title: High-dose interferon-alpha2b induction therapy in combination with ribavirin for treatment of chronic hepatitis C in patients with non-response or relapse after interferon-alpha monotherapy.
abstract: OBJECTIVE
  To evaluate the daily high-dose induction therapy with interferon-alpha2b (IFN-alpha2b) in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-to-treat patient group.
  
  
  METHODS
  Seventy patients were enrolled in this study. Treatment was started with 10 MU IFN-alpha2b daily for 3 wk, followed by IFN-alpha2b 5 MU/TIW in combination with ribavirin (1 000-1 200 mg/d) for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 (IFN-alpha2b 3 MU/TIW+1 000-1 200 mg ribavirin/daily).
  
  
  RESULTS
  The dose of IFN-alpha2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response (EVR) was achieved in 60% of patients. Fifty percent of all patients achieved an end-of-treatment response (EOT) and 40% obtained a sustained viral response (SVR). Patients with no response had a significantly lower response rate than those with a former relapse (SVR 30% vs 53%; P = 0.049). Furthermore, lower response rates were observed in patients infected with genotype 1a/b than in patients with non-1-genotype (SVR 28% vs 74%; P = 0.001). As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus.
  
  
  CONCLUSIONS
  Daily high-dose induction therapy with interferon-alpha2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.
authors.affiliation: Department of Gastroenterology and Hepatology, University of Tuebingen, Otfried-Muller-Strabe 10, 72076 Tubingen, Germany. holger.hass@med.uni-tuebingen.de
authors.forename: Holger-G
authors.initials: HG
authors.lastname: Hass
authors.forename: Christian
authors.initials: C
authors.lastname: Kreysel
authors.forename: Johannes
authors.initials: J
authors.lastname: Fischinger
authors.forename: Josef
authors.initials: J
authors.lastname: Menzel
authors.forename: Stephan
authors.initials: S
authors.lastname: Kaiser
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin