Background/aims: The relative role of hepatitis C virus (HCV) load and subtype as predictors of the efficacy of interferon therapy has been clarified in patients with chronic hepatitis C, but the effectiveness of interferon therapy in cirrhotic patients is still unclear.
Methods: To resolve this issue, we undertook a multicenter, randomized, and prospective study of 114 cirrhotic patients with hepatitis C virus infection. The patients were selected to undergo two different periods (6 or 12 months) of IFN therapy according to viral load. Patients with "low" viral load (< or = 10(5.8) copies/ml serum) were randomly divided into three groups, receiving 6 or 9 million units (MU) interferon three times a week for 6 months (total dose: 468 or 702 MU), or of a modified regimen using 6MU of IFN over 6 months (total dose 564 MU), while patients with "high" viral load (< or = 10(6.3) copies/ml serum) were also randomly divided into two groups of 6 or 9 MU of IFN three times a week for 12 months (total dose: 936 or 1,404 MU).
Results: HCV-RNA negativity rate at the completion of treatment with 6 or 9 MU IFN was 65% in patients with "low" viral load, in contrast to 14% in patients with "high" viral load. Sustained virological response was found in 40% of patients with "low" viral load irrespective of the three different regimens, in contrast to only 1 out of 35 patients (3%) with "high" viral load. Viral eradication was found in approximately 50% of patients having a low virus load (< or = 10(4.3) copies/ml) and with HCV subtype 2a. Univariate and multivariate analysis revealed that pretreatment viral load was a significant factor contributing to efficacy of IFN therapy.
Conclusions: Sustained response was scarcely achieved in cirrhotic patients with high viral loads even after a 12-month course of intensive IFN therapy. This result indicates that there is a certain cut-off level of HCV RNA load which can not be eradicated.