Retreatment with interferon-alpha and ribavirin in primary interferon-alpha non-responders with chronic hepatitis C.
OBJECTIVE
Combination therapy with interferon-alpha (IFN-alpha) plus ribavirin is more efficacious than IFN-alpha monotherapy in previously untreated patients with chronic hepatitis C and patients with IFN-alpha relapse. Only limited data are available in IFN-alpha non-responders. In a multicenter trial we therefore evaluated the efficacy of combination therapy in IFN-alpha-resistant chronic hepatitis C.


METHODS
Eighty-two patients (mean age 46.8 years, 54 males, 28 females) with chronic hepatitis C were treated with IFN-alpha-2a (3 x 6 MIU/week) and ribavirin (14 mg/kg daily) for 12 weeks. Thereafter, treatment was continued only in virological responders (undetectable serum HCV RNA at week 12) with an IFN-alpha dose of 3 x 3 MIU/week and without ribavirin for a further 9 months. The primary study endpoint was an undetectable HCV RNA by RT-PCR at the end of the 24-week follow-up period.


RESULTS
After 12 weeks of combination therapy, an initial virological response was observed in 29 of 82 (35.4%) patients. Due to a high breakthrough rate after IFN-alpha dose reduction and ribavirin discontinuation, an end-of-treatment response was only achieved in 12 of 82 (14.6%) patients. After the follow-up period, a sustained virological response was observed in 8 of 82 (9.8%) patients. Infection with HCV genotype 3 was the only pretreatment parameter, which could predict a sustained response (HCV-1, 5%; HCV-3, 57.1%; p < 0.001).


CONCLUSIONS
Despite a high initial response rate of 35.4%, sustained viral clearance was achieved only in 9.8% of the retreated primary IFN-alpha non-responders. Higher IFN-alpha induction and maintenance dose, as well as prolonged ribavirin treatment may possibly increase the virological response rates in non-responders, particularly in those infected by HCV-1.
Teuber
G
G
Medizinische Klinik II, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt, Deutschland.
Berg
T
T
Hoffmann
R M
RM
Leifeld
L
L
Lafrenz
M
M
Spengler
U
U
Pape
G R
GR
Hopf
U
U
Zeuzem
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001707:Biopsy, Needle; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011336:Probability; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis*; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure; D016896:Treatment Outcome
D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin