WILD-TYPE AND E-ANTIGEN-MINUS HEPATITIS-B VIRUSES AND COURSE OF CHRONIC HEPATITIS

被引:345
作者
BRUNETTO, MR
GIARIN, MM
OLIVERI, F
CHIABERGE, E
BALDI, M
ALFARANO, A
SERRA, A
SARACCO, G
VERME, G
WILL, H
BONINO, F
机构
[1] MOLINETTE MAURIZIANO HOSP,DIV GASTROENTEROL,CORSO BRAMANTE 88,I-10126 TURIN,ITALY
[2] UNIV TURIN,MED CLIN,I-10124 TURIN,ITALY
[3] MAX PLANCK INST BIOCHEM,W-8033 MARTINSRIED,GERMANY
关键词
HEPATITIS-B VIRUS DNA; HEPATITIS-B VIRUS VARIANT;
D O I
10.1073/pnas.88.10.4186
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Using an oligonucleotide hybridization assay, we studied the clinical implication of wild-type hepatitis B virus (HBV) and a HBV mutant that is unable to secrete hepatitis B e antigen (HBeAg) because of a translational defect due to a stop codon in the pre-C region in 106 hepatitis B surface antigen-positive patients with chronic hepatitis B. Wild-type HBV was detected in 31 of 42 (73.8%) HBeAg-positive patients, whereas a mixed viral population was present in 10 (23.8%). Significant differences in the severity and outcome of liver disease were not observed in the two groups of patients. However, the emergence of HBeAg-minus HBV in wild-type HBV carriers was associated with an exacerbation of liver disease and was followed by the presence of antibodies against HBeAg (anti-HBe) in serum in 50% of the cases. In 61 of 64 (95.3%) anti-HBe-positive patients, HBeAg-minus HBV was the predominant virus: HBeAg-minus HBV was detected in 42 patients (65.6%), whereas both wild-type and HBeAg-minus HBV were present in 19 (29.7%). HBeAg-minus HBV was associated with a course of hepatitis characterized by flare-ups of liver cell necrosis interspersed with periods of asymptomatic HBV carriage (P < 0.01). These data support the hypothesis that genetic heterogeneity of HBV significantly influences the course and outcome of chronic hepatitis B. Wild-type HBV secreting HBeAg induces immunologic tolerance and causes chronic infection. HBeAg-minus HBV might be unable to induce chronic infection without the helper function of wild-type HBV, but it appears to be more pathogenic. Once chronic infection is established, HBeAg-minus HBV variants may prevail and displace wild-type virus.
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页码:4186 / 4190
页数:5
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