Korean J Pediatr Gastroenterol Nutr.  2011 Sep;14(3):279-285. 10.5223/kjpgn.2011.14.3.279.

Mutations in Hepatitis B Virus Precore, Core Promoter, and "a" Determinant in Children with Chronic Hepatitis B Virus Infection

• Lee SS
• Chang JY
• Seo JK

• KMID: 2276887
• DOI: http://doi.org/10.5223/kjpgn.2011.14.3.279

Abstract

PURPOSE
The aim of this study was to determine the prevalence, types of variants, and clinical significance of mutations in precore, core promoter, and "a" determinant mutations in children with chronic hepatitis B virus infection.
METHODS
Thirty-one patients with chronic hepatitis B virus infection who visited Seoul National University Children's Hospital in Korea between 2004 and 2005 were enrolled in this study. Serum HBV DNA was amplified by polymerase chain reaction (PCR) and the precore/core promoter and "a" determinant sequences were determined.
RESULTS
Precore mutations were found in 11 of 27 patients (40.7%), and appeared more frequently in the HBeAg-negative group (p<0.05) compared to the HBeAg-positive group. G1896A was detected most frequently (81.8%). BCP mutations were found in 15 of 27 patients (55.6%) and the TA mutation (A1762T/G1764A) was the most common (86.7%). Mutations in the "a" determinant region were detected in 8 of 28 patients (28.6%), and amino acid changes were detected in 6 of 28 patients (21.4%). Of these mutations, substitutions at amino acid position 126 were found most frequently.
CONCLUSION
In children with chronic hepatitis B virus infection, the most common mutations were G1896A in the precore region and TA mutation(A1762T/G1764A) in the core promoter region. Substitutions at amino acid position 126 was the most common mutation in the "a" determinant. Precore mutants were found to be significantly higher in HBeAg-negative patients. The high prevalence of mutations in the "a" determinant and low frequency of G145R were characteristic features. These mutations were not significantly associated with other clinical features except for high aminotransferase concentration in the core promoter variant group.

Keyword

Hepatitis B virus; Precore; Core promoter; "a" determinant; Child

MeSH Terms

Child
DNA
Hepatitis
Hepatitis B
Hepatitis B virus
Hepatitis B, Chronic
Hepatitis, Chronic
Humans
Korea
Polymerase Chain Reaction
Prevalence
Promoter Regions, Genetic
Viruses
DNA

Reference

1. Lin CL, Kao JH. The clinical implications of hepatitis B virus genotype: Recent advances. J Gastroenterol Hepatol. 2011. 26:Suppl 1. 123–130.

2. Liu Y, Zhong Y, Zou Z, Xu Z, Li B, Ren X, et al. Features and clinical implications of hepatitis B virus genotypes and mutations in basal core promoter/precore region in 507 Chinese patients with acute and chronic hepatitis B. J Clin Virol. 2010. 47:243–247.

3. Kao JH, Chen PJ, Lai MY, Chen DS. Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology. 2003. 124:327–334.

4. Zheng JX, Zeng Z, Zheng YY, Yin SJ, Zhang DY, Yu YY, et al. Role of hepatitis B virus base core and precore/core promoter mutations on hepatocellular carcinoma in untreated older genotype C Chinese patients. J Viral Hepat. 2011. 18:e423–e431.

5. Carman WF, Zanetti AR, Karayiannis P, Water J, Manzillo G, Tonzi E, et al. Vaccine-induced escape mutant of hepatitis B virus. Lancet. 1990. 336:325–329.

6. Tabor E. Infections by hepatitis B surface antigen gene mutants in Europe and North America. J Med Virol. 2006. 78:Suppl 1. S43–S47.

7. Carman WF, Hadziyannis S, McGarvey MJ, Jacyna MR, Karayiannis P, Makris A, et al. Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet. 1989. 2:588–591.

8. Kim JK, Park YH, Chung WY, Kim CH. Mutations in Hepatitis B Virus precore and core promotor in children with chronic hepatitis B infection-comparison between vertical and non-vertical transmission. J Korean Pediatr Soc. 2000. 43:779–791.

9. Kang HS, Kang KS, Song BC. Precore and core promoter mutations of the hepatitis B virus gene in chronic genotype C-infected children. J Korean Med Sci. 2011. 26:546–550.

10. Yang HI, Yeh SH, Chen PJ, Iloeje UH, Jen CL, Su J, et al. Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma. J Natl Cancer Inst. 2008. 100:1134–1143.

11. Hsu HY, Chang MH, Ni YH, Chen HL. Survey of hepatitis B surface variant infection in children 15 years after a nationwide vaccination programme in Taiwan. Gut. 2004. 53:1499–1503.

12. Ni YH, Chen DS. Hepatitis B vaccination in children: the Taiwan experience. Pathol Biol. 2010. 58:296–300.

13. Zanetti AR, Tanzi E, Manzillo G, Maio G, Sbreglia C, Caporaso N, et al. Hepatitis B variant in Europe. Lancet. 1988. 2:1132–1133.

14. Hsu HY, Chang MH, Ni YH, Chen HL. Survey of hepatitis B surface variant infection in children 15 years after a nationwide vaccination programme in Taiwan. Gut. 2004. 53:1499–1503.

15. Song BC, Kim SH, Kim H, Ying YH, Kim HJ, Kim YJ, et al. Prevalence of naturally occurring surface antigen variants of hepatitis B virus in Korean patients infected chronically. J Med Virol. 2005. 76:194–202.