Unfavourable effects of colchicine in combination with interferon-alpha in the treatment of chronic hepatitis C.
BACKGROUND
The prognosis of chronic hepatitis depends on the progression of hepatic fibrosis.


OBJECTIVE
To investigate whether the antifibrotic drug colchicine, in combination with interferon-alpha has a role in the treatment of chronic hepatitis C.


METHODS
Sixty-five HCV-RNA positive patients with chronic hepatitis were randomized to receive interferon-alpha, 6 MU t.i.w. for 6 months followed by 3 MU t.i.w. for further 6 months, with or without the adjunct of colchicine, 1 mg o.d., 6 days a week, for 3 years. We report an interim analysis after the first 18 months.


RESULTS
Thirty-four patients received interferon-alpha and 31 received interferon-alpha and colchicine. The two groups were comparable for baseline data, including HCV-RNA levels, genotypes and histological grading/staging. Drop-outs and side-effects were similar. The proportion of patients who achieved alanine transaminase normalization or undetectable HCV-RNA at month 6 was higher in the interferon-alpha (68% and 47%, respectively) than in the interferon-alpha plus colchicine group (32% and 23%, P=0.004 and P=0. 04, respectively). End-of-treatment biochemical and virological response occurred in 41% and 29% of the interferon-alpha and 19% and 10% of the combination group, respectively (P=0.05 and P=0.05). Sustained biochemical response occurred in 26% of the interferon-alpha and 6% of the interferon-alpha plus colchicine group (P=0.03), corresponding percentages of sustained HCV-RNA loss being 21% and 3% (P=0.04).


CONCLUSIONS
The combination of colchicine and interferon-alpha worsens the effectiveness of interferon-alpha alone in HCV chronic hepatitis. These alarming findings prompted us to interrupt the trial at this stage.
Angelico
M
M
Chairs of Gastroenterology, Department of Public Health, University of Rome Tor Vergata, Italy. angelico@med.uniroma2.it
Cepparulo
M
M
Barlattani
A
A
Liuti
A
A
Gentile
S
S
Hurtova
M
M
Ombres
D
D
Guarascio
P
P
Rocchi
G
G
Angelico
F
F
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003078:Colchicine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006074:Gout Suppressants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
D000998:Antiviral Agents; D006074:Gout Suppressants; D016898:Interferon-alpha; D000410:Alanine Transaminase; D003078:Colchicine