Statistical models for predicting response to interferon-alpha and spontaneous seroconversion in children with chronic hepatitis B.
To develop prognostic models for identifying children with hepatitis B who are likely to respond to interferon-alpha (IFN-alpha) or to spontaneously seroconvert, we evaluated results of a multinational controlled trial comprising 70 children with chronic hepatitis B who received IFN-alpha and 74 children who did not receive therapy. Prognostic models were developed using SMILES (similarity of least squares), which is a data analysis network that incorporates multidimensional relationships in the clinical data of complex diseases. Commonly collected clinical data included age, gender, serum aminotransferase (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and hepatitis B virus (HBV) DNA levels, and IFN-alpha dose. Additional data included pretreatment directional information (e.g. increases or decreases in serum aminotransferase and HBV DNA levels), liver biopsy results, race and transmission mode. Using data available prior to initiation of treatment, the SMILES models achieved prospective predictions of 89% for responders, 96% for non-responders, 100% for seroconverters and 93% for non-seroconverters. Although not predictive by themselves, the variables that had the greatest impact on predictions for IFN-alpha response were HBV DNA pretreatment direction, baseline HBV DNA, IFN-alpha dose and gender. The variables that had the greatest impact on predictions for spontaneous seroconversion were ALT pretreatment direction, baseline HBV DNA level, age and AST pretreatment direction. Therefore, these models may be useful in determining, in children with hepatitis B, the likelihood of response to IFN-alpha and spontaneous seroconversion.
Comanor
L
L
Bayer Diagnostics (formerly Chiron Diagnostics), Emeryville, CA 94301, USA.
Minor
J
J
Conjeevaram
H S
HS
Roberts
E A
EA
Alvarez
F
F
Bern
E M
EM
Goyens
P
P
Rosenthal
P
P
Lachaux
A
A
Shelton
M
M
Sarles
J
J
Sokal
E M
EM
D000293:Adolescent; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D019694:Hepatitis B, Chronic / Q000628:therapy*; D006801:Humans; D007223:Infant; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D015233:Models, Statistical; D012984:Software
D000998:Antiviral Agents; D016898:Interferon-alpha