Mutations of T-Cell Epitopes in the Hepatitis B Virus Surface Gene in Children With Chronic Infectio

[Guest guest]

The American Journal of Gastroenterology (OnlineEarly Articles).

doi:10.1111/j.1572-0241.2007.01727.x

Abstract

Mutations of T-Cell Epitopes in the Hepatitis B Virus Surface Gene in Children

With Chronic Infection and Hepatocellular Carcinoma

Yen-Hsuan Ni, M.D., Ph.D.11Pediatrics, Mei-Hwei Chang, M.D.11Pediatrics,

Hong-Yuan Hsu, M.D., Ph.D.11Pediatrics, Yi-Ching Tung, M.D.11Pediatrics,

Huey-Ling Chen, M.D., Ph.D.11Pediatrics, Kuan-Jan Wang, M.S.11Pediatrics,

Daw-Jen Tsuei, Ph.D.11Pediatrics, and Ni-Chi Young, M.S.22Clinical Pathology,

National Taiwan University Hospital and National Taiwan University College of

Medicine, Taipei, TaiwanDepartments of 1Pediatrics and 2Clinical Pathology,

National Taiwan University Hospital and National Taiwan University College of

Medicine, Taipei, Taiwan

Reprint requests and correspondence: Mei-Hwei Chang, M.D., Department of

Pediatrics, College of Medicine and Hospital, National Taiwan University,

Taipei, Taiwan.

(Am J Gastroenterol 2007;102:1-6)

Abstract

BACKGROUND AND OBJECTIVES: Hepatitis B virus (HBV) infection induces an

interaction of host immune responses against virus antigen-presenting

hepatocytes. The emergence of mutants is a strategy through which the virus can

escape host attacks and produce chronic infection. In this study, we aimed to

investigate mutations of the human leukocyte antigen-A2-restricted T-cell

epitope (TCE) in chronic HBV-infected children.

METHODS: In total, 441 chronic HBV-infected children were longitudinally

followed-up every 6 months. They were divided into hepatitis B e antigen (HBeAg)

(−) (N = 60) and HBeAg (+) (N = 381) groups according to this seromarker at

their enrollment. The HBeAg (+) group was further divided into HBeAg (+/−) (N

= 229) and HBeAg (+/+) (N = 152) groups, depending on the occurrence of

spontaneous HBeAg seroconversion. Twenty-five children with HBV-related

hepatocellular carcinoma (HCC) were also recruited. TCE mutations were examined

using the latest serum samples, and serum samples at enrollment were used if TCE

mutations were present in the latest serum samples in the seroconverters. HBV

genotypes and liver enzymes were also analyzed.

RESULTS: The HBeAg (+/+) group had a lower TCE mutation rate (7.9%) than that

of the HBeAg (+/−) (29.2%), HBeAg (−) (26.7%), and HCC (28.0%) groups. In

the HBeAg (+/−) group, TCE mutations were present before HBeAg seroconversion

in 11.9% of the subjects. Those with TCE mutations showed HBeAg seroconversion

at an older age (16.1 ± 5.3 yr vs 12.7 ± 5.7 yr, P < 0.001) and with higher

peak alanine aminotransferase (ALT) levels (median 175 U/L vs 119 U/L, P = 0.03)

than those without TCE mutations.

CONCLUSIONS: TCE mutations tended to be positively associated with HBeAg

seroconversion and higher ALT levels in chronic HBV-infected children.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1572-0241.2007.01727.x

_________________________________________________________________

Get the power of Windows + Web with the new Windows Live.

http://www.windowslive.com?ocid=TXT_TAGHM_Wave2_powerofwindows_012008