Lamivudine vs lamivudine and interferon combination treatment of HBeAg(-) chronic hepatitis B.
To determine whether combination treatment of HBeAg(-) chronic hepatitis B is beneficial we studied 78 patients with HBeAg(-), HBV DNA-positive chronic hepatitis B who were randomized to lamivudine, 100 mg, qd, for 12 months or lamivudine-interferon (9 MU, t.i.w.) in combination. In the combination arm, 2 months of lamivudine treatment preceded 10 months of combination treatment. Biochemical, virologic and histologic responses were assessed at the end of treatment, after six and a median 27 months of drug-free follow-up (short- and long-term follow-up, respectively). Virologic response was defined as undetectable HBV DNA with a hybridization assay and biochemical response as normal alanine aminotransferase (ALT). Change in HBV DNA was also assessed by real-time polymerase chain reaction (PCR). Presence of YMDD mutants at the end of treatment was investigated with a line probe assay. Both treatment regimes led to a median 2 log decline in HBV DNA levels. Virologic end of treatment responses were 90 and 92% with mono- and combination treatment, respectively. Corresponding virologic responses at short- and long-term follow-up were 59 and 54%, and 27 and 25%, respectively. Patients having a baseline HBV DNA value > or =200 pg/mL were more likely to relapse within 6 months off therapy than those patients with a baseline HBV DNA level <200 pg/mL (P = 0.041). YMDD mutants were observed in 53% of patients receiving lamivudine compared with 24% of patients receiving the combination regime (P = 0.017). In conclusion, efficacy of combination treatment is similar to lamivudine monotherapy. However, combination treatment decreases the development of YMDD mutant strains compared with lamivudine monotherapy.
Yurdaydin
C
C
Department of Gastroenterology, Pathology and the Hepatology Institute, University of Ankara Medical School, Ankara, Turkey. cihan.yurdaydin@dialup.ankara.edu.tr
Bozkaya
H
H
Cetinkaya
H
H
Sahin
T
T
Karaoğuz
D
D
Törüner
M
M
Erkan
O
O
Heper
A O
AO
Erden
E
E
Bozdayi
A M
AM
Uzunalimoğlu
O
O
D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000008:administration & dosage*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011336:Probability; D011994:Recombinant Proteins; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine