1887

Abstract

In the Mediterranean region almost all patients with hepatitis B virus (HBV)-related cirrhosis are anti-HBV e antigen (anti-HBeAg)-positive and carriers of HBeAg-negative virus mutants. The six members of a family who acquired HBV infection were recently studied: two siblings developed cirrhosis with persistence of HBeAg positivity, whereas their parents and two more siblings cleared the virus. The two cirrhotic patients showed homozygosity for HLA class I by phenotype, which is a rare occurrence in the general population, while the other family members were heterozygous for HLA class I. The sequencing analyses of the entire viral DNAs isolated from both cirrhotic patients showed that the two viral genomes were almost identical and no mutation preventing HBeAg synthesis or viral gene expression was present. These findings might suggest that homozygosity for HLA class I molecules might be responsible for an insufficient response to the virus, favouring chronic outcome of the infection and the long-lasting persistence of HBV populations that produce HBeAg.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-77-8-1833
1996-08-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/77/8/JV0770081833.html?itemId=/content/journal/jgv/10.1099/0022-1317-77-8-1833&mimeType=html&fmt=ahah

References

  1. Bertoletti A., Sette A., Chisari F. V., Penna A., Levrero M., De Carli M., Fiaccadori F., Ferrari C. 1994a; Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells. Nature 369:407–410
    [Google Scholar]
  2. Bertoletti A., Costanzo A., Chisari F. V., Levrero M., Artini M., Sette A., Penna A., Giuberti T., Fiaccadori F., Ferrari C. 1994b; Cytotoxic T lymphocyte response to a wild type hepatitis B virus epitope in patients chronically infected by variant viruses carrying substitutions within the epitope. Journal of Experimental Medicine 180:933–943
    [Google Scholar]
  3. Bonino F., Rosina F., Rizzetto M., Rizzi R., Chiaberge E., Tardanico R., Callea F., Verme G. 1986; Chronic hepatitis in HBsAg carriers with serum HBV-DNA and anti-HBe. Gastroenterology 90:1268–1273
    [Google Scholar]
  4. Brunetto M. R., Giarin E., Oliveri F., Chiaberge E., Baldi M., Alfarano A., Serra A., Saraocco G., Verme G., Will H., Bonino F. 1991; Wild type and e antigen-deficient hepatitis B viruses and course of chronic hepatitis. Proceedings of the National Academy of Sciences, USA 88:4186–4190
    [Google Scholar]
  5. Brunetto M. R., Stemler M., Schodell F., Will H., Ottobrelli A., Rizzetto M., Verme G., Bonino F. 1989; Identification of HBV variants which cannot produce precore derived HBeAg and may be responsible for severe hepatitis. Italian Journal of Gastroenterology 21:151–154
    [Google Scholar]
  6. Carman W. F., Jacyna M. R., Hadziyannis S., Karayiannis P., McGarbey M. J., Makris A., Thomas H. C. 1989; Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet ii:588–591
    [Google Scholar]
  7. Chisari F. V., Ferrari C. 1995; Hepatitis B immunopathogenesis. Annual Review of Immunology 13:29–60
    [Google Scholar]
  8. Galibert F., MANDART E., Fitoussi F., Tiollais P., Charney P. 1979; Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in £. coli . Nature 281:646–650
    [Google Scholar]
  9. Gregorio G. V., Mieli-Vergani G., Mowat A. P. 1993; Neonatal and pediatric infection. In Viral hepatitis, scientific bases and clinical management pp 541–563 Edited by Zuckerman A. J., Thomas H. C. London: Churchill Livingstone;
    [Google Scholar]
  10. Hamasaki K., Nakata K., Nagayama Y., Ohtsuru A., Daikoku M., Taniguchi K., Tzutzumi T., Sato Y., Kato Y., Nagataki S. 1994; Changes in the prevalence of HBeAg-negative mutant hepatitis B virus during the course of chronic hepatitis B. Hepatology 20:8–14
    [Google Scholar]
  11. Hoofnagle J., Dusheiko G., Seef L., Jones E., Waggoner J., Bales Z. B. 1981; Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Annals of Internal Medicine 94:744–748
    [Google Scholar]
  12. Lieberman H. M., Labrecque D. R., Kew M. C., Hadzyiannis S. J., Shafritz D. A. 1983; Detection of hepatitis B virus directly in human serum by a simplified molecular hybridization test. Comparison to HBeAg/anti-HBe status in HBsAg carriers. Hepatology 3:285–291
    [Google Scholar]
  13. Lok A. S. F., Akarca U., Greene S. 1994; Mutations in the precore region of hepatitis B virus serve to enhance the stability of the secondary structure of the pregenome encapsidation signal. Proceedings of the National Academy of Sciences, USA 91:4077–4081
    [Google Scholar]
  14. Okamoto H., Yotsumoto S., Akahane Y., Yamanaka T., Miyazaki Y., Sugai Y., Tzuda F., Tanaka T., Miyakawa Y., Mayumi M. 1990; Hepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen. Virology 64:1298–1303
    [Google Scholar]
  15. Pollicino T., Campo S., Raimondo G. 1995; Pre-S and core gene heterogeneity in hepatitis B virus (HBV) genomes isolated from patients with long-lasting HBV chronic infection. Virology 208:672–677
    [Google Scholar]
  16. Raimondo G., Schneider R., Stemler M., Smedile V., Rodin G., Will H. 1990a; A new hepatitis B virus variant in a chronic carrier with multiple episodes of viral reactivation and acute hepatitis. Virology 179:64–68
    [Google Scholar]
  17. Raimondo G., Stemler M., Schneider R., Wildner G., Squadrito G., Will H. 1990b; Latency and reactivation of a precore mutant hepatitis B virus in a chronically infected patients. Journal of Hepatology 11:374–380
    [Google Scholar]
  18. Realdi G., Alberti A., Rugge M., Bortolotti F., Rigoli A. M., Tremolada F., Ruol A. 1980; Seroconversion from hepatitis B e antigen to anti-HBe in chronic hepatitis virus infection. Gastroenterology 79:195–199
    [Google Scholar]
  19. Takayanagi M., Kakumu S., Ishikawa T., Yasuyuki H., Yoshioka K., Wakita T. 1993; Comparison of envelop and precore/core variants of hepatitis B virus (HBV) during chronic HBV infection. Virology 196:138–145
    [Google Scholar]
  20. Thursz M. R., Kwiatkowski D., Allscop C. E. M., Greenwood B. M., Thomas H. C., Hill A. V. S. 1995; Association between an MHC class II allele and clearance of hepatitis B virus in the Gambia. New England Journal of Medicine 332:1065–1069
    [Google Scholar]
  21. Tur-Kaspa R., Keshet E., Eliakim M., Shouval D. 1984; Detection and characterization of hepatitis B virus DNA in serum of HBeAg-negative HBsAg carriers. Journal of Medical Virology 14:17–26
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-77-8-1833
Loading
/content/journal/jgv/10.1099/0022-1317-77-8-1833
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error