Hepatitis C Virus Genotype, Hepatitis C Virus RNA Titers, and Response to Interferon

  1. Gloria Taliani, MD, PhD;
  2. Maria Concetta Badolato, BD; and
  3. Caterina Pasquazzi, MD
  1. La Sapienza University; Rome, Italy

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    TO THE EDITOR:

    In their interesting report on the clinic characteristics of and the response to interferon treatment in patients with different hepatitis C virus (HCV) genotypes, Zein and colleagues [1] suggest that circulating HCV RNA levels could modulate the sensitivity of HCV genotypes to interferon treatment.

    We recently enrolled 61 patients with HCV infection and chronic liver disease without cirrhosis (40 men; mean age ±SD, 48.7 ± 11.4 years). Patients were randomly assigned to receive 9 million U of interferon-α 2b per week (28 patients) or 15 million U per week for 6 months. The HCV genotype was assessed by line-probe assay (Inno LiPA, Innogenetics, Ghent, Belgium), and HCV RNA levels were measured by branched-DNA assay (Quantiplex, version 2, Chiron Corp., Emeryville, California). Twenty-six patients were infected with genotype 1b; 6 patients, with genotype 1a; 17 patients, with genotype 2a/c; 7 patients, with genotype 3; and 5 patients, with genotype 4. Thirty-eight patients (62.3%) showed a biochemical and virologic response to treatment, including 43.7% of patients with genotype 1 and 82.7% of patients with other genotypes (P = 0.001). No difference between groups was seen in the rate of response.

    Although the baseline viremia in responders was significantly lower than that in nonresponders (2.7 ± 3.3 and 5.4 ± 7.1 genome equivalents × 106/mL, respectively; P = 0.02), this difference was lost when patients were stratified according to genotype. Patients infected with genotype 2 had a high response rate (93.7%) even though their HCV RNA titers were similar to those of patients with genotype 1a (1.3 ± 1.4 and 2.7 ± 2.4 genome equivalents × 106/mL; P = 0.1). None of the latter patients responded to therapy. In contrast, patients with genotype 1a had significantly lower RNA titers than patients with genotype 1b (6.1 ± 7.1 genome equivalents × 106/mL; P = 0.03); 14 of these patients responded to interferon (P = 0.01).

    Our data, obtained from prospectively collected serum samples, suggest that in patients without cirrhosis, HCV genotype is the main predictor of response to interferon therapy. Previous studies pointed out that low pretreatment viremia was a relevant independent factor associated with response and showed that most responders had undetectable baseline HCV RNA levels according to branched-DNA assay [2]. However, these results were generally obtained by examining stored serum samples; even storage at −20°C may affect branched-DNA assay results because of significant loss of RNA [3].

    Our study showed that by the end of 1 month of therapy, the responders either showed a mean decrease in HCV RNA titer that was higher than 85% of the baseline value or were HCV RNA negative. All nonresponders were still HCV RNA positive and had a mean decrease in titer less than 40%. Therefore, this kinetic activity of HCV RNA in the early treatment period seemed to be a better predictor of response than the HCV RNA baseline titer itself. Confirmation of this finding in a larger series of patients may give an interesting clue to the management of patients receiving interferon.

    Gloria Taliani, MD, PhD

    Maria Concetta Badolato, BD

    Caterina Pasquazzi, MD

    La Sapienza University; Rome, Italy

    The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:

    •Include no more than 300 words of text, three authors, and five references

    •Type with double-spacing

    •Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.

    Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.

    Annals welcomes electronically submitted letters.

    References

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