Predictors of virologic response to Lamivudine treatment in children with chronic hepatitis B infection.
BACKGROUND
Some children with chronic hepatitis B develop advanced liver disease. Lamivudine, an oral nucleoside, is a therapeutic option. A recent large, multicenter study demonstrated that lamivudine was superior to placebo in eliciting loss of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA from serum in children (2 to 17 years) treated for 52 weeks.


OBJECTIVE
To identify pretreatment factors that predict the likelihood of response to lamivudine in children with chronic hepatitis B infection.


METHODS
Data from the multicenter trial in 297 children (191 lamivudine, 96 placebo) were analyzed for the effects of baseline factors on the likelihood of responses. These responses included virologic response, defined as loss of HBeAg and HBV DNA, and HBeAg seroconversion, defined as loss of HBeAg and development of antibody to HBeAg. Univariate and multivariate analyses examined the effects of lamivudine treatment, age, gender, race, body weight, body mass index, previous interferon treatment and baseline alanine aminotransferase (ALT), histologic activity index (HAI) score and HBV DNA on the virologic responses.


RESULTS
In the univariate analysis higher baseline ALT, higher HAI score and lower HBV DNA level predicted a greater likelihood of virologic responses to lamivudine. In the multivariate model only baseline ALT and HAI score were predictive of responses. There was no effect of age or ethnicity on response.


CONCLUSIONS
Children with higher pretreatment ALT and HAI scores are most likely to respond to lamivudine. Age, ethnicity and other factors do not significantly influence the frequency of virologic responses in children with chronic hepatitis B infection.
Hom
Xenia
X
Division of Gastroenterology, Children's Hospital Boston, Boston, MA, USA.
Little
Nancy R
NR
Gardner
Stephen D
SD
Jonas
Maureen M
MM
D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood*; D004311:Double-Blind Method; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology*; D011237:Predictive Value of Tests; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D000410:Alanine Transaminase