EASL Clinical Practice Guidelines

Predictors of response

Several baseline and on-treatment predictors of response have been identified for children treated with IFN-α and lamivudine, whereas no data from pediatric studies exists for other NA.

In HBeAg-positive patients, likelihood of response to IFN-α is associated with low HBV DNA levels and elevated ALT levels (more than twice the ULN) before treatment, younger age and female sex (A1) [[59], [91], [92], [93]]. Elevated ALT levels at baseline are associated with higher long-term seroconversion rate after treatment (B2) [74]. Early response to IFN-α is more likely to lead to HBsAg loss than late or no-response (C2) [73]. A better response to IFN-α has been shown in adults for viral genotypes A and B, compared to D and C [[15], [94], [95], [96]]. No pediatric studies have yet investigated the role of genotype on response to antiviral therapy, and genotype determination before treatment is not currently recommended(C2), until the role of the viral genotype in assigning children to treatment and in predicting response has been clarified. A decrease of the HBsAg serum levels after the first 3 months of treatment predicts SVR and HBsAg loss in adults treated with pegylated IFN (PegIFN), but no data are available in children treated with IFN-α [[97], [98], [99]].

The likelihood to respond to lamivudine is greater in children with higher ALT levels (at least twice the ULN), and high histologic activity index at baseline (A1) [[60], [75]]. In adult patients, the same parameters, as well as low HBV DNA levels (HBV DNA <2 × 108 IU/ml), were predictive of response to all NA (A1) [[85], [90], [100], [101]]. No significant difference in response to NA was found among different genotypes (A1) [[102], [103]]. In adults, VR at 24 weeks during treatment with lamivudine or telbivudine (and 48 weeks during treatment with adefovir) is associated with a higher chance of HBeAg seroconversion, maintained virological response, and lower incidence of resistance (B1) [[90], [104], [105], [106]]. The decline of HBsAg serum levels during NA treatment predicts HBeAg seroconversion or HBsAg loss (C2) [[107], [108], [109]].