Combination therapy for children with chronic hepatitis B virus infection.
OBJECTIVE
To compare the therapeutic efficacy of two different interferon (INF)-alpha and lamivudine (LAM) combination therapy regimens in childhood chronic hepatitis B (CHB) infections.


METHODS
Thirty-two children with CHB infection were prospectively evaluated in two random groups. In the first group, patients received INF-alpha 10 MU/m2 and LAM 4 mg/kg (max 100 mg) simultaneously for 6 months, and then LAM alone was continued for 6 months. In the second group, LAM was started alone for the first 2 months, then INF-alpha added to LAM for 6 months, after which INF-alpha was stopped, and LAM alone was continued for 4 months. The same doses of LAM and INF-alpha were used in both groups.


RESULTS
In the first group, the mean values of alanine aminotransferase (ALT) were 125 +/- 100 IU/L and 28 +/- 8 IU/L at the beginning of the treatment and at the end of the 12 months, respectively (P < 0.05). At the end of 6 months of the follow-up period, the mean ALT value was 36 +/- 37 IU/L. In group 2, mean ALT values were 111 +/- 63 IU/L, 35 +/- 2 IU/L and 34 +/- 2 IU/L initially, at the end of 12 months and at the end of 6 months of follow up, respectively (P < 0.05). At the end of therapy, the ratios of hepatitis B early antigen (HBeAg) clearance and antibody to HBeAg (anti-HBe) seroconversion were 65% and 47% in group 1 and 60% and 40% in group 2, respectively (P > 0.05). After 6 months from completion of therapy, rates of seroconversion to anti-HBe were found to be 64% and 47% in group 1, and 53% and 46% in group 2, respectively (P > 0.05). Hepatitis B virus (HBV) DNA was detectable by polymerase chain reaction in only one patient in group 1 at the end of therapy and 6 months after termination of therapy. Clearance of HBV DNA in group 2 was observed in all but one patient at the end of the therapy. However, two patients relapsed within 6 months of cessation of therapy. Complete response occurred in 47% and 40% of patients at the end of the therapy in group 1 and 2, respectively (P > 0.05). These ratios were changed to 47% and 46%, respectively, 6 months after discontinuation of drugs (P > 0.05).


CONCLUSIONS
Comparison of our two different combination regimens disclosed similar results in the normalization of ALT, clearance of HBeAg and HBV DNA and seroconversion to anti-HBe. However, the most beneficial combination of LAM and INF-alpha treatment modalities needs to be further investigated.
Department of Pediatrics, Dicle University Medical School, Diyarbakir, Turkey. bdikici@dicle.edu.tr
Bunyamin
B
Dikici
Mehmet
M
Bosnak
Vuslat
V
Bosnak
Abdullah
A
Dagli
Aydin
A
Ece
Rasit Vural
RV
Yagci
Kenan
K
Haspolat
D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis; D004359:Drug Therapy, Combination; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase