Quantification of the initial decline of serum hepatitis c virus RNA and response to interferon alfa

Abstract

Although several virus‐ and host‐related predictive factors for the response to interferon alfa (IFN‐α) have been defined in patients with chronic hepatitis C, no pretreatment parameter can definitely predict the response to antiviral treatment. Assessment of the initial response by quantification of serum hepatitis C virus RNA before and 4 weeks after initiation of therapy may be a clinically applicable and reliable parameter to predict long‐term response. Therefore, the aims of the present study were to test the predictive value of a decline in HCV RNA of at least 3 log in the first 4 weeks of treatment (▵HCV RNA) in patients treated with 3 × 10⁶ units of recombinant IFN‐α2a (rIFN‐α2a) three times per week subcutaneously and to compare ▵HCV RNA with other established predictive factors, such as HCV genotype and pretreatment viremia. Serum HCV RNA was measured by a validated quantitative reverse transcription–polymerase chain reaction (RT‐PCR). Geno/subtyping of HCV was performed by direct sequencing of the nonstructural (NS) 5B region of PCR‐amplified isolates and subsequent phylogenetic analysis. Stable HCV RNA levels (▵HCV RNA ≤ 1 log) within the first 4 weeks of IFN‐α treatment were present in 42 of 70 patients. A decline in HCV RNA levels between 1 to 3 log and more than 3 log was observed in 9 (13%) and 19 patients (27%), respectively. In 21 of 70 patients (30%), HCV RNA was not detectable at the end of 12 months' treatment. Three of 26 patients (11%) with a pretreatment viremia of ≤10⁶ copies/mL (all HCV subtype 3a) and 6 of 44 patients (14%) with a pretreatment viremia of >10⁶ copies/mL (HCV subtypes 1b, 2a, 2c, 3a [two patients], and 4) achieved a virological sustained response to interferon‐α2a treatment. All patients with a virological sustained response had an initial ▵HCV RNA of more than 3 log. In a stepwise discriminant‐function analysis, the initial ▵HCV RNA was confirmed as the strongest predictor of virological sustained response (P < .0001). In conclusion, the data of the present study suggest that IFN‐α treatment can be terminated after 4 weeks in patients with a decrease in HCV RNA levels of less than 3 log, when apparent HCV eradication is considered the therapeutic target. The predictive value of ▵HCV RNA clearly exceeds the significance of HCV genotype and pretreatment viremia as predictors of successful IFN‐α treatment.