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To evaluate the efficacy of large dose interferon treatment for patients with chronic hepatitis C virus (HCV) infection, we studied 99 Japanese patients treated with either 6 million units (MU) or 9 MU natural interferon alpha. Serum samples were tested for HCV RNA by polymerase chain reaction (PCR). HCV RNA genotypes were determined by PCR with type-specific preimers, and the HCV RNA level was measured by competitive PCR. HCV RNA was detected in all patients, prior to the initiation of treatment. We examined interleukin-1 receptor antagonist (IL-1 Ra) by enzyme-linked immunosorbent assay. Forty-four patients were treated with 9 MU natural interferon alpha for 24 weeks (group A), and fifty-five patients were treated with 6 MU natural interferon alpha for 24 weeks (group B). There were no significant differences in HCV RNA levels, HCV RNA genotype or histological activity index (HAI) score between the two groups. Of the 94 patients who completed this treatment, nine (23.1%) in group A and 14 (25.5%) in group B sustained elimination of HCV RNA throughout a 6-month follow-up. There were no differences in the rate of complete response when comparing HCV RNA genotype, levels and HAI score and no significant differences in elevation of IL-1 Ra levels between the two groups. Five of group A patients refused further treatment because of severe side effects such as retinal hemorrhage, while no patient in group B had severe side effects. Thus, large dose natural interferon alpha treatment confers no additional benefit to the patient, compared with the current use of a lower dose.

To determine serum soluble interleukin-2 receptor (sIL-2 R) levels in hepatitis C virus (HCV) infection, serum sIL-2 R was measured in 260 subjects with chronic HCV infection, including 100 patients who had previously been treated with natural interferon (IFN) alpha, and in 51 HCV RNA-negative controls. Serum sIL-2 R levels in asymptomatic HCV carriers, patients with chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) were significantly higher than those of healthy controls and subjects who were positive for anti-HCV and negative for HCV RNA (P < 0.01, respectively). Moreover, serum sIL-2 R levels were also significantly higher in patients with HCC than in other HCV RNA-positive groups. There was some correlation between serum sIL-2 R levels and histological activity index scores (r = 0.287, P < 0.01) and serum alanine aminotransferase levels (r = 0.272, P < 0.01). In patients in whom HCV RNA was eliminated following IFN treatment, serum sIL-2 R levels decreased to those seen in healthy controls by one year post treatment. Serum sIL-2 R levels increase due to HCV infection, and the amount of increase corresponds to the degree of inflammation.

Nine patients with chronic hepatitis C virus (HCV) infection and no complete response to the first treatment with natural interferon (IFN)-alpha, were prescribed a second treatment with IFN. Five patients (Group A) with unsustained levels serum alanine aminotransferase (ALT) after the first treatment were administrated the same species of IFN but in a higher dose. The remaining four patients (Group B), with no normalization of ALT throughout the observation period of the first treatment, were administrated IFN-beta. HCV RNA was eliminated in three patients of group A and in two of group B patients during 6 months follow up and ALT reverted to normal levels. These results suggest that retreatment with a higher dose of the same species of IFN-alpha can be effective in case of a relapse and that IFN-beta can be effective for those not responding to IFN-alpha.