A randomized, controlled trial of maintenance inteferon therapy for patients with chronic hepatitis C virus and persistent viremia

Background & Aims: At least half of patients with chronic hepatitis C virus (HCV) fail to respond to interferon or interferon/ribavirin therapy. Histo logical improvement is observed in some nonresponders. We conducted a rando mized, controlled trial to determine if maintenance interferon therapy coul d prevent histological progression in this subset of nonresponders. Methods : Fifty-three patients with chronic HCV were enrolled. All were HCV-RNA pos itive after 6 months of treatment with interferon alfa-2b but had a histolo gical response. Twenty-seven of the patients were randomly assigned to cont inue interferon (3 MU 3 times weekly) for 24 months; 26 patients discontinu ed treatment and were observed prospectively. Alanine aminotransferase (ALT ) level and HCV-RNA titer were monitored, and liver biopsy was repeated eve ry 12 months. Results: Before Interferon therapy, the 2 groups were well ma tched for all demographic factors, serum ALT (94.0 +/- 15.6), log HCV-RNA t iter (5.85 +/- 0.15 copies/mL), histology score (9.5 +/- 0.2), and percenta ge with cirrhosis (25%). After 6 months of treatment, significant reduction s (P < 0.05) in serum ALT level (62.6 +/- 9.6), log HCV-RNA titer (4.79 +/- 0.13 copies/mL), and hepatic inflammation (4.0 +/- 0.2) were observed. The se improvements were maintained in the patients randomized to continue inte rferon. Stopping treatment was associated with an increase in serum ALT, lo g HCV-RNA, and hepatic inflammation back to baseline. After 30 months of tr eatment, mean fibrosis score declined from 2.5 to 1.7 and 80% of patients h ad histological improvement (P < 0.03). Discontinuation of interferon was a ssociated with an increase in mean fibrosis score from 2.2 to 2.4 and worse ning of hepatic histology in 30% of patients (P < 0.01). Conclusions: These data support the hypothesis that maintenance interferon may prevent histol ogical progression of chronic HCV in patients who remain viremic.