title: Correlates and prognostic value of the first-phase hepatitis C virus RNA kinetics during treatment.
abstract: BACKGROUND
  Analysis of hepatitis C virus (HCV) RNA kinetics during antiviral therapy may allow estimation of the probability of response.
  
  
  METHODS
  To assess clinical and virological correlates and the predictive value of first-phase HCV RNA kinetics during pegylated interferon and ribavirin treatment, we studied 119 patients with chronic hepatitis C who were treated with pegylated interferon and ribavirin. HCV RNA level was measured 5 min before and 2, 14, and 28 days after the start of treatment. For each patient the Delta(t0-t2) log(10) HCV RNA value was calculated, which indicates the relative reduction in HCV RNA level from before treatment to day 2 after logarithmic transformation.
  
  
  RESULTS
  A Delta(t0-t2) log(10) HCV RNA value < or =0.8 showed a 95% negative predictive value for virological response, whereas one >2.5 had a 93% positive predictive value for virological response, independent of genotype and histology. The Delta(t0-t2) log(10) HCV RNA value was strictly related to final treatment outcome and could differentiate not only patients with a sustained virological response from nonresponders but also patients who experienced relapse from the former. The Delta(t0-t2) log(10) HCV RNA value was highest among patients infected with genotypes 2 and 3 and was lowest among patients infected with genotype 1. It decreased with increasing grades of fibrosis and steatosis and was also inversely related to gamma-glutamyl transpeptidase (GGT) level and HOMA-IR (homeostasis model assessment for insulin resistance) score. In multivariate analysis, Delta(t0-t2) log(10) HCV RNA value was the strongest predictor of sustained virological response and appeared to be independently related to viral genotype and GGT level.
  
  
  CONCLUSIONS
  HCV RNA kinetics has strong predictive value. It correlates with virological and clinical parameters that are known predictors of antiviral treatment outcome, including insulin resistance. The measurement of HCV load as early as 2 days after the start of pegylated interferon and ribavirin is a useful tool for the prediction of treatment outcome in individual patients and should be used in clinical practice.
authors: Second University of Naples Medical School, Department of Cellular and Molecular Biology, Federico II University Medical School, Naples, Italy. E.emanuele.durante@unina2.it
authors: Emanuele
authors: E
authors: Durante-Mangoni
authors: Rosa
authors: R
authors: Zampino
authors: Giuseppe
authors: G
authors: Portella
authors: Luigi E
authors: LE
authors: Adinolfi
authors: Riccardo
authors: R
authors: Utili
authors: Giuseppe
authors: G
authors: Ruggiero
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a