A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. Multicenter Study Group.
BACKGROUND
We studied the effects of long-term treatment with interferon on histologic features of the liver and serum alanine aminotransferase concentrations in patients with chronic non-A, non-B hepatitis.


METHODS
Consecutive patients who met the inclusion criteria were enrolled in the study. The diagnosis of chronic non-A, non-B hepatitis was established on the basis of the liver-biopsy findings and an abnormal serum alanine aminotransferase value (greater than 1.5 times the normal value) for at least one year. All patients were treated for six months with 3 million units of interferon alfa-2b given subcutaneously three times a week and were then randomly assigned to the same treatment for an additional 12 months (group 1), a regimen of 1 million units three times a week for 12 months (group 2), or no further treatment (group 3). Patients in group 3 who had elevated serum alanine aminotransferase concentrations for three consecutive months underwent the initial regimen once again. Follow-up continued for two years after the discontinuation of treatment. Histologic improvement was defined as a decrease of at least one grade in the score for necroinflammatory activity (0, no activity; 1, mild; 2, moderate; or 3, severe) between the first liver biopsy and a biopsy performed at 18 months.


RESULTS
Of the 329 patients initially treated, 303 were randomized: 103 to group 1, 101 to group 2, and 99 to group 3. Of the 286 patients tested, 252 (88.1 percent) had antibodies to hepatitis C virus. In an intention-to-treat analysis, 46 of the patients in group 1 (44.7 percent) had normal serum alanine aminotransferase values at 18 months, as compared with 27 of the patients in group 2 (26.7 percent, P = 0.008) and 30 of those in group 3 (30.3 percent, P = 0.04). Between 19 and 42 months, 23 of the patients in group 1 (22.3 percent) continued to have normal serum alanine aminotransferase values (measured every six months), as compared with 10 of the patients in group 2 (9.9 percent, P = 0.02) and 8 of those in group 3 (8.1 percent, P = 0.005). Among the 176 patients with repeated liver biopsies at 18 months, more patients in group 1 had improved histologic-activity scores (69.6 percent) than in group 2 (47.6 percent, P = 0.02) or group 3 (38.6 percent, P < 0.001).


CONCLUSIONS
Among patients with chronic non-A, non-B hepatitis, a regimen of 3 million units of interferon alfa-2b given three times a week for 18 months produced better histologic findings and serum alanine aminotransferase values than regimens involving a lower dose or a shorter duration of treatment.
Poynard
T
T
Service d'Hépato-Gastroentérologie, Hôpital Antoine Béclère, Clamart, France.
Bedossa
P
P
Chevallier
M
M
Mathurin
P
P
Lemonnier
C
C
Trepo
C
C
Couzigou
P
P
Payen
J L
JL
Sajus
M
M
Costa
J M
JM
D000410:Alanine Transaminase / Q000378:metabolism; D002908:Chronic Disease; D002985:Clinical Protocols; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000276:immunology; D006508:Hepatitis Antibodies / Q000097:blood; D016751:Hepatitis E / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011994:Recombinant Proteins
D006508:Hepatitis Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000410:Alanine Transaminase