Long-term alpha interferon and lamivudine combination therapy in non-responder patients with anti-HBe-positive chronic hepatitis B: results of an open, controlled trial.
OBJECTIVE
To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudine in non-responsive patients with anti-HBe-positive chronic hepatitis B.


METHODS
34 patients received combination treatment (1 month lamivudine, 12 month lamivudine+interferon, 6 month lamivudine), 24 received lamivudine (12 months), 24 received interferon (12 months). Interferon was administered at 6 MU tiw and lamivudine at 100 mg orally once daily. Patients were followed up for 6 months after treatment.


RESULTS
At the end of treatment, HBV DNA negativity rates were 88 % with lamivudine+interferon, 99 % with lamivudine and 55 % with interferon, (P=0.004, combination therapy vs. interferon, and P=0.001 lamivudine vs. interferon), and serum transaminase normalization rates were 84 %, 91 % and 53 % (P=0.01 combination therapy vs. interferon, and P=0.012 lamivudine vs. interferon). Six months later, HBV DNA negativity rates were 44 % with lamivudine+interferon, 33 % with lamivudine and 25 % with interferon, and serum transaminase normalization rates were 61 %, 42 % and 45 %, respectively, without statistical significance. No YMDD variants were observed with lamivudine+interferon (vs. 12 % with lamivudine). The combination therapy appeared to be safe.


CONCLUSIONS
Although viral clearance and transaminase normalization are slower with long-term lamivudine+interferon than that with lamivudine alone, the combination regimen seems to provide more lasting benefits and to protect against the appearance of YMDD variants. Studies with other regimens regarding sequence and duration are needed.
Jaboli
M Francesca
MF
Department of Internal Medicine and Gastroenterology, University of Bologna, Italy.
Fabbri
Carlo
C
Liva
Stefania
S
Azzaroli
Francesco
F
Nigro
Giovanni
G
Giovanelli
Silvia
S
Ferrara
Francesco
F
Miracolo
Anna
A
Marchetto
Sabrina
S
Montagnani
Marco
M
Colecchia
Antonio
A
Festi
Davide
D
Reggiani
Letizia Bacchi
LB
Roda
Enrico
E
Mazzella
Giuseppe
G
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome
D000998:Antiviral Agents; D016898:Interferon-alpha; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine