Interferon/long-term lamivudine combination therapy in anti-HBe positive chronic hepatitis B patients.
BACKGROUND
Monotherapy with a single antiviral agent is insufficient in controlling hepatitis B virus infection in the majority of patients with anti-HBe positive chronic hepatitis B. Interferon/long-term lamivudine combination therapy was evaluated to determine if this strategy would improve treatment efficacy and reduce the emergence of lamivudine resistance.


METHODS
In total, 36 consecutive anti-HBe positive patients were treated with interferon (3 MU subcutaneously three times weekly) and lamivudine (100 mg orally once a day) for 12 months. After completion of the combined treatment, all patients continued to receive lamivudine monotherapy indefinitely.


RESULTS
Overall, 35 patients (97%) showed virological response at 12 months. Four patients (11%) cleared HBsAg and developed anti-HBs. During the follow-up time, after the discontinuation of interferon, of 30 +/- 12 months (range: 7-57 months), 13 patients (36%) exhibited breakthrough infection. The cumulative rates of breakthrough infection at the end of 1, 2, 3 and 4 years of treatment were 0%, 14%, 32%, and 59%, respectively.


CONCLUSIONS
Combination therapy appears to be effective and may also delay the selection of lamivudine-resistant variants. However, controlled trials are definitely warranted to clarify the potential benefits of combination antiviral treatment over monotherapy.
Nikolaidis
Nikolaos L
NL
Gastroenterology and Hepatology Section of Second Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. niknik@med.auth.gr
Giouleme
Olga I
OI
Tziomalos
Konstantinos A
KA
Saveriadis
Adamos S
AS
Grammatikos
Nikolaos
N
Doukelis
Panagiotis
P
Voutsas
Anastasios D
AD
Vassiliadis
Themistoklis
T
Patsiaoura
Kalliopi
K
Orfanou-Koumerkeridou
Eleni
E
Balaska
Aikaterini
A
Eugenidis
Nikolaos P
NP
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D019259:Lamivudine / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012008:Recurrence; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors
D000998:Antiviral Agents; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D007372:Interferons