The Therapeutic Effect of Interferon-alpha Treatment in Children with Chronic Hepatitis B

Jeong, Il Sang; Chung, Ki Sup

Abstract

PURPOSE
The prevalance rate of chronic hepatitis B viral infection in children is high in our contry. We performed a prospective study to evaluate the effectiveness of and the factors predictive of response to interferon-alpha therapy in children with chronic hepatitis B.
METHODS
Thirty-two children with chronic hepatitis B werew admitted to the Department of Pediatrics, Yonsei University College of Medicine from Oct. 1992 to Apr. 1994, and liver biopsies were performed. They recieved interferon-alpha (Intermax-alpha: 3 million IU intramuscularly three times a week) for from 4 to 6 months and were followed for 19+/-7.5 months after treatment. The control group comprised forty children with chronic hepatitis B who had conservative or no treatment. The therapeutic effectiveness of IFN-alpha was evaluated, and factors predictive of response to treatment were analyzed.
RESULTS
1) Thirty two children in the treatment group comprised 22 males and 10 females. The mean age was 11.7+/-3.5 years at entry. The pathologic types were chronic lobular hepatitis in 4, chronic persistant hepatitis in 12 and chronic active hepatitis in 16 cases. The mean age of 40 children in the control group was 8.2+/-4.4 years. There were no differences in the clinical and laboratory data between the two group. 2) The serum ALT and AST levels normalized in 29 (91%) of 32 treated cases and 33 (88%) of 40 controls. The normalization of serum aminotransferases in control group, however, was thought to be meaningful because most controls were in healthy chronic carrier state with normal aminotransferases levels. The serum HBV-DNA was cleared in 25 (78%) of 32 treated cases and 7 (41%) of 40 controls, which showed statistically significant difference (P<0.005) between two groups. HBeAg was cleared in 24 (75%) of the treated cases and 10 (25%) of 40 controls (P<0.05). The positive seroconversion of anti-HBe was noted in 18 (56%) of 32 treated cases and 7 (18%) of 40 controls (P<0.05). 3) Normalization rate of AST and ALT levels, the clearance rate of HBV-DNA andHBeAg, and the seropositive rate to anti-HBe were 100%, 50%, 75% and 50% in CLH; 83%, 75%, 58% and 42% in CPH; 94%, 88%, 88% and 69% in CAH, respectively. 4) Children with higher pretreatment peak ALT level were more likely to clear HBeAg and HBV-DNA. The clearance of HBeAg and HBV-DNA were 6 (55%) and 5 (45%) of 11 children with pretreatment peak ALT level of less than 100IU/L; 6 (75%) and 7 (88%) of 8 children with pretreatment peak ALT level of 100-200IU/L; 12 (92%) and 13 (100%) of 13 children with pretreatment peak ALT level of greater than 200IU/L. 5) Children with lower pretreatment HBV-DNA level were more likely to clear HBeAg and HBV-DNA. The clearance of HBeAg and HBV-DNA were 13 (72%) and 14 (78%) of 18 children with pretreatment HBV-DNA level less than 100pg/ml; 2 (40%) and 2 (40%) of 5 children with pretreatment HBV-DNA level greater than 100pg/ml. 6) Children with higher post-treatment peak ALT level were more likely to clear HBeAg and HBV-DNA. The clearance of HBeAg and HBV-DNA were 8 (73%) and 7 (64%) of 11 children with posttreatment peak ALT level less than 100IU/L; 9 (69%) and 10 (77%) of 13 children with post-treatment peak ALT level of 100-200IU/L; 7 (88%) and 8 (100%) of 8 children with post-treatment peak ALT level greater than 200IU/L. 7) Normalization of serum ALT and AST level took 7.1+/-6.8 months. The clearance of HBV-DNA and HBeAg took 12.9+/-8.3 and 10.1+/-7.3 months, respectively. positive seroconversion to antiHBe was obserbed at 10.6+/-6.3 months after IFN-alpha treatment.
CONCLUSION
These results suggest that interferon-alpha therapy can induce an increased clearance of HBV-DNA and HBeAg with an increased positive seroconversion to anti-HBe in children with chronic type B hepatitis. Factors that may help in in identifying those children with a better chance of responding, were higher pre- and post-treatment peak ALT levels and lower pretreatment peak HBV-DNA levels.