Treatment with interferon-alpha2b of naive non-cirrhotic patients with chronic hepatitis C according to viraemia and genotype. Results of a randomized multicentre study. The North West Italian Hepatological Group.
OBJECTIVE
To establish whether tailoring the dosage of interferon (IFN)-alpha2b in non-cirrhotic naive patients with chronic hepatitis C according to hepatitis C virus (HCV) genotype and viraemic level improves the rate of sustained response (normal alanine aminotransferase values and HCV-RNA negativity 6 months after the end of therapy).


METHODS
A total of 538 consecutively collected HCV-positive patients with non-cirrhotic chronic hepatitis who had not been previously treated.


METHODS
Quantitative viraemia and genotype were determined in each patient by a core laboratory. The patients were randomized to: Group 1, 86 patients with genotype non-1 and viraemia < 1,000,000 HCV genome equivalents/ml (GenEq/ml) treated with 3 Million Units (MU) IFN three times weekly (t.i.w.) for 1 year; Group 2, 42 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml treated with 3 MU IFN t.i.w. for 1 year; Group 3, 46 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml treated with 5 MU IFN t.i.w. for 1 year; Group 4, 85 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 5, 88 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 5 MU IFN t.i.w. for 1 year; Group 6, 94 patients with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 7, 97 patients with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 5 MU IFN daily for 2 months followed by 5 MU t.i.w. for a further 10 months.


RESULTS
According to an intention-to-treat analysis, a sustained virological response (negative HCV-RNA by polymerase chain reaction 6 months after the end of therapy) was observed in 42% of Group 1 patients, in 21% of Group 2 patients versus 24% of Group 3 patients [P = not significant (NS)], in 28% of Group 4 patients versus 35% of Group 5 patients (P = NS), and in 8.5% of Group 6 patients versus 12% of Group 7 patients (P = NS).


CONCLUSIONS
Even though a trend towards a therapeutic improvement is observed, the adoption of more aggressive IFN protocols, such as induction therapy, does not appear to significantly improve the rate of sustained response in patients with chronic hepatitis C associated with HCV genotype 1 and highly viraemic levels compared with standard therapy. Moreover, patients with only one unfavourable predictive factor (genotype 1 or high viraemia) do not gain major therapeutic benefits when treated with high doses of IFN.
Dipartimento di Gastroenterologia, Ospedale Molinette, Torino, Italy. dagio@inrete.it
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Saracco
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Ciancio
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Ghisetti
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Rocca
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Cariti
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Andreoni
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Tabone
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Roffi
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Calleri
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Ballaré
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Terreni
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Sartori
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Tappero
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Traverso
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Poggio
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Orani
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Maggi
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Di Napoli
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Arrigoni
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Rizzetto
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D019562:Viral Load; D014766:Viremia
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D000410:Alanine Transaminase