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FP13-01. Effect of Host Interleukin-10 Genotypes on HBV Precore /Core Gene Mutation and Onset of Spontaneous HBeAg Seroconversion. Jia-Feng Wu, Yen-Hsuan Ni, Huey-Ling Chen, Hong-Yuan Hsu, Mei-Hwei Chang Department of Pediatrics, National Taiwan University Hospital. Background.
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FP13-01 Effect of Host Interleukin-10 Genotypes on HBV Precore/Core Gene Mutation and Onset of Spontaneous HBeAgSeroconversion Jia-Feng Wu, Yen-Hsuan Ni, Huey-Ling Chen, Hong-Yuan Hsu, Mei-Hwei Chang Department of Pediatrics, National Taiwan University Hospital
Background ♠ HBeAg seroconversion is considered as an important indicator of subsidence of disease activity and decrease of active viral replication. Hepatology 1986; 6: 167-72 ♠ Persistent HBeAg after the 3rd to 4th decade of life associated with HBV related liver cirrhosis and HCC. N Engl J Med 2002; 347: 168-74. J Virol Hepat 2007; 14: 147-152 ♠ Our previous work demonstrated G/G genotype at -1082 of IL-10 gene promoter predict higher serum IL-10 levels and earlier HBeAg seroconversion. Gastroenterology 2010; 138: 165-172
Changes of Virus during Seroconversion • HBV precore/core gene mutation occurred in the course of HBeAg seroconversion. • The mutations of precore/core gene may alter the structure and stability of HBV nucleocapsid, and pg RNA packaging. • Precore / Core protein C-terminus mutations are also reported to alter the biosynthesis, transportation and secretion of HBeAg. J Virol 1998;273:18594-18598. Gastroenterology 2007;133:951-958. Virology 2009;387:364-372.
Hypothesis Host IL-10 genotypes associate with different HBV precore/core gene mutation patterns during spontaneous HBeAg seroconversion.
Methods • 21 chronic HBV infected children followed for more than 10 years with spontaneous HBeAg seroconversion were included as the seroconverter group. • 9 chronic HBV infected children with similar follow-up without HBeAg seroconversion as non-seroconverter group. • All of them are 1. Infected by genotype B HBV 2. HBeAg-positive with normal ALT at first visit 3. With peak ALT > 80 IU/L during the follow-up. 3. With chronic HBsAg carrier mother 4. No antiviral treatment
Methods • Serum samples at tolerance phase (HBeAg[+], anti-HBe[-], ALT <40 IU/L) and inflammatory phase (first available serum at ALT>80 IU/L, HBeAg[+]) were subjected to the HBV precore/core gene mutation analysis after cloning and viral load determination.
Methods • IL-10 -1082 G/A (rs1800896) polymorphism was determined in all subjects by direct sequencing after PCR amplification. Forward primer: 5’-AACTGGCTCTCCTTACTTTC-3’ Reverse primer: 5’-ATAGGAGGTCCCTTACTTTCCTC-3’
Results Tolerance phase
Results Inflammatory phase –HBeAg(+) & ALT>80 IU/L
Results Inflammatory phase –HBeAg(+) & ALT>80 IU/L Precore/core gene mutation patterns are different between HBeAg seroconverters and non-seroconverters at the inflammatory phase
Results HBeAg Epitopes Percentage of Delta epitope mutants correlated with the G1896A mutant (r=0.44, P=0.02) at inflammatory phase. Percentage of Delta epitope mutants correlated lower HBV viral load at inflammatory phase (r=-0.47, P=0.01).
Results Host Factors vs. Viral Changes at Inflammatory phase
Discussions • HBeAg seroconverters carry higher G1896A, G2304A, HBeAg beta and delta epitope mutants than HBeAg non-converters at the inflammatory phase. • G/G genotype carriers at the IL-10 -1082 polymorphism site associated with higher delta epitope mutation than the A allele carriers at the inflammatory phase. • Higher delta epitope mutation associated with lower HBV viral load at inflammatory phase (γ, -0.47; P, 0.01).
Conclusions • Different host immune factors (IL-10) associated with different HBV mutation patterns and HBV viral load change during spontaneous HBeAg seroconversion.
