Retreatment of chronic hepatitis B e antigen-positive patients with recombinant interferon alfa-2a. The European Concerted Action on Viral Hepatitis (EUROHEP).
Fifty-seven patients with chronic hepatitis B, hepatitis B virus (HBV) e antigen (HBeAg) and HBV DNA positivity, and aminotransferase elevation despite a previous course of any type of adequate interferon alfa (IFN-alpha) therapy were included in a multicenter prospective randomized controlled trial. The objective of the study was to compare a second course of IFN-alpha therapy (9 million units [MU] of IFN-alpha-2a, Roferon-A, thrice weekly for 6 months) versus no therapy in terms of loss of HBV DNA and HBeAg. At the end of the study, a sustained clearance of HBV DNA and HBeAg was observed in 9 of the 27 (33.3%) patients who had received retreatment with IFN-alpha compared with 3/30 (10%) patients who spontaneously cleared these markers in the untreated control group (chi2 = 4.66, P =.031; odds ratio: 4.5, 95%; confidence interval: 1.1-18.9). None of the responders lost HBsAg. Patients retreated with IFN-alpha were more likely to have biochemical remission in association with HBV clearance (5/27, 18.5%) compared with untreated patients (1/30, 3. 3%; Fisher's exact test P =.09 ). Histological improvement in the liver necroinflammatory activity was observed among sustained responders to IFN-alpha retreatment, consisting of regression of the portal and periportal inflammation and of the piecemeal necrosis; there was no change in the degree of liver fibrosis. Side effects were similar to those previously reported during IFN-alpha treatment; these were mild and reversible on IFN-alpha discontinuation. None of the baseline features were associated with response by Cox's regression analysis. In summary, viremic patients with chronic HBeAg-positive hepatitis may experience disease remission following retreatment with IFN-alpha. Thus, retreatment with IFN-alpha may be considered a therapeutic option.
Carreño
V
V
Department of Hepatology, Fundación Jiménez Díaz, Madrid, Spain. vcarreno@uni.fjd.es
Marcellin
P
P
Hadziyannis
S
S
Salmerón
J
J
Diago
M
M
Kitis
G E
GE
Vafiadis
I
I
Schalm
S W
SW
Zahm
F
F
Manzarbeitia
F
F
Jiménez
F J
FJ
Quiroga
J A
JA
D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000097:blood / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007249:Inflammation; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D011446:Prospective Studies; D011994:Recombinant Proteins; D017211:Treatment Failure
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins