Faculty Bibliography

The lower limit of detection of most polymerase chain reaction (PCR) assays for hepatitis C virus (HCV) RNA is 50 IU/ml, compared to 5 IU/ml for the transcription-mediated amplification (TMA) method. We retrospectively reviewed 57 patients to assess the predictive value of a positive TMA in the setting of a negative PCR during antiviral therapy. Patients were divided into (1) PCR-/TMA+ (discordant; n=21) and (2) PCR-/TMA-(concordant; n=36). Sustained virologic response (SVR) was decreased in the discordant group (48% vs. 75%; P=0.04). In discordant patients, SVR was more frequent in patients who had one positive TMA than in those who had two or more positive TMAs or one positive TMA and recurrent HCV RNA detectability by PCR during treatment (78% vs. 25%; P=0.03). Breakthrough occurred more frequently in discordant patients (24% vs. 3%; P=0.02). A positive TMA on two or more occasions in patients who have become PCR-negative on therapy indicates a high likelihood of treatment failure.

UNLABELLED: This prospective, multicenter, community-based and academic-based, open-label, investigator-initiated, U.S. study evaluated efficacy and safety of pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in adults with chronic hepatitis C. Patients (n = 5027) were randomly assigned to receive PEG-IFN alfa-2b 1.5 microg/kg/week plus flat-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (genotype 2/3 patients). Primary end point was sustained virologic response (undetectable [<125 IU/mL] serum hepatitis C virus RNA at 24-week follow-up). Sustained virologic response, but not end-of-treatment, rates were significantly higher with weight-based than with flat-dose RBV (44.2% versus 40.5%; P = 0.008). Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P = 0.005) and 31.2% and 26.7%, respectively, in genotype 1 patients with high baseline viral load (P = 0.056). In genotype 2/3 patients, rates were not significantly different (61.8% and 59.5%, respectively) regardless of treatment duration. Besides greater hemoglobin reductions with weight-based RBV, safety profiles were similar across RBV dosing groups, including the 1400-mg/day group. CONCLUSION: PEG-IFN alfa-2b plus weight-based RBV is more effective than flat-dose RBV, particularly in genotype 1 patients, providing equivalent efficacy across all weight groups. RBV 1400 mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3 patients, 24 weeks of treatment with flat-dose RBV is adequate; no evidence of additional benefit of extending treatment to 48 weeks was demonstrated.