Treatment with interferon-alpha 2b of naive non-cirrhotic patients with chronic hepatitis C according to viraemia and genotype. Results of a randomized multicentre study

Objective To establish whether tailoring the dosage of interferon (IFN)-alp ha Sb in non-cirrhotic naive patients with chronic hepatitis C according to hepatitis C virus (HCV) genotype and viraemic level improves the rate of s ustained response (normal alanine aminotransferase values and HCV-RNA negat ivity 6 months after the end of therapy). Patients 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 (Ge nEq/ml) treated with 3 Million Units (MU) IFN three times weekly (t.i.w.) f or 1 year; Group 2, 42 patients with genotype 1 and viraemia < 1 000 000 Ge nEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 3, 46 patients with g enotype 1 and viraemia < 1 000 000 GenEq/ml treated with 5 MU IFN t.i.w. fo r 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 wit h 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 dai ly 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 virologica l response (negative HCV-HNA by polymerase chain reaction 6 months after th e 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 observ ed, the adoption of more aggressive IFN protocols, such as induction therap y, does not appear to significantly improve the rate of sustained response in patients with chronic hepatitis C associated with HCV genotype 1 and hig hly viraemic levels compared with standard therapy. Moreover, patients with only one unfavourable predictive factor (genotype 1 or high viraemia) do n ot gain major therapeutic benefits when treated with high doses of IFN. Eur J Gastroenterol Hepatol 13:149-155 (C) 2001 Lippincott Williams & Wilkins.