Genetic Variations Linked to Hepatitis B Virus Clearance in Children

It is increasingly clear that human genetic variations influence the natural history of hepatitis B virus (HBV) infection and response to treatment. However, the influence of the HLA DQA1 and DQB1 alleles on the results of interferon alpha therapy is not well defined.

As reported at the 46th ICAAC, held last week in San Francisco, Polish researchers conducted a study to examine the relationship between HLA alleles and response to interferon therapy in children with hepatitis B after treatment with conventional interferon alpha (3 MU 3 times weekly for 5-6 months). HLA alleles (26 DQA1 and 49 DQB1) were tested using high resolution DNA typing (PCR-SSP).

Patients were divided into 3 groups:

Group A (n = 46): complete sustained response, defined as HBeAg and HBV DNA clearance, normal ALT;

Group B (n = 98): HBeAg clearance, continued detectable HBV DNA, mainly normal ALT;

Group C (n = 39): non-responders.

Results

According to DQA1 alleles, an association between the frequency of 26 alleles in groups A vs B, A vs C, and A vs B+C was observed.

The comparison of groups B vs C showed a significantly higher frequency of the DQA1*0501 allele in group B (40.0%) compared with group C (11.4%) (P = 0.02).

The HLA DQB1*0502 allele was absent in group A, but was present in 16.7% of patients in group B and 10.3% of patients in group C.

The difference was statistically significant in a comparison of group A vs B (P = 0.02).

A similar result was observed when comparing group A vs B+C together (P = 0.02).

Groups B+C were characterized by significantly greater frequency of haplotype DQB1*0502-DRB1*16 compared with group A (P = 0.02).

Conclusion

The researchers concluded that DQA1*0501 carriers had a "predisposition to HBeAg clearance but not to HBV DNA elimination." Furthermore, HLA DQB1*0502 and DQB1*0502-DRB1*16 were associated with non-response to interferon alpha therapy.

Dept. of Pediatric and Infectious Diseases, Wroclaw, Poland; Inst. of Immunology and Therapy Experimentalis, Wroclaw, Poland.

10/06/06

Reference
I Kacprzak-Bergman, B Nowakowska, I Zaleska, and others. Association of HLA DQA1 and DQB1 Alleles with Response to Interferon Alpha Therapy in Children with Chronic Hepatitis B. 46th ICAAC. San Francisco, CA. September 27-30, 2006. Abstract G-862.

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