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. 1988 Jan-Feb;61(1):61–83.

Liver lesions in hepatitis B viral infection.

V J Desmet 1
PMCID: PMC2590411  PMID: 2834884

Abstract

A review is made of the various histological lesions observed in hepatitis B virus-related liver diseases, including different forms of acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The elementary lesions discussed include acidophil necrosis (apoptosis), confluent lytic necrosis in its different patterns, piecemeal necrosis, focal necrosis, and dysplastic hepatocytes. Their pathogenesis is explained in the framework of recent developments in the immunopathology of hepatitis B viral infections.

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Selected References

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

  1. Anthony P. P., Vogel C. L., Barker L. F. Liver cell dysplasia: a premalignant condition. J Clin Pathol. 1973 Mar;26(3):217–223. [PMC free article] [PubMed] [Google Scholar]
  2. Baggenstoss A. H., Soloway R. D., Summerskill W. H., Elveback L. R., Schoenfield L. J. Chronic active liver disease. The range of histologic lesions, their response to treatment, and evolution. Hum Pathol. 1972 Jun;3(2):183–198. doi: 10.1016/s0046-8177(72)80072-8. [DOI] [PubMed] [Google Scholar]
  3. Bardadin K. A., Desmet V. J. Interdigitating and dendritic reticulum cells in chronic active hepatitis. Histopathology. 1984 Jul;8(4):657–667. doi: 10.1111/j.1365-2559.1984.tb02378.x. [DOI] [PubMed] [Google Scholar]
  4. Bardadin K. A., Desmet V. J. Ultrastructural observations on sinusoidal endothelial cells in chronic active hepatitis. Histopathology. 1985 Feb;9(2):171–181. doi: 10.1111/j.1365-2559.1985.tb02433.x. [DOI] [PubMed] [Google Scholar]
  5. Benacerraf B. Role of MHC gene products in immune regulation. Science. 1981 Jun 12;212(4500):1229–1238. doi: 10.1126/science.6165083. [DOI] [PubMed] [Google Scholar]
  6. Bianchi L., Gudat F. Immunopathology of hepatitis B. Prog Liver Dis. 1979;6:371–392. [PubMed] [Google Scholar]
  7. Bianchi L., Gudat F. Sanded nuclei in hepatitis B: eosinophilic inclusions in liver cell nuclei due to excess in hepatitis B core antigen formation. Lab Invest. 1976 Jul;35(1):1–5. [PubMed] [Google Scholar]
  8. Bianchi L. The immunopathology of acute type B hepatitis. Springer Semin Immunopathol. 1981 Apr;3(4):421–438. doi: 10.1007/BF01951491. [DOI] [PubMed] [Google Scholar]
  9. Boyer J. L. Chronic hepatitis--a perspective on classification and determinants of prognosis. Gastroenterology. 1976 Jun;70(6):1161–1171. [PubMed] [Google Scholar]
  10. Boyer J. L., Klatskin G. Pattern of necrosis in acute viral hepatitis. Prognostic value of bridging (subacute hepatic necrosis). N Engl J Med. 1970 Nov 12;283(20):1063–1071. doi: 10.1056/NEJM197011122832001. [DOI] [PubMed] [Google Scholar]
  11. Boyer J. L. The diagnosis and pathogenesis of clinical variants in viral hepatitis. Am J Clin Pathol. 1976 May;65(5 Suppl):898–908. [PubMed] [Google Scholar]
  12. Brattig N. W., Schrempf-Decker G. E., Bröckl C. W., Berg P. A. Immunosuppressive serum factors in viral hepatitis. II. Further characterization of serum inhibition factor as an albumin-associated molecule. Hepatology. 1983 Sep-Oct;3(5):647–655. doi: 10.1002/hep.1840030504. [DOI] [PubMed] [Google Scholar]
  13. Burrell C. J., Gowans E. J., Rowland R., Hall P., Jilbert A. R., Marmion B. P. Correlation between liver histology and markers of hepatitis B virus replication in infected patients: a study by in situ hybridization. Hepatology. 1984 Jan-Feb;4(1):20–24. doi: 10.1002/hep.1840040104. [DOI] [PubMed] [Google Scholar]
  14. Callea F., de Vos R., Togni R., Tardanico R., Vanstapel M. J., Desmet V. J. Fibrinogen inclusions in liver cells: a new type of ground-glass hepatocyte. Immune light and electron microscopic characterization. Histopathology. 1986 Jan;10(1):65–73. doi: 10.1111/j.1365-2559.1986.tb02461.x. [DOI] [PubMed] [Google Scholar]
  15. Chemello L., Mondelli M., Bortolotti F., Schiavon E., Pontisso P., Alberti A., Rondanelli E. G., Realdi G. Natural killer activity in patients with acute viral hepatitis. Clin Exp Immunol. 1986 Apr;64(1):59–64. [PMC free article] [PubMed] [Google Scholar]
  16. Chisari F. V., Nakamura M., Milich D. R., Han K., Molden D., Leroux-Roels G. G. Production of two distinct and independent hepatic immunoregulatory molecules by the perfused rat liver. Hepatology. 1985 Sep-Oct;5(5):735–743. doi: 10.1002/hep.1840050506. [DOI] [PubMed] [Google Scholar]
  17. Combes B. The initial morphologic lesion in chronic hepatitis, important or unimportant? Hepatology. 1986 May-Jun;6(3):518–522. doi: 10.1002/hep.1840060332. [DOI] [PubMed] [Google Scholar]
  18. Conn H. O. Chronic hepatitis: reducing an iatrogenic enigma to a workable puzzle. Gastroenterology. 1976 Jun;70(6):1182–1184. [PubMed] [Google Scholar]
  19. De Groote J., Desmet V. J., Gedigk P., Korb G., Popper H., Poulsen H., Scheuer P. J., Schmid M., Thaler H., Uehlinger E. A classification of chronic hepatitis. Lancet. 1968 Sep 14;2(7568):626–628. doi: 10.1016/s0140-6736(68)90710-1. [DOI] [PubMed] [Google Scholar]
  20. De Groote J., Fevery J., Lepoutre L. Long-term follow-up of chronic active hepatitis of moderate severity. Gut. 1978 Jun;19(6):510–513. doi: 10.1136/gut.19.6.510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. De Vos R., De Wolf-Peeters C., van den Oord J. J., Desmet V. Ultrastructural immunocytochemical demonstration of HLA class I antigens in human pathological liver tissue. Hepatology. 1985 Nov-Dec;5(6):1071–1075. doi: 10.1002/hep.1840050602. [DOI] [PubMed] [Google Scholar]
  22. Doherty P. C., Allan J. E. Role of the major histocompatibility complex in targeting effector T cells into a site of virus infection. Eur J Immunol. 1986 Oct;16(10):1237–1242. doi: 10.1002/eji.1830161009. [DOI] [PubMed] [Google Scholar]
  23. Dudley F. J., Fox R. A., Sherlock S. Cellular immunity and hepatitis-associated, Australia antigen liver disease. Lancet. 1972 Apr 1;1(7753):723–726. doi: 10.1016/s0140-6736(72)90234-6. [DOI] [PubMed] [Google Scholar]
  24. Eggink H. F., Houthoff H. J., Huitema S., Wolters G., Poppema S., Gips C. H. Cellular and humoral immune reactions in chronic active liver disease. II. Lymphocyte subsets and viral antigens in liver biopsies of patients with acute and chronic hepatitis B. Clin Exp Immunol. 1984 Apr;56(1):121–128. [PMC free article] [PubMed] [Google Scholar]
  25. Freemont A. J. A possible route for lymphocyte migration into diseased tissues. J Clin Pathol. 1983 Feb;36(2):161–166. doi: 10.1136/jcp.36.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Grol M., Schumacher K. Purification and biochemical characterization of human liver-derived inhibitory protein (LIP). J Immunol. 1983 Jan;130(1):323–326. [PubMed] [Google Scholar]
  27. Hadziyannis S., Gerber M. A., Vissoulis C., Popper H. Cytoplasmic hepatitis B antigen in "ground-glass" hepatocytes of carriers. Arch Pathol. 1973 Nov;96(5):327–330. [PubMed] [Google Scholar]
  28. Harrist T. J., Ruiter D. J., Mihm M. C., Jr, Bhan A. K. Distribution of major histocompatibility antigens in normal skin. Br J Dermatol. 1983 Dec;109(6):623–633. doi: 10.1111/j.1365-2133.1983.tb00540.x. [DOI] [PubMed] [Google Scholar]
  29. Hoofnagle J. H., Dusheiko G. M., Seeff L. B., Jones E. A., Waggoner J. G., Bales Z. B. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Ann Intern Med. 1981 Jun;94(6):744–748. doi: 10.7326/0003-4819-94-6-744. [DOI] [PubMed] [Google Scholar]
  30. Ikeda T., Pignatelli M., Lever A. M., Thomas H. C. Relationship of HLA protein display to activation of 2-5A synthetase in HBe antigen or anti-HBe positive chronic HBV infection. Gut. 1986 Dec;27(12):1498–1501. doi: 10.1136/gut.27.12.1498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. KLATSKIN G. Subacute hepatic necrosis and postnecrotic cirrhosis due to anicteric infections with the hepatitis virus. Am J Med. 1958 Sep;25(3):333–358. doi: 10.1016/0002-9343(58)90072-x. [DOI] [PubMed] [Google Scholar]
  32. Kerr J. F., Cooksley W. G., Searle J., Halliday J. W., Halliday W. J., Holder L., Roberts I., Burnett W., Powell L. W. The nature of piecemeal necrosis in chronic active hepatitis. Lancet. 1979 Oct 20;2(8147):827–828. doi: 10.1016/s0140-6736(79)92178-0. [DOI] [PubMed] [Google Scholar]
  33. Kojima T., Bloemen J., Desmet V. J. Immune electron microscopic demonstration of hepatitis B core antigen (HBcAg) in liver cell plasma membranes. Liver. 1987 Aug;7(4):191–200. doi: 10.1111/j.1600-0676.1987.tb00342.x. [DOI] [PubMed] [Google Scholar]
  34. Lampert I. A. Expression of HLA-DR (Ia like) antigen on epidermal keratinocytes in human dermatoses. Clin Exp Immunol. 1984 Jul;57(1):93–100. [PMC free article] [PubMed] [Google Scholar]
  35. Liaw Y. F., Chu C. M., Su I. J., Huang M. J., Lin D. Y., Chang-Chien C. S. Clinical and histological events preceding hepatitis B e antigen seroconversion in chronic type B hepatitis. Gastroenterology. 1983 Feb;84(2):216–219. [PubMed] [Google Scholar]
  36. Liaw Y. F., Yang S. S., Chen T. J., Chu C. M. Acute exacerbation in hepatitis B e antigen positive chronic type B hepatitis. A clinicopathological study. J Hepatol. 1985;1(3):227–233. doi: 10.1016/s0168-8278(85)80050-7. [DOI] [PubMed] [Google Scholar]
  37. MacSween R. N. Pathology of viral hepatitis and its sequelae. Clin Gastroenterol. 1980 Jan;9(1):23–45. [PubMed] [Google Scholar]
  38. Mizoguchi Y., Miyajima K., Sakagami Y., Yamamoto S., Morisawa S. Detection of the cholestatic factor in the liver tissue of patients with acute intrahepatic cholestasis. Ann Allergy. 1986 Apr;56(4):304–307. [PubMed] [Google Scholar]
  39. Mondelli M. U., Bortolotti F., Pontisso P., Rondanelli E. G., Williams R., Realdi G., Alberti A., Eddleston A. L. Definition of hepatitis B virus (HBV)-specific target antigens recognized by cytotoxic T cells in acute HBV infection. Clin Exp Immunol. 1987 May;68(2):242–250. [PMC free article] [PubMed] [Google Scholar]
  40. Mondelli M., Eddleston A. L. Mechanisms of liver cell injury in acute and chronic hepatitis B. Semin Liver Dis. 1984 Feb;4(1):47–58. doi: 10.1055/s-2008-1040645. [DOI] [PubMed] [Google Scholar]
  41. Montano L., Miescher G. C., Goodall A. H., Wiedmann K. H., Janossy G., Thomas H. C. Hepatitis B virus and HLA antigen display in the liver during chronic hepatitis B virus infection. Hepatology. 1982 Sep-Oct;2(5):557–561. doi: 10.1002/hep.1840020508. [DOI] [PubMed] [Google Scholar]
  42. Montaño L., Aranguibel F., Boffill M., Goodall A. H., Janossy G., Thomas H. C. An analysis of the composition of the inflammatory infiltrate in autoimmune and hepatitis B virus-induced chronic liver disease. Hepatology. 1983 May-Jun;3(3):292–296. doi: 10.1002/hep.1840030303. [DOI] [PubMed] [Google Scholar]
  43. Pignatelli M., Waters J., Lever A., Iwarson S., Gerety R., Thomas H. C. Cytotoxic T-cell responses to the nucleocapsid proteins of HBV in chronic hepatitis. Evidence that antibody modulation may cause protracted infection. J Hepatol. 1987 Feb;4(1):15–21. doi: 10.1016/s0168-8278(87)80004-1. [DOI] [PubMed] [Google Scholar]
  44. Popper H. Changing concepts of the evolution of chronic hepatitis and the role of piecemeal necrosis. Hepatology. 1983 Sep-Oct;3(5):758–762. doi: 10.1002/hep.1840030522. [DOI] [PubMed] [Google Scholar]
  45. Popper H., Schaffner F. The vocabulary of chronic hepatitis. N Engl J Med. 1971 May 20;284(20):1154–1156. doi: 10.1056/NEJM197105202842011. [DOI] [PubMed] [Google Scholar]
  46. Popper H. The relation between hepatitis B virus infection and hepatocellular carcinoma. Hepatogastroenterology. 1986 Feb;33(1):2–5. [PubMed] [Google Scholar]
  47. Rappaport A. M. The microcirculatory acinar concept of normal and pathological hepatic structure. Beitr Pathol. 1976 May;157(3):215–243. doi: 10.1016/s0005-8165(76)80083-2. [DOI] [PubMed] [Google Scholar]
  48. Scheuer P. J. Changing views on chronic hepatitis. Histopathology. 1986 Jan;10(1):1–4. doi: 10.1111/j.1365-2559.1986.tb02455.x. [DOI] [PubMed] [Google Scholar]
  49. Stacey N. H., Bishop C. J., Halliday J. W., Halliday W. J., Cooksley W. G., Powell L. W., Kerr J. F. Apoptosis as the mode of cell death in antibody-dependent lymphocytotoxicity. J Cell Sci. 1985 Mar;74:169–179. doi: 10.1242/jcs.74.1.169. [DOI] [PubMed] [Google Scholar]
  50. Thomas H. C., Pignatelli M., Scully L. J. Viruses and immune reactions in the liver. Scand J Gastroenterol Suppl. 1985;114:105–117. doi: 10.3109/00365528509093771. [DOI] [PubMed] [Google Scholar]
  51. Tranum-Jensen J., Bhakdi S. Freeze-fracture analysis of the membrane lesion of human complement. J Cell Biol. 1983 Sep;97(3):618–626. doi: 10.1083/jcb.97.3.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Unanue E. R., Beller D. I., Lu C. Y., Allen P. M. Antigen presentation: comments on its regulation and mechanism. J Immunol. 1984 Jan;132(1):1–5. [PubMed] [Google Scholar]
  53. Zinkernagel R. M., Doherty P. C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974 Apr 19;248(5450):701–702. doi: 10.1038/248701a0. [DOI] [PubMed] [Google Scholar]
  54. Zinkernagel R. M., Haenseler E., Leist T., Cerny A., Hengartner H., Althage A. T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay? J Exp Med. 1986 Oct 1;164(4):1075–1092. doi: 10.1084/jem.164.4.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. van den Oord J. J., Desmet V. J. Verteilungsmuster der Histokompatibilitäts-Hauptantigene im normalen und pathologischen Lebergewebe. Leber Magen Darm. 1984 Nov;14(6):244–254. [PubMed] [Google Scholar]
  56. van den Oord J. J., de Vos R., Desmet V. J. In situ distribution of major histocompatibility complex products and viral antigens in chronic hepatitis B virus infection: evidence that HBc-containing hepatocytes may express HLA-DR antigens. Hepatology. 1986 Sep-Oct;6(5):981–989. doi: 10.1002/hep.1840060529. [DOI] [PubMed] [Google Scholar]

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