (2.3%vs 3.4%, P = 0.121) and at the end of therapy, median changes of PCNA-LI (-1.4%vs-1.1%, P = 0.089) were also similar although there was a higher decline of the proliferation index in responders with respect to NRs at the end of therapy (0.7%vs 1.6%, P = 0.004). In the two groups, the rate of fibrosis score reduction was also similar (7%vs 20%, P = 0.326). In contrast, the histological activity index was more often reduced in responders than in NRs both at the >or=2 and >or=4 points reduction level (80%vs 36%, P = 0.02 and 53%vs 14%, P = 0.03, respectively). The study showed a significant suppression of liver cell proliferation in IFN-treated patients with chronic hepatitis C. Although the strongest IFN effect was observed in virological responders, a reduction of proliferative activity was also seen in virological NRs.
Donato
M F
MF
Department of Gastroenterology and Endocrinology, Division of Hepatology, A.M. & A. Migliavacca Center for Liver Disease, IRCCS Ospedale Maggiore and FIRC Research Unit, University of Milan, Milan, Italy. francesca.donata@policlinico.mi.it
Degott
C
C
Arosio
E
E
Martinot
M
M
Monti
V
V
Morabito
A
A
Marcellin
P
P
Colombo
M
M
D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006526:Hepatitis C / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D006521:Hepatitis, Chronic / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D016896:Treatment Outcome
D016898:Interferon-alpha; D012367:RNA, Viral