[A randomized controlled study on factors influencing the curative effect of sequential combined interferon and lamivudine therapy in children with immune-tolerant phase chronic hepatitis B].

Objective: To investigate the curative effect of antiviral therapy and related factors influencing the curative affect in children with immune-tolerant phase chronic hepatitis B. Methods: From May 2014 to April 2015, 46 children with chronic hepatitis B, aged 1 to 16 years with immune-tolerant phase were enrolled as the treatment group. All cases in the treated group either received interferon alpha (3-5 MIU/m(2), once daily) in lamivudine combination (if HBV DNA decreased < 2 log(10)) or repeatedly received interferon-alpha alone (if HBV DNA decreased >2 log(10)) for 12 weeks. Interferon was discontinued at 72 weeks and followed-up period was continued with lamivudine for 24 weeks. At the same time, data of 23 cases of untreated children with immune-tolerant phase chronic hepatitis B were collected as the control group. The treatment group and the control group were divided into two age groups: 1-7 years old and 7-15 years old. Data measurements were compared using t-test, analysis of variance and single factor analysis methods, and the count data were analyzed by χ (2) test. Multiple logistic regression analysis was used to analyze the effects of different factors on response. Results: (1) There were 22 cases aged 1-7 years in the treatment group (47.8%) and 12 cases aged 1-7 years in the control group (52.2%). The cases of mother-to-child transmission (MTCT) in treatment and control group were 34 (73.9%) and 17 (73.9%), while children with normal baseline ALT in the treatment and control group were 18 (39.1%) and 10 (43.5%). (2) At the end of follow-up, 15 cases in the treatment group (32.6%) had HBeAg serological conversion. Among them, nine (19.6%) cases had HBsAg clearance or HB-Ag seroconversion with anti-HBs, and one (2.2%) case had HBsAg clearance, but both HBeAg and anti-HBe were positive. In the control group, one case had HBV DNA lower than the lower limit of detection level, and one case had HBeAg seroconversion without HBsAg clearance. (3) At the end of follow-up, the seroconversion rates of HBeAg in patients aged 1 to 7 years and patients aged 7 to 15 years were 45.5% and 20.8%, respectively (P = 0.078) and the clearance rates of HBsAg were 36.4% and 8.3% (P = 0.023). The serum conversion rates of normal and abnormal baseline alanine aminotransferase levels were 5.6% and 50.0% (P = 0.005), and the clearance rates of HBsAg were 5.6% and 32.1% (P = 0.077), respectively. There was no statistically significant difference in gender, mother-to-child transmission, HBV DNA genotyping and baseline HBsAg level in antiviral efficacy among children (P > 0.05). (4) HBsAg and HBeAg clearance occurred in 100% of patients at the end of follow-up who had HBsAg < 3 000 IU/ml at 24 weeks of treatment. (5) Multivariate logistic regression analysis showed that serum HBeAg conversion rate had relation with non-MTCT transmission and abnormal baseline alanine aminotransferase. Furthermore, HBsAg clearance rate was associated with the age of children. Conclusion: Sequential combination of interferon and lamivudine with a prolonged course can improve the HBV DNA negative conversion rate, HBeAg seroconversion rate, HBsAg loss rate and mild ALT abnormalities at baseline in children under the age of 7 years with immune-tolerant phase chronic hepatitis B.