Skip to main content
NCBI home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1994 Dec;47(12):1112–1115. doi: 10.1136/jcp.47.12.1112

Hepatic expression of tumour necrosis factor-alpha in chronic hepatitis B virus infection.

M J Hussain 1, J Y Lau 1, R Williams 1, D Vergani 1
PMCID: PMC502205  PMID: 7876386

Abstract

AIM--To determine the hepatic expression of tumour necrosis factor-alpha (TNF alpha) in patients with chronic hepatitis B virus (HBV) infection. METHODS--Frozen liver biopsy sections from 19 patients with chronic HBV infection were studied, 12 of whom were HBeAg positive and 10 serum HBV DNA positive. Hepatic expression of TNF alpha was determined using immunohistochemistry. RESULTS--Only infiltrating mononuclear cells showed immunoreactive staining for TNF alpha (median 2, range 0-3; n = 19) which appeared as diffuse positive staining material in the cytoplasm. Patients with active liver disease, assessed histologically and biochemically, had a higher level of expression, both in the number of TNF alpha positive cells and the proportion of TNF alpha positive infiltrating mononuclear cells. There was no correlation between the expression of TNF alpha and serological parameters of viral infection (HBeAg and HBV DNA status and HBV DNA concentrations). CONCLUSION--Hepatic expression of TNF alpha is increased in chronic HBV infection and is related to the activity of liver disease and not to the level of HBV replication.

Full text

PDF
1112

Images in this article

1113Image
on p.1113

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beutler B., Cerami A. The common mediator of shock, cachexia, and tumor necrosis. Adv Immunol. 1988;42:213–231. doi: 10.1016/s0065-2776(08)60846-9. [DOI] [PubMed] [Google Scholar]
  2. Chisari F. V., Ferrari C., Mondelli M. U. Hepatitis B virus structure and biology. Microb Pathog. 1989 May;6(5):311–325. doi: 10.1016/0882-4010(89)90073-9. [DOI] [PubMed] [Google Scholar]
  3. Daniels H. M., Meager A., Eddleston A. L., Alexander G. J., Williams R. Spontaneous production of tumour necrosis factor alpha and interleukin-1 beta during interferon-alpha treatment of chronic HBV infection. Lancet. 1990 Apr 14;335(8694):875–877. doi: 10.1016/0140-6736(90)90475-k. [DOI] [PubMed] [Google Scholar]
  4. Fagan E. A., Guarner P., Perera S. D., Trowbridge R., Rolando N., Davison F., Williams R. Quantitation of hepatitis B virus DNA (HBV DNA) in serum using the spot hybridization technique and scintillation counting. J Virol Methods. 1985 Dec;12(3-4):251–262. doi: 10.1016/0166-0934(85)90136-3. [DOI] [PubMed] [Google Scholar]
  5. Folks T. M., Clouse K. A., Justement J., Rabson A., Duh E., Kehrl J. H., Fauci A. S. Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2365–2368. doi: 10.1073/pnas.86.7.2365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gerber M. A., Thung S. N. Molecular and cellular pathology of hepatitis B. Lab Invest. 1985 Jun;52(6):572–590. [PubMed] [Google Scholar]
  7. Gilles P. N., Guerrette D. L., Ulevitch R. J., Schreiber R. D., Chisari F. V. HBsAg retention sensitizes the hepatocyte to injury by physiological concentrations of interferon-gamma. Hepatology. 1992 Sep;16(3):655–663. doi: 10.1002/hep.1840160308. [DOI] [PubMed] [Google Scholar]
  8. Ikeda T., Lever A. M., Thomas H. C. Evidence for a deficiency of interferon production in patients with chronic hepatitis B virus infection acquired in adult life. Hepatology. 1986 Sep-Oct;6(5):962–965. doi: 10.1002/hep.1840060525. [DOI] [PubMed] [Google Scholar]
  9. Lau J. Y., Bird G. L., Naoumov N. V., Williams R. Hepatic HLA antigen display in chronic hepatitis B virus infection. Relation to hepatic expression of HBV genome/gene products and liver histology. Dig Dis Sci. 1993 May;38(5):888–895. doi: 10.1007/BF01295916. [DOI] [PubMed] [Google Scholar]
  10. Lau J. Y., Sheron N., Nouri-Aria K. T., Alexander G. J., Williams R. Increased tumor necrosis factor-alpha receptor number in chronic hepatitis B virus infection. Hepatology. 1991 Jul;14(1):44–50. doi: 10.1002/hep.1840140108. [DOI] [PubMed] [Google Scholar]
  11. Mestan J., Digel W., Mittnacht S., Hillen H., Blohm D., Möller A., Jacobsen H., Kirchner H. Antiviral effects of recombinant tumour necrosis factor in vitro. 1986 Oct 30-Nov 5Nature. 323(6091):816–819. doi: 10.1038/323816a0. [DOI] [PubMed] [Google Scholar]
  12. Mieli-Vergani G., Vergani D., Portmann B., White Y., Murray-Lyon I., Marigold J. H., Woolf I., Eddleston A. L., Williams R. Lymphocyte cytotoxicity to autologous hepatocytes in HBsAg positive chronic liver disease. Gut. 1982 Dec;23(12):1029–1036. doi: 10.1136/gut.23.12.1029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Missale G., Brems J. J., Takiff H., Pockros P. J., Chisari F. V. Human leukocyte antigen class I-independent pathways may contribute to hepatitis B virus-induced liver disease after liver transplantation. Hepatology. 1993 Sep;18(3):491–496. [PubMed] [Google Scholar]
  14. Mondelli M., Vergani G. M., Alberti A., Vergani D., Portmann B., Eddleston A. L., Williams R. Specificity of T lymphocyte cytotoxicity to autologous hepatocytes in chronic hepatitis B virus infection: evidence that T cells are directed against HBV core antigen expressed on hepatocytes. J Immunol. 1982 Dec;129(6):2773–2778. [PubMed] [Google Scholar]
  15. Nouri-Aria K. T., Magrin S., Alexander G. J., Anderson M. G., Williams R., Eddleston A. L. Abnormal T-cell activation in chronic hepatitis B viral infection: a consequence of monocyte dysfunction? Immunology. 1988 Aug;64(4):733–738. [PMC free article] [PubMed] [Google Scholar]
  16. Onji M., Lever A. M., Saito I., Thomas H. C. Defective response to interferons in cells transfected with the hepatitis B virus genome. Hepatology. 1989 Jan;9(1):92–96. doi: 10.1002/hep.1840090115. [DOI] [PubMed] [Google Scholar]
  17. Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sheron N., Lau J. Y., Daniels H. M., Webster J., Eddleston A. L., Alexander G. J., Williams R. Tumour necrosis factor to treat chronic hepatitis B virus infection. Lancet. 1990 Aug 4;336(8710):321–322. doi: 10.1016/0140-6736(90)91866-9. [DOI] [PubMed] [Google Scholar]
  19. Sheron N., Lau J., Daniels H., Goka J., Eddleston A., Alexander G. J., Williams R. Increased production of tumour necrosis factor alpha in chronic hepatitis B virus infection. J Hepatol. 1991 Mar;12(2):241–245. doi: 10.1016/0168-8278(91)90945-8. [DOI] [PubMed] [Google Scholar]
  20. Tracey K. J., Vlassara H., Cerami A. Cachectin/tumour necrosis factor. Lancet. 1989 May 20;1(8647):1122–1126. doi: 10.1016/s0140-6736(89)92394-5. [DOI] [PubMed] [Google Scholar]
  21. Volpes R., van den Oord J. J., De Vos R., Desmet V. J. Hepatic expression of type A and type B receptors for tumor necrosis factor. J Hepatol. 1992 Mar;14(2-3):361–369. doi: 10.1016/0168-8278(92)90184-q. [DOI] [PubMed] [Google Scholar]
  22. Wong G. H., Goeddel D. V. Tumour necrosis factors alpha and beta inhibit virus replication and synergize with interferons. 1986 Oct 30-Nov 5Nature. 323(6091):819–822. doi: 10.1038/323819a0. [DOI] [PubMed] [Google Scholar]
  23. Yoshioka K., Kakumu S., Arao M., Tsutsumi Y., Inoue M., Wakita T., Ishikawa T., Mizokami M. Immunohistochemical studies of intrahepatic tumour necrosis factor alpha in chronic liver disease. J Clin Pathol. 1990 Apr;43(4):298–302. doi: 10.1136/jcp.43.4.298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zachoval R., Abb J., Zachoval V., Eisenburg J., Pape G. R., Paumgartner G., Deinhardt F. Interferon alpha in hepatitis type B and non-A, non-B. Defective production by peripheral blood mononuclear cells in chronic infection and development of serum interferon in acute disease. J Hepatol. 1988 Jun;6(3):364–368. doi: 10.1016/s0168-8278(88)80055-2. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES