Prolonged treatment (2 years) with different doses (3 versus 6 MU) of interferon alpha-2b for chronic hepatitis type C. Results of a multicenter randomized trial.
OBJECTIVE
To examine the effect of prolonged treatment with different doses of interferon alpha-2b on the relapse rate in patients with chronic hepatitis C.


METHODS
One hundred and seventy-one patients with non-cirrhotic chronic hepatitis C were enrolled in an Italian multicenter trial. All patients were treated for 3 months with 3,000,000 Units (3 MU) of interferon alpha-2b given subcutaneously three times a week (t.i.w.). Patients with abnormal alanine aminotransferase (ALT) values were given 6 MU of interferon for an additional 3 months. If ALT remained persistently abnormal, therapy was then suspended. If ALT levels were normal, therapy was continued (6 MU t.i.w.) for an additional 18 months (total=2 years). Patients with normal ALT were randomly assigned to two groups, one receiving 3 MU and the other receiving 6 MU t.i.w. for an additional 21 months (total=2 years). Follow-up continued for 2 years after therapy withdrawal.


RESULTS
Seven patients stopped treatment during the first 3 months. Of the remaining 164 patients, 76 (46%) showed abnormal ALT levels after 3 months of therapy: 11 of these (14%) normalized ALT values when given 6 MU and a sustained response was maintained in eight during the follow-up. Overall, 54 and 34 patients were allocated respectively to the groups receiving the 3 MU and 6 MU long-term treatment. At the end of therapy, 35/54 patients of the group 3 MU and 21/34 patients of the group 6 MU showed normal ALT levels (65% vs 62%, p=N.S.). After 2 years of follow-up, 24/35 (69%) patients of the group 3 MU and 16/21 (76%) of the group 6 MU were still in remission (p=N.S.). In an intention-to-treat analysis, 48/171 (28%) patients showed a long-term response (normal ALT values, HCV-RNA negative). About 65% of the sustained responders showed low baseline viremia compared with 33% of non-responders (p=0.005) while genotype 1b was more frequently found among non-responders than in long-term responders (84% vs 25%, p=0.0001).


CONCLUSIONS
About 14% of patients who do not respond to a 3-month course of 3 MU of interferon normalize ALT levels when given 6 MU. In prolonged treatment, there is no significant difference between 3 and 6 MU in inducing a sustained response. Patients with low baseline viremia and genotype 2a respond significantly better to prolonged interferon therapy than highly viremic patients with genotype 1b.
Saracco
G
G
Dipartimento di Gastroenterologia, Ospedale Molinette, Turin, Italy.
Borghesio
E
E
Mesina
P
P
Solinas
A
A
Spezia
C
C
Macor
F
F
Gallo
V
V
Chiandussi
L
L
Donada
C
C
Donadon
V
V
Spirito
F
F
Mangia
A
A
Andriulli
A
A
Verme
G
G
Rizzetto
M
M
D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000473:pathology / Q000628:therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014766:Viremia / Q000628:therapy / Q000821:virology
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins