Response to Lamivudine Treatment in Children with Chronic Hepatitis B Virus Infection

Abstract

Despite the recent approval of lamivudine for the treatment of children with chronic hepatitis B virus (HBV) infection, there is insufficient information on the kinetics of HBV clearance and the factors that predict a favorable treatment response to lamivudine in this population. In a small retrospective study of 16 HBV-infected children treated with lamivudine, we examined changes in virus load and other factors associated with hepatitis B e antigen (HBeAg) clearance. High pretherapy alanine aminotransferase level, low serum HBV DNA load, and age at the start of treatment were independently associated with HBeAg clearance. HBeAg clearance was also associated with the achievement of specific levels of virus suppression, and failure to achieve those levels was associated with the development of lamivudine resistance. Additional studies are necessary to provide better indications and guidelines for the treatment of children with chronic HBV infection.

Lamivudine treatment in maternally transmitted chronic hepatitis B virus infection patients

“…The above‐mentioned background information requires us to focus the treatment in patients acquiring HBV infection through maternal transmission. Our data suggest lamivudine did not achieve a better response rate in the treatment group as compared with the control group and some previous pediatric studies 10,19 . Spontaneous HBeAg seroconversion of maternally transmitted carriers commonly occurs between the ages of 15 and 30 years.…”

Management of chronic hepatitis B in children: An unresolved issue

“…Mutations conferring resistance to lamivudine occur particularly in the highly conserved tyrosine‐methionine‐aspartic acid‐aspartic acid (YMDD) motif of the catalytic domain (C domain) of the polymerase. Smaller studies of LAM treatment in children have confirmed both the efficacy in reducing serum HBV‐DNA and the high mutation rate . Several authors have recommended continuing therapy for at least 6 months after HBeAg seroconversion or until virological breakthrough occurs, but the optimal treatment duration remains unknown.…”

Lamivudine resistance in children with chronic hepatitis B

“…Jonas et al [9] determined a relapse rate of 17.5% in a placebo controlled LAM trial in children. Hagmann et al [10] found relapse rate of 25% after cessation of LAM treatment. It is likely that duration of LAM treatment would be a culprit for the variations in relapse rates.…”

“…Interestingly, YMDD mutation rate of this study was extremely higher than other studies. Hagmann et al [10] reported development of clinical resistance to LAM in 3 children (19%) in the first year of therapy. Furthermore, in this study, frequency of drug resistance is found to be low in children with high HBV-DNA suppression level.…”

“…Jonas et al [9] LAM 52 wk 26 18 19 Hagmann et al [10] LAM 12 6 mo 50 25 19 Sokal et al [15] LAM 24 mo 25 11 49 36 mo 35 0 64 Hartman et al [16] LAM 12 6 mo 18 0 65 Hong et al [5] LAM 12 mo 60.5 NA 25.9 Lee et al [17] LAM 12 mo 60 0 27 Ni et al [18] LAM 12 mo 38 0 34 Akman et al [19] LAM 32.3 ± 8.3 mo 20.8 NA 58.4 Choe et al [3] LAM 12 6 mo 65 4 10 3 23 4 Liberek et al [20] LAM 12 mo 27.1 NA 3.38 Koh et al [21] LAM 12 6 mo 42 3.3 10 Kansu et al [8] LAM + IFN 6 m IFN 60.2 1 6.8 1 17.9 1 24 mo LAM 39.4 2 0 2 24.6 2 Ozgenç et al [29] LAM + IFN 6 mo IFN 15.6 3 6.8 3 13.3 3 12-36 mo 5.6 4 69.4 4 LAM 0 5 82.4 5 Dikici et al [32] LAM + IFN 6 mo IFN 37 3.7 3.3 12 mo LAM Kuloğlu et al [33] LAM + IFN 6 mo IFN 34.2 NA 65.8 12 6 mo LAM Saltik-Temizel et al [34] LAM …”