Ira M. Jacobson, M. W. Russo, E. Lebovics, S. Esposito, H. Tobias, F. Klion, Robert S. Brown Jr, D. Dieterich, C. Brass, NY Normal ALT Study Group, New York, NY; Westchester, NY; Flushing, NY; Kenilworth, NJ

Most studies establishing the role of antiviral therapy in patients with chronic hepatitis C (CHC) have excluded patients with normal ALT levels. It is estimated that anywhere from <5% to 20% of hepatitis C patients with normal ALT’s have significant hepatic fibrosis. Small trials with interferon monotherapy suggested limited efficacy and/or de novo ALT elevations (treatment induced rising of ALTS) in response to treatment . There is little published data on combination therapy in these patients.

The aim of this study was to evaluate the efficacy of two doses of interferon alfa-2b (IFN) combined with ribavirin (RBV) in patients with CHC and normal ALT levels. Patients with biopsy-proven CHC who were PCR-positive for HCV RNA and at least 2 normal ALT levels 3 or more months apart were randomized to: Group 1: IFN 3 MU tiw plus RBV 1000-1200 mg depending on weight < or > 75 kg, or Group 2: IFN 5 MU tiw plus RBV 1000-1200 mg Patients were treated for 24 weeks and a PCR obtained. Therapy was stopped if the PCR was positive and continued for an additional 24 weeks if the PCR was negative. A final PCR (NGI) was obtained 24 weeks after cessation of therapy.

56 patients were randomized and received at least one dose of medications; 43 (77%) received at least 24 weeks of treatment. The majority of the patients were female (60%). 15% of patients were F3/F4. The rates of sustained response (SR) in the overall study population, by treatment group, and by genotype are shown in the Table. Of 10 African-American patients, 1/10 (10%) had SR. In the overall study group, 3 patients had end of treatment response, followed by relapse, and another 3 had breakthrough relapse. There were 3 serious adverse events (MI, confusion, suicidal ideation). 4 patients developed thyroid dysfunction. 5 patients had mild, transient ALT elevations. No sustained ALT elevations were noted.

In summary:

1. Patients with normal ALT had a rate of SR only slightly lower than SR rates in patients with elevated ALT.
2. The SR rate in patients with genotype 1 approached that seen in patients with genotype 1 and elevated ALT.
3. The higher dose of interferon appeared to be more effective in patients with genotype 1 infection so this leaves open the question, what is the optimum dose?
4. Side effects were similar to those seen in other populations, and de novo ALT elevations were transient and not clinically significant.
5. Patients with CHC should not be excluded from treatment on the basis of ALT alone.
6. Combination therapy with peginterferon and ribavirin should be evaluated in this group of patients.