Retreatment of patients with chronic hepatitis C not responding to interferon/ribavirin combination therapy with daily interferon plus ribavirin plus amantadine.
There is currently no accepted therapeutic regimen for patients with chronic hepatitis C who failed to respond to standard combination treatment with interferon-alpha plus ribavirin. We investigated triple combination treatment with induction dosing of interferon-alpha plus ribavirin plus amantadine in these difficult-to-treat patients. Nonresponders (n = 67), breakthroughs (n = 16) and relapsers (n = 19) to previous interferon/ribavirin combination treatment of at least 6 months were included. For the first 16 weeks, patients received interferon-alpha2a 6 MU daily, ribavirin 800-1200 mg/d, and amantadine 200 mg/d. In cases of undetectable HCV RNA at week 12, treatment was continued with interferon-alpha2a 6 MU every other day and the same doses of ribavirin and amantadine until week 48. In cases of HCV RNA positivity at week 12, treatment was stopped. A total of 102 patients were enrolled (80%: genotype 1, 19%: cirrhosis). HCV RNA was negative in 35/102 patients (34%) at week 12 and in 27/ 102 patients (26%) at the end of treatment. Virological response was sustained in 15/102 patients (15%). On-treatment virological response was higher in previous relapsers/breakthroughs than in previous nonresponders (week 12: 49% vs. 27%, p < 0.05; week 48: 46% vs. 16%, p < 0.01) but no such difference was found for sustained virological response (20% vs. 12%, NS). In conclusion, triple combination treatment with daily interferon-alpha plus ribavirin plus amantadine for 3 months can induce virological response in a considerable number of nonresponders/relapsers to previous dual combination treatment, but the sustained virological response rate remains low.
Department of Internal Medicine, Gastroenterology and Hepatology, Karl-Franzens University, Graz, Austria. rudolf.stauber@meduni-graz.at
Rudolf E
RE
Stauber
Harald
H
Hofer
Franz
F
Hackl
Kurt
K
Schütze
Christian
C
Datz
Karin
K
Hegenbarth
Wolfgang
W
Jessner
Petra
P
Steindl-Munda
Ferenci
F
Peter
D000328:Adult; D000368:Aged; D000547:Amantadine / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage; D001317:Austria / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004361:Drug Tolerance; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage*; D055502:Secondary Prevention; D017211:Treatment Failure; D016896:Treatment Outcome
D000998:Antiviral Agents; D004338:Drug Combinations; D016898:Interferon-alpha; D012254:Ribavirin; D000547:Amantadine