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Hepatitis non-A, non-B (HNANB): Epidemiologische, klinische, serologische und morphologische Aspekte

Hepatitis non-A, non-B (HNANB): Epidemiological features, clinical presentation, serologic tests and morphology

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Summary

Hepatitis non-A, non-B (HNANB) is due to one or more transmissible agents, probably viruses. Epidemiologically, HNANB is transmitted predominantly by transfusion of blood or plasma derivatives, and percutaneous inoculation, but a non-percutaneous transmission by the fecal-oral route is also established. However, despite 10 years of intense world-wide research, the transmissible agent, or agents, have not been identified and there are no serological assays for either an antigen or an antibody that can be used to detect this infection. The clinical diagnosis of HNANB remains, therefore, a diagnosis of exclusion mainly of hepatitis A and B, Epstein-Barr virus, cytomegalovirus and drug-induced liver disease.

In contrast to hepatitis A and B, the clinical and biochemical course of HNANB tends to be less severe and the proportion of asymptomatic and anicteric cases is higher, but fulminant hepatitis and fatalities also occur. Typically, there is a fluctuating waxing and waning pattern of the serum aminotransferase activities in HNANB.

HNANB has a relative high tendency to progress to a chronic stage. The exact frequency of HNANB-induced liver cirrhosis and convincing evidence for an association with hepatocellular carcinoma cannot be assessed, although the persistence of the infectious agent in chronic HNANB and the existence of a chronic asymptomatic carrier state have been proved.

By light microscopy there is a broad morphologic spectrum of acute and chronic viral hepatitis, but no single pathognomonic lesion exists that allows a reliable distinction to be made of HNANB from hepatitis A and B.

Electron microscopy of liver biopsy specimens of chimpanzees, experimentally infected with HNANB agents, permits the visualisation of cytoplasmic changes, which appear to be specific for infection with HNANB viruses.

In human liver biopsy specimens from patients with HNANB, identical ultrastructural cytoplasmic changes could not consistently be demonstrated. In contrast, intranuclear aggregates of spherical and tubular particles measuring 20–29 nm, first described in experimental HNANB in chimpanzees, have been repeatedly demonstrated in acute and chronic HNANB in man. These nuclear particles have been considered as compelling evidence of human HNANB infection. The specificity has been challenged, however, by the demonstration of identical particles in other viral and non-viral hepatopathies and in liver biopsies of healthy volunteers. By immune electron microscopy, a multiplicity of virus-like particles are described in association with HNANB. The particles have been identified in sera of patients with HNANB, in sera of experimentally infected chimpanzees, and in infectious factor VIII and fibrinogen preparations. The great variability in morphology and size of the observed particles suggests the possibility that most of these particles are not specific for HNANB.

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Abbreviations

HNANB:

Hepatitis non-A, non-B

Literatur

  1. Aach RD, Lander JJ, Sherman LA, Miller WV, Kahn RA, Gitnick GL, Hollinger FB, Werch J, Szmuness W, Stevens CE, Kellner A, Weiner JM, Mosley JW (1978) Transfusions-transmitted viruses: interim analysis of hepatitis among transfused and nontransfused patients. In: Vyas GN, Cohen SN, Schmid R (eds) Viral hepatitis: etiology, epidemiology, pathogenesis and prevention. Franklin Institute Press, Philadelphia, pp 383–396

    Google Scholar 

  2. Aach RD, Szmuness W, Mosley JW, Holliger FB, Kahn RA, Stevens CE, Edwards VM, Werch J (1981) Serum alanine amino-transferase of donors in relation to the risk of non-A, non-B hepatitis in recipients: the transfusion-transmitted viruses study. New Engl J Med 304:989–994

    Google Scholar 

  3. Alberti A, Realdi G, Bortolotti F, Cadrobbi P, Barbiere R, Tremolada F, Ongaro G (1981) Detection by immunofluorescence of an antigen-antibody system in patients with acute and chronic non-A, non-B hepatitis. Liver 1:183–190

    Google Scholar 

  4. Alter HJ (1984) Resolved and unresolved issues in non-A, non-B hepatitis. In: Williams R, Maddrey WC (eds) Butterworths International Medical Reviews, Gastroenterology 4: Liver, Butterworths, London, pp 165–190

    Google Scholar 

  5. Alter HJ, Holland PV, Morrow AG, Purcell RH, Feinstone SM, Moritsugu Y (1975) Clinical and serological analysis of transfusion-associated hepatitis. Lancet II:838–841

    Google Scholar 

  6. Alter HJ, Purcell RH, Feinstone SM, Holland PV, Morrow AG (1978) Non-A, non-B hepatitis: a review and interim report of an ongoing prospective study. In: Vyas GN, Cohen SN, Schmid R (eds) Viral hepatitis: etiology, epidemiology, pathogenesis and prevention. Franklin Institute Press, Philadelphia, pp 359–369

    Google Scholar 

  7. Alter HJ, Purcell RH, Holland PV, Popper H (1978) Transmissible agent in non-A, non-B hepatitis. Lancet I:459–462

    Google Scholar 

  8. Alter HJ, Purcell RH, Feinstone SM, Tegtmeier GE (1982) Non-A, non-B hepatitis: its relationship to cytomegalovirus, to chronic hepatitis, and to direct and indirect test methods. In: Szmuness W, Alter HJ, Maynard JE (eds) Viral hepatitis: 1981 International Symposium. Franklin Institute Press, Philadelphia, pp 279–294

    Google Scholar 

  9. Alter MJ, Gerety RJ, Sampliner RE, Maddrey WC, Smallwood L, Tabor E, Matanoski GM, Nathanson N (1980) Acute non-A, non-B hepatitis in an urban population. Gastroenterology 79: 1000

    Google Scholar 

  10. Alter MJ, Gerety RJ, Smallwood LA, Sampliner RE, Tabor E, Deinhardt F, Frösner G, Matanoski GM (1982) Sporadic non-A, non-B hepatitis: frequency and epidemiology in an urban U.S. population. J infect Dis 145:886–893

    Google Scholar 

  11. Altorfer J, Roten A, Pirovino M, Bühler H, Frösner G, Schmid M (1981) Non-A-non-B-Virushepatitis: Häufigkeit, Epidemiologie und Prognose. Schweiz med Wochenschr 111:799–800

    Google Scholar 

  12. Altorfer J, Pirovino M, Bänninger P, Heer M, Grob PJ, Gudat F, Bianchi L, Schmid M (1983) Langzeitverlauf der sporadischen Non-A-non-B-Hepatitis: eine biochemische, immunologische und histologische Verlaufsstudie. Schweiz med Wochenschr 113:485–487.

    Google Scholar 

  13. Arnold W (1983) Serologische und morphologische Befunde bei Hepatitis non-A, non-B. Dtsch med Wochenschr 108:1925–1927

    Google Scholar 

  14. Arnold W, Reiter HJ, Martini GA, Meyer zum Büschenfelde KH (1980) Solide phase radioimmunoassay for the determination of non-A, non-B antigen and antibody. Gastroenterology 79:1098

    Google Scholar 

  15. Ayoola EA, Atoba MA (1982) Circulating immune complexes and serum complement in acute non-A, non-B hepatitis (NANBH). Hepatology 2:154

    Google Scholar 

  16. Ayoola EA, Odelola HA, Johnson AOK (1982) Primary liver cancer (PLC) after non-A, non-B hepatitis (NANBH). Hepatology 2:154

    Google Scholar 

  17. Balayan MS, Andjaparidze AG, Savinskaya SS, Ketiladze ES, Braginsky DM, Savinov AP, Poleschuk VF (1983) Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology 20:23–31

    Google Scholar 

  18. Bamber M, Murray A, Arborgh BAM, Scheuer PJ, Kernoff PBA, Thomas HC, Sherlock S (1981) Short incubation non-A, non-B hepatitis transmitted by factor VIII concentrates in patients with congenital coagulation disorders. Gut 22:854–859

    Google Scholar 

  19. Bamber M, Murray A, Lewin J, Thomas HC, Sherlock S (1981) Ultrastructural features in chronic non-A, non-B (NANB) hepatitis: a controlled blind study. J Med Virol 8:267–275

    Google Scholar 

  20. Bamber M, Murray A, Kernoff PB, Thomas HC (1981) Short incubation non-A, non-B heaptitis transmitted by factor VIII concentrates in patients with congenital coagulation disorders: a preliminary report of an antigen/antibody system. Med Lab Sci 38:373–378

    Google Scholar 

  21. Bamber M, Murray AK, Weller IVD, Morelli A, Scheuer PJ, Thomas HC, Sherlock S (1981) Clinical and histological features of a group of patients with sporadic non-A, non-B hepatitis. J Clin Path 34:1175–1180

    Google Scholar 

  22. Baptista A, Bianchi L, De Groote J, Desmet VJ, Gedigk P, Ishak KG, Korb G, Mac Sween RNM, Popper H, Poulsen H, Scheuer PJ, Schmid M, Thaler H, Wepler W (1983) Histopathology of the intrahepatic biliary tree. Liver 3:161–176

    Google Scholar 

  23. Berg PA, Stromp R, Ewers C, Schmeisser W, Dölle W, Flehmig B (1980) Epidemiologie und Klinik der Non-A-Non-B-Hepatitis. Dtsch Med Wochenschr 105:751–755

    Google Scholar 

  24. Berman M, Alter HJ, Ishak KG, Purcell RH, Jones EA (1979) The chronic sequelae of non-A, non-B hepatitis. Ann Int Med 91:1–6

    Google Scholar 

  25. Bianchi L (1981) Virus und Leber — Nicht-A/Nicht-B-Hepatitis: Stand Mai 1981. Verh Dtsch Ges Path 65:71–75

    Google Scholar 

  26. Bianchi L, Gudat F (1983) Histo- and immunpathology of viral heatitis. In: Deinhardt F, Deinhardt J (eds) Viral heatitis, laboratory and clinical science. Marcel Dekker, New York, pp 335–382

    Google Scholar 

  27. Bianchi L, Spichtin HP, Gudat F (1983) Die non-A-non-B-Hepatitis. Ein Fortschrittsbericht. Schweiz Med Wochenschr 113:478–484

    Google Scholar 

  28. Bradley DW, Maynard JE (1983) Non-A, non-B hepatitis: research progress and current perspectives. In: Second WHO/IABS symposium on viral hepatitis: standardization in immunoprophylaxis of infections by hepatitis viruses, Athens, Greece, 1982. Develop biol Standard 54:463–473

    Google Scholar 

  29. Bradley DW, Cook EH, Maynard JE, McCaustland KA, Ebert JW, Dolana GH, Petzel RA, Kantor RJ, Heibrunn A, Fields HA, Murphy BL (1979) Experimental infection of chimpanzees with antihemophilic (factor VIII) materials: recovery of virus-like particles associated with non-A, non-B hepatitis. J Med Virol 3:253–269

    Google Scholar 

  30. Bradley DW, Maynard JE, Cook EH, Ebert JW, Gravelle CR, Tsiquaye KN, Kessler H, Zuckerman AJ, Miller MF, Ling C, Overby LR (1980) Non-A/non-B hepatitis in experimentally infected chimpanzees: cross-challenge and electron microscopic studies: J Med Virol 6:185–201

    Google Scholar 

  31. Bradley DW, Maynard JE, Popper H, Ebert JW, Cook EH, Fields HA, Kemler BJ (1981) Persistent non-A, non-B hepatitis in experimentally infected chimpanzees. J Infect Dis 143:210–218

    Google Scholar 

  32. Bradley DW, Maynard JE, Krawczynski KZ, Popper H, Cook EH, Gravelle CR, Ebert JW (1982) Non-A/non-B hepatitis in chimpanzees infected with a factor VIII agent: evidence of persistent hepatic disease. In: Szmuness W, Alter HJ, Maynard JE (eds) Viral hepatitis: 1981 International Symposium. Franklin Institute Press, Philadelphia, pp 319–329

    Google Scholar 

  33. Bradley DW, Maynard JE, McCaustland KA, Murphy BL, Cook EH, Ebert JW (1983) Non-A, non-B hepatitis in chimpanzees: interference with acute hepatitis A virus and chronic hepatitis B virus infections. J Med Virol 11:207–213

    Google Scholar 

  34. Brotman B, Prince AM, Huima T, Richardson L, van den Ende MC, Pfeifer U (1983) Interference between non-A, non-B and hepatitis B virus infection in chimpanzees. J Med Virol 11:191–205

    Google Scholar 

  35. Burk KH, Cabral GA, Dreesman GR, Peters RL, Alter HJ (1981) Ultrastructural changes and virus-like particles localized in liver hepatocytes of chimpanzees infected with non-A, non-B hepatitis. J Med Virol 7:1–19

    Google Scholar 

  36. Busachi CA, Realdi G, Badiali-de Giorgi L, Alberti A (1980) Hepatocellular ultrastructural changes in patients with acute and chronic non-A, non-B hepatitis. J Submicr Cytol 12:681–686

    Google Scholar 

  37. Busachi CA, Realdi G, Alberti A, Badiali-de Giorgi L, Tremolada F (1981) Ultrastructural changes in the liver of patients with chronic non-A, non-B hepatitis. J Med Virol 7:205–212

    Google Scholar 

  38. Cabral GA, Marciano-Cabral F, Patterson M, Galen EA, Carithers RL (1981) Nuclear changes in hepatocytes of patients with non-A, non-B hepatitis. Gastroenterology 81:120–125

    Google Scholar 

  39. Caredda F, D'Arminio Monforte A, Lopez S, Culrado D, Moroni M (1979) Epidemiology of non-A, non-B hepatitis. Lancet II:1380

    Google Scholar 

  40. Chircu LV, Pezzella M, Lacava V, Ricci G (1980) Post-transfusion hepatitis: antigen/antibody systems correlated with non-A, non-B hepatitis. J Med Virol 6:147–151

    Google Scholar 

  41. Cossart YE, Field AM, Cant B, Widdows D (1975) Parvoviruslike particles in human sera. Lancet I:72–73

    Google Scholar 

  42. Cossart YE, Kirsch S, Ismay SL (1982) Post-transfusion hepatitis in Australia. Lancet I:208–213

    Google Scholar 

  43. Coursaget P, Maupas Ph, Dubois F, Drucker J, Goudeau A (1978) Hépatites non-A, non-B chez six malades hémodialysés. Nouv Presse méd 7:3515–3519

    Google Scholar 

  44. Coursaget P, Maupas Ph, Levin P, Barin F (1979) Virus-like particles associated with non-A, non-B hepatitis. Lancet II:92

    Google Scholar 

  45. De Vos R, De Wolf-Peeters C, Vanstapel MJ, Callea F, De Groote G, Desmyter J, Mortelmans J, Fevery J, De Groote J, Desmet VJ (1982) New ultrastructural marker in hepatocytes in non-A, non-B viral hepatitis. Liver 2:35–44

    Google Scholar 

  46. De Vos R, Vanstapel MJ, Desmyter J, De Wolf-Peeters C, De Groote G, Colaert J, Mortelmans J, De Groote J, Fevery J, Desmet V (1983) Are nuclear particles specific for non-A, non-B hepatitis? Hepatology 3:532–544

    Google Scholar 

  47. De Wolf-Peeters C, de Vos R, Desmet VJ, Fevery J (1981) A light microscopic marker of non-A, non-B viral hepatitis. J Clin Path 34:814

    Google Scholar 

  48. De Wolf-Peeters C, De Vos R, Desmet V, Ray MB, Desmyter J, De Groote G, Fevery J, Broeckaert L, De Groote J (1981) Human non-A, non-B hepatitis: Ultrastructural alterations in hepatocytes. Liver 1:50–55

    Google Scholar 

  49. Dienes HP, Popper H, Purcell RH, Bonino F, Ponzetto A (1981) Histopathologischer Ablauf von Virus B und non-A, non-B Hepatitis bei gleichzeitiger Inokulation der Erreger auf einen Schimpansen. Verh Dtsch Ges Path 65:91–95

    Google Scholar 

  50. Dienes HP, Popper H, Arnold W, Lobeck H (1982) Histologic observations in human hepatitis non-A, non-B. Hepatology 2:562–571

    Google Scholar 

  51. Dienstag JL (1983) Non-A, non-B hepatitis. I. Recognition, epidemiology, and clinical features. Gastroenterology 85:439–462

    Google Scholar 

  52. Dienstag JL (1983) Non-A, non-B hepatitis. II. Experimental transmission, putative virus agents and markers, and prevention. Gastroenterology 85:743–768

    Google Scholar 

  53. Dienstag JL, Alaama A, Mosley JW, Redeker AG, Purcell RH (1977) Etiology of sporadic hepatitis B surface antigen-negative hepatitis. Ann Int Med 87:1–6

    Google Scholar 

  54. Dienstag JL, Bhan AK, Alter HJ, Feinstone SM, Purcell RH (1979) Circulating immune complexes in non-A, non-B hepatitis: Possible masking of viral antigen. Lancet I:1265–1267

    Google Scholar 

  55. Dienstag JL, Krotoski WA, Howard WA, Purcell RH, Neva FA, Galambos JT, Glew RH (1981) Non-A, non-B hepatitis after experimental transmission of malaria by inoculation of blood. J Infect Dis 143:200–209

    Google Scholar 

  56. Dienstag JL, Stevens CE, Szmuness W (1981) The epidemiology on non-A, non-B hepatitis: emerging patterns. In: Gerety RJ (ed): Non-A, non-B hepatitis. Academic Press, New York, pp 119–135

    Google Scholar 

  57. Dieterich DT, Tobias H (1982) The changing spectrum of sporadic hepatitis in high risk groups in New York. Hepatology 2:739

    Google Scholar 

  58. Duermeyer W, Stute R, Hellings JA (1983) An enzymelinked immunosorbent assay for an antigen related to non-A, non-B hepatitis and its antibody: partial characterization of the antigen and chimpanzee transmission. J Med Virol II:11–21

    Google Scholar 

  59. Feinstone SM, Kapikian AZ, Purcell RH, Alter HJ, Holland PV (1975) Transfusion-associated hepatitis not due to viral hepatitis type A or B. New Engl J Med 292:767–770

    Google Scholar 

  60. Feinstone SM, Alter HJ, Dienes HP, Shimizu Y, Popper H, Blackmore D, Sly D, London WT, Purcell RH (1981) Non-A, non-B hepatitis in chimpanzees and marmosets. J Infect Dis 144:588–598

    Google Scholar 

  61. Feinstone SM, Alter HJ, Dienes HP, Purcell RH (1982) Studies on non-A, non-B hepatitis in chimpanzees and marmosets. In: Szmuness W, Alter HJ, Maynard JE (eds) Viral hepatitis: 1981 International Symposium. Franklin Institute Press, Philadelphia, pp 295–304

    Google Scholar 

  62. Feinstone SM, Hoofnagle JH (1984) Non-A, maybe -B hepatitis. New Engl J Med 311:185–189

    Google Scholar 

  63. Galbraith RM, Dienstag JL, Purcell RH, Gower PH, Zuckerman AJ, Williams R (1979) Non-A, non-B hepatitis associated with chronic liver disease in a haemodialysis unit. Lancet I:951–953

    Google Scholar 

  64. Gibo Y, Akahane A, Koike Y, Kiyosawa K, Nagata A, Furuta S (1980) Studies on virus-like particles in human non-A, non-B hepatitis. Hepato-gastroenterol 37: (Suppl) 355

    Google Scholar 

  65. Gibo Y, Nagata A, Kiyosawa K, Furuta S (1981) Intranuclear virus-like particles in the hepatocytes of the patients with non-A, non-B hepatitis. Gastroenterol Jpn 16:576–581

    Google Scholar 

  66. Gmelin K, Kommerell B, Waldherr R, Ehrlich BV (1980) Intranuclear virus-like particles in a case of sporadic non-A, non-B hepatitis. J Med Virol 5:317–322

    Google Scholar 

  67. Grimaud JA, Peyrol S, Vitvitski L, Chevallier-Queyron P, Trep C (1980) Hepatic intranuclear particles in patients with non-A, non-B hepatitis. New Engl J Med 303:818–819

    Google Scholar 

  68. Gust ID, Lehmann NI, Lucas CR, Ferris AA, Locarnini SA (1978) Studies on the epidemiology of hepatitis A in Melbourne. In: Vyas GN, Cohen SN, Schmid R (eds): Viral hepatitis. Franklin Institute Press, Philadelphia, pp 105–112

    Google Scholar 

  69. Hantz O, Vitvitski L, Trepo C (1980) Non-A, non-B hepatitis: identification of hepatitis-B-like virus particles in serum and liver. J Med Virol 5:73–86

    Google Scholar 

  70. Hollinger FB, Gitnick GL, Aach RD, Szmuness W, Mosley JW, Stevens CE, Peters R, Weiner JM, Werch JB, Lander JJ (1978) Non-A, non-B hepatitis transmission in chimpanzees: a project of the transfusion-transmitted viruses study group. Intervirology 10:60–68

    Google Scholar 

  71. Hoofnagle JH (1981) Acute non-A, non-B hepatitis: clinical course and diagnosis. In: Gerety RJ (ed) Non-A, non-B hepatitis. Academic Press, New York, pp 23–36

    Google Scholar 

  72. Hoofnagle JH, Feinstone SM (1981) Serological tests for non-A, non-B hepatitis: controversy. Liver 1:177–182

    Google Scholar 

  73. Hoofnagle JH, Gerety RJ, Tabor E, Feinstone SM, Barker LF, Purcell RH (1977) Transmission of non-A, non-B hepatitis. Ann Int Med 87:14–20

    Google Scholar 

  74. Hopkins R, Kerr A, Field SE, Robertson AE (1983) Particulate structure derived from the serum of a hepatitis non-A, non-B-implicated blood donor. Med Lab Sci 40:77–79

    Google Scholar 

  75. Hruby MA, Schauf V (1978) Transfusion-related short-incubation hepatitis in hemophilic patients. J Amer Med Ass 240:1355–1357

    Google Scholar 

  76. Jackson D, Tabor E, Gerety RJ (1979) Acute non-A, non-B hepatitis: specific ultrastructural alterations in endoplasmic reticulum of infected hepatocytes. Lancet I:1249–1250

    Google Scholar 

  77. Kabiri M, Tabor E, Gerety RJ (1979) Antigen-antibody system associated with non-A, non-B hepatitis detected by indirect immunofluorescence. Lancet II:221–224

    Google Scholar 

  78. Khuroo MS (1980) Study of an epidemic of non-A, non-B hepatitis. Possibility of another human hepatitis virus distinct from post-transfusion non-A, non-B type. Amer J Med 68:818–824

    Google Scholar 

  79. Khuroo MS, Saleem M, Teli MR, Sofi MA (1980) Failure to detect chronic liver disease after epidemic non-A, non-B hepatitis. Lancet II:97–98

    Google Scholar 

  80. Khuroo MS, Teli MR, Skidmore S, Sofi MA, Khuroo MI (1981) Incidence and severity of viral hepatitis in pregnancy. Amer J Med 70:252–255

    Google Scholar 

  81. Kim HC, Saidi P, Ackley AM, Bringelsen KA, Gocke DJ (1980) Prevalence of type B and non-A, non-B hepatitis in hemophilia: relationship to chronic liver disease. Gastroenterology 79:1159–1164

    Google Scholar 

  82. Knodell RG, Conrad ME, Dienstag JL, Bell CJ (1975) Etiological spectrum of post-transfusion hepatitis. Gastroenterology 69:1278–1285

    Google Scholar 

  83. Kobayashi K, Honjo H, Iwata A, Unoura M, Toya D, Makino I, Sawabu N, Hattori N (1982) The correlation of non-A, non-B hepatitis virus with hepatocellular carcinoma. Hepatology 2:157 (Abstr)

    Google Scholar 

  84. Koff RS, Pannuti CS, Pereira ML, Hansson BG, Dienstag JL, Neto VA, Wong DC, Purcell RH (1982) Hepatitis A and non-A, non-B viral hepatitis in Sao Paulo, Brazil: epidemiological, clinical and laboratory comparisons in hospitalized patients. Hepatology 2:445–448

    Google Scholar 

  85. Kryger P, Christoffersen P (1983) Liver histopathology of the hepatitis A virus infection: a comparison with hepatitis type B and non-A, non-B. J Clin Path 36:650–654

    Google Scholar 

  86. MacFarlane TH, Mankikar SD, Buchner BK (1981) Viruslike particles associated with non-A, non-B hepatitis. Transfusion 21:759–760

    Google Scholar 

  87. Marciano-Cabral F, Rublee KL, Carithers RL Jr, Galen EA, Sobieski TH, Cabral GA: Chronic non-A, non-B hepatitis: ultrastructural and serologic studies. Hepatology 1:575–582

  88. Martini GA (1980) Round table discussion: non-A, non-B hepatitis. In: Bianchi L, Gerok W, Sickinger K, Stalder GA (eds): Virus and the Liver. MTP Press, Lancaster, pp 119–127

    Google Scholar 

  89. Mathiesen LR, Skinhoj P, Hardt F, Nielsen JO, Sloth K, Zoffmann H, Moller AM, Wong D, Purcell RH and the Copenhagen Hepatitis Acuta Programme (1979) Epidemiology and clinical characteristics of acute hepatitis types A, B, and non-A, non-B. Scand J Gastroent 14:849–856

    Google Scholar 

  90. Maynard JE, Hadler SC, Francis DP (1983) Epidemiology of non-A/non-B hepatitis. In: Deinhardt F, Deinhardt J (eds) Viral hepatitis. Laboratory and clinical science. M Dekker, New York, pp 231–238

    Google Scholar 

  91. McCaul TF, Tovey G, Tsiquaye KN, Zuckerman AJ (1981) Crystalline arrays and non-A, non-B hepatitis. Lancet II:200

    Google Scholar 

  92. McCaul TF, Tsiquaye KN, Tovey G, Duermeyer W, Zuckerman AJ (1982) Examination of crystalline arrays in non-A, non-B hepatitis. J Med Virol 9:185–188

    Google Scholar 

  93. McCaul TF, Tsiquaye KN, Tovey G, Hames C, Zuckerman AJ (1982) Application of electron microscopy to the study of structural changes in the liver in non-A, non-B hepatitis. J Virol Meth 4:87–106

    Google Scholar 

  94. Meyers JD, Dienstag JL, Purcell RH, Thomas ED, Holmes KK (1977) Parenterally transmitted non-A, non-B hepatitis. Ann Int Med 87:57–59

    Google Scholar 

  95. Mori Y, Ogata S, Ata S, Nakano Y (1980) Virus-like particles associated with non-A, non-B hepatitis. Microbiol Immunol 24:1127–1130

    Google Scholar 

  96. Mori Y, Ogata S, Ata S, Nakano Y (1980) Virus-like particles associated with non-A, non-B hepatitis. Lancet II:318

    Google Scholar 

  97. Mosley JW, Redeker AG, Feinstone SM, Purcell RH (1977) Multiple hepatitis viruses in multiple attacks of acute viral hepatitis. New Engl J Med 296:75–78

    Google Scholar 

  98. Müller R, Willers H, Frösner GG, Gerlich W, Knocke KW, Sipos S, Deicher H, Höpken W (1978) The seroepidemiological pattern of acute viral hepatitis. An epidemiological study on viral hepatitis in the Hannover region. Infection 6:65–70

    Google Scholar 

  99. Myers TJ, Tembrevilla-Zubiri CL, Klatsky AU, Rickles FR (1980) Recurrent acute hepatitis following the use of factor VIII concentrates. Blood 55:748–751

    Google Scholar 

  100. Neurath AR, Stevens CE, Strick N, Szmuness W, Olesko WR, Herley EJ (1980) An antigen detected frequently in human sera with elevated levels of alanine aminotransferase: a potential marker for non-A, non-B hepatitis. J Gen Virol 48:285–295

    Google Scholar 

  101. Norkrans G (1978) Clinical, epidemiological and prognostic aspects of hepatitis A, B, and “non-A, non-B”. Scand J Infect Dis Suppl 17:1–44

    Google Scholar 

  102. Norkrans G, Frösner G, Hermodsson S, Iwarson S (1979) Clinical, epidemiological and prognostic aspects of hepatitis “non-A, non-B” — a comparison with hepatitis A and B. Scand J Infect Dis 11:259–264

    Google Scholar 

  103. Norkrans G, Frösner G, Hermodsson S, Iwarson S (1980) Muldiple hepatitis attacks in drug addicts. J Amer Med Ass 243:1056–1058

    Google Scholar 

  104. Orenstein JM (1983) Ultrastructural markers in AIDS. Lancet II:284–285

    Google Scholar 

  105. Papaevangelou G, Roumeliotou-Karayannis A, Contoyannis P (1982) Changing epidemiological characteristics of acute viral hepatitis in Greece. Infection 10:1–4

    Google Scholar 

  106. Pfeifer U, Thomssen R, Legler K, Böttcher U, Gerlich W, Weinmann E, Klinge O (1980) Experimental non-A, non-B hepatitis: four types of cytoplasmic alteration in hepatocytes of infected chimpanzees. Virchows Arch B Cell Path 33:233–243

    Google Scholar 

  107. Popper H, Dienstag JL, Feinstone S, Alter HJ, Purcell RH (1980) The pathology of viral hepatitis in chimpanzees. Virchows Arch A Path Anat Histol 387:91–106

    Google Scholar 

  108. Popper H, Dienstag JL, Feinstone SM, Alter HJ, Purcell RH (1980) Lessons from the pathology of viral hepatitis in chimpanzees. In: Bianchi L, Gerok W, Sickinger K, Stalder GA (eds) Virus and the Liver. MTP Press, Lancaster, pp 137–150

    Google Scholar 

  109. Poralla T, Hüttenroth TH, Arnold W, Meyer zum Büschenfelde KH (1982) Characterization of circulating immune complexes (CIC) in chronic non-A, non-B (NANB) hepatitis. Liver 2:302

    Google Scholar 

  110. Poralla T, Hüttenroth TH, Arnold W, Dienes HP, Meyer zum Büschenfelde KH (1983) Characterization of circulating immune complexes in chronic non-A, non-B hepatitis. Digestion 28:90–95

    Google Scholar 

  111. Poulsen H (1980) Histopathology of NANB hepatitis. Round table discussion on non-A, non-B hepatitis. In: Bianchi L, Gerok W, Sickinger K, Stalder GA (eds) Virus and Liver. MTP Press, Lancaster, pp 120

    Google Scholar 

  112. Poulsen H, Christoffersen P (1972) Abnormal bile duct epithelium in chronic aggressive hepatitis and cirrhosis. Human Path 3:217–225

    Google Scholar 

  113. Prince AM, Brotman B, Grady GF, Kuhns WJ, Hazzi C, Levine RW, Millian SJ (1974) Long-incubation post-transfusion hepatitis without serological evidence of exposure to hepatitis-B virus. Lancet II:241–246

    Google Scholar 

  114. Prince AM, Brotman B, van den Ende MC, Richardson L, Kellner A (1978) Non-A/non-B hepatitis: identification of a virus-specific antigen and antibody. A preliminary report. In: Vyas GN, Cohen SN, Schmid R (eds) Viral hepatitis. Franklin Institute Press, Philadelphia, pp 633–640

    Google Scholar 

  115. Prince AM, Horowitz B, Brotman B, Huima T, Richardson L, van den Ende MC (1984) Inactivation of hepatitis B and Hutchinson strain non-A, non-B hepatitis viruses by exposure to Tween 80 and ether. Vox Sang 46:36–43

    Google Scholar 

  116. Prince AM, Stephan W, Brotman B (1984) Inactivation of non-A, non-B virus infectivity by a beta-propiolactone/ultraviolet irradiation treatment and aerosil adsorption procedure used for preparation of a stabilized human serum. Vox Sang 46:80–85

    Google Scholar 

  117. Purcell RH, Feinstone SM, Alter HJ, Wong DC (1978) Detection of a novel antigen in two cases of non-A, non-B hepatitis, a recently recognized persistent infection of probable viral origin. In: Stevens JG, Todaro GJ, Fox CF (eds) Persistent viruses. Academic Press, New York, pp 535–549

    Google Scholar 

  118. Renger F, Porst K, Frank KH, Kunze D, Hinkel GK (1981) Ergebnisse zur Epidemiologie, Klinik, Immunologie und Morphologie der non-A/non-B-Hepatitis. Z Ärztl Fortbild 75:894–897

    Google Scholar 

  119. Resnick RH, Stone K, Antonioli D (1983) Primary hepatocellular carcinoma following non-A, non-B posttransfusion hepatitis. Dig Dis Sci 28:908–911

    Google Scholar 

  120. Rugge M, Vanstapel MJ, Realdi G, Tremolada F, Iuzzolino P, Desmet VJ (1982) Aspetti isotologici delle epatiti acute post-transfusionali non-A, non-B. Il Fegato 28:221–227

    Google Scholar 

  121. Rugge M, Vanstapel MJ, Ninfo V, Realdi G, Tremolada F, Montanari PG, van Damme B, Fevery J, De Groote J, Desmet V (1983) Comparative histology of acute hepatitis B and non-A, non-B in Leuven and Padova. Virchows Arch A Path Anat 401:275–288

    Google Scholar 

  122. Schaff Z, Tabor E, Jackson DR, Gerety RJ (1983) AIDS-associated ultrastructural changes: association with hepatitis and other diseases. Lancet I:1336

    Google Scholar 

  123. Scheuer PJ, Teixeira MR, Weller IUD, Murray A, Bamber M, Thomas HC, Sherlock S (1981) Pathology of acute hepatitis A, B, and non-A, non-B. J Path 134:323

    Google Scholar 

  124. Schmid M, Pirovino M, Altorfer J, Gudat F, Bianchi L (1982) Acute hepatitis non-A, non-B; are there any specific light microscopic features? Liver 2:61–67

    Google Scholar 

  125. Seeff LB, Zimmerman HJ, Wright EC, Finkelstein JD, Carcia-Pont P, Greenlee HB, Dietz AA, Leevy CM, Tamburro CH, Schiff ER, Schimmel EM, Zemel R, Zimmon DS, McCollum RW (1977) A randomized double blind controlled trial of the efficacy of immune serum globulin for the prevention of post-transfusion hepatitis. Gastroenterology 72:111–121

    Google Scholar 

  126. Seeff LB, Wright EC, Zimmerman HJ, Hoofnagle JH, dietz AA, Felsher BF, Garcia-Pont PH, Gerety RJ, Greenlee HB, Kiernan T, Leevy CM, Nath N, Schiff ER, Schwartz C, Tabor E, Tamburro C, Vlahcevic Z, Zemel R, Zimmon DS (1978) Posttransfusion hepatitis, 1973–1975: a Veterans Administration cooperativ study. In: Vyas GN, Cohen SN, Schmid R (eds) Viral hepatitis: etiology, epidemiology, pathogenesis and prevention. Franklin Institute Press, Philadelphia, pp 371–381

    Google Scholar 

  127. Shafritz DA, Lieberman HM, Isselbacher KJ, Wands JR (1982) Monoclonal radioimmunoassays for hepatitis B surface antigen: demonstration of hepatitis B virus DNA or related sequences in serum and viral epitopes in immune complexes. Proc Nat Acad Sci USA 79:5675–5679

    Google Scholar 

  128. Shimizu YK, Feinstone SM, Purcell RH, Alter HJ, London WT (1979) Non-A, non-B hepatitis: ultrastructural evidence for two agents in experimentally infected chimpanzees. Science 205:197–200

    Google Scholar 

  129. Shirachi R, Shiraishi H, Tateda A, Kikuchi K, Ishida N (1978) Hepatitis “C” antigen in non-A, non-B post-transfusion hepatitis. Lancet II:853–856

    Google Scholar 

  130. Sidhu GS, Stahll RE, El-Sadr M, Zolla-Pazner S (1983) Ultrastructural markers of AIDS, Lancet I:990–991

    Google Scholar 

  131. Simon N, Mery JP, Trepo CA, Vititski L, Courouce AM (1980) A non-A, non-B hepatitis epidemic in an HB-antigen-free hemodialysis unit: demonstration of serological markers of non-A, non-B virus. Proc Europ Dial Transplant Ass 17:173–178

    Google Scholar 

  132. Skidmore SJ, Jones TE, Boxall EH (1980) Non-A, non-B hepatitis in patients receiving blood products. J Med Virol 6:85–89

    Google Scholar 

  133. Spertini O, Frei PC (1982) Demonstration of a single antigen-antibody system in 26 patients with non-A, non-B viral hepatitis. Lancet II:899–903

    Google Scholar 

  134. Spichtin HP, Gudat F, Schmid M, Pirovino M, Altorfer J, Bianchi L (1982) Microtubular aggregates in human chronic non-A, non-B hepatitis with bridging hepatic necrosis and multinucleated hepatocytic giant cells. Liver 2:355–360

    Google Scholar 

  135. Spichtin HP, Eder G, Gudat F, Krey G, Bianchi L (1983) Ultrastructural alterations in hepatocytes and sinus endothelia in experimental non-A, non-B hepatitis in chimpanzees with and without immunoglobulin prophylaxis. J Med Virol 12:215–226

    Google Scholar 

  136. Spichtin HP, Gudat F, Berthold H, Krey G, Schmid M, Pirovino M, Altorfer J, Stalder G, Eder G, Bianchi L (1984) Nuclear particles of non-A, non-B type in healthy volunteers and patients with hepatitis B. Hepatology 4:510–514

    Google Scholar 

  137. Storch W, Hagert M, Jänisch W, Schwarz KH (1981) Zirkulierende Autoantikörper und Immunkomplexe bei und nach akuter non-A/non-B-Hepatitis. Dtsch Z Verd Stoffw Krankh 41:173–186

    Google Scholar 

  138. Sugg U, Schnaidt M, Schneider W, Lissner R (1980) Clotting factors and non-A, non-B hepatitis. New Engl J Med 303:943

    Google Scholar 

  139. Summers J, Mason WS (1982) Properties of the hepatitis B like viruses related to their taxonomic classification. Hepatology 2:61S-66S

    Google Scholar 

  140. Szmuness W, Stevens CE, Harley EJ, Zang EA, Oleszko WR, William DC, Sadovsky R, Morrison JM, Kellner A (1980) Hepatitis B vaccine. Demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. New Engl J Med 303:833–841

    Google Scholar 

  141. Tabor E (1981) Development and application of the chimpanzee animal model for human non-A, non-B hepatitis. In: Gerety RJ (ed): Non-A, non-B hepatitis. Academic Press, New York, pp 190–205

    Google Scholar 

  142. Tabor E (1983) Animal models, titred inocula, and cell culture systems for the hepatitis A, hepatitis B, and non-A, non-B hepatitis. In: Ouerby LR, Deinhardt F, Deinhardt J (eds): Viral hepatitis: Second International Max von Pettenkofer Symposium. Marcel Dekker, New York, pp 57–59

    Google Scholar 

  143. Tabor E, Gerety RJ (1982) The chimpanzee animal model for non-A, non-B hepatitis: new applications. In: Szmuness W, Alter HJ, Maynard JE (eds) Viral hepatitis: 1981 International Symposium. Franklin Institute Press, Philadelphia, pp 305–317

    Google Scholar 

  144. Tabor E, Gerety RJ, Drucker JA, Seeff LB, Hoofnagle JH, Jackson DR, April M, Barker LF, Pineda-Tamondong G (1978) Transmission of non-A, non-B hepatitis from man to chimpanzee. Lancet I:463–466

    Google Scholar 

  145. Tabor E, Mitchell FD, Goudeau AM, Gerety RJ (1979) Detection of an antigen-antibody system in serum associated with human non-A, non-B hepatitis. J Med Virol 4:161–169

    Google Scholar 

  146. Tabor E, Seeff LB, Gerety RJ (1980) Chronic non-A, non-B hepatitis carrier state: transmissible agent documented in one patient over a six-year period. New Engl J Med 303:140–143

    Google Scholar 

  147. Tateda A, Kikuchi K, Numazaki Y, Shirachi R, Ishida N (1979) Non-B hepatitis in Japanese recipients of blood transfusions: Clinical and serologic studies after the introduction of laboratory screening of donor blood for hepatitis B surface antigen. J Infect Dis 139:511–518

    Google Scholar 

  148. Thomas HC, Karayiannis P, Bamber M, Luo K, Sherlock S (1982) An immunoradiometric assay for the detection of an antigen/antibody system associated with non-A, non-B hepatitis: prevalence of Ag/Ab in acute and chronic liver disease and “high-risk” hepatitis groups. Hepatology 2:748

    Google Scholar 

  149. Thorne CH, Higgins GR, Gitnick GL, Lewin KJ (1981) Chronic active hepatitis: non-A, non-B verus type B. Lab Invest 44:66A

    Google Scholar 

  150. Thorne CH, Higgins GR, Ulich TR, Gitnick GL, Lewin KJ (1982) A histologic comparison of hepatitis B with non-A, non-B chronic active hepatitis. Arch Path Lab Med 106:433–436

    Google Scholar 

  151. Tong MJ, Thursby M, Rakela J, Mc Peak C, Edwards VM, Mosley JW (1981) Studies on maternal-infant transmission of the viruses which cause acute hepatitis. Gastroenterology 80:999–1004

    Google Scholar 

  152. Trepo C, Vitvitski L, Hantz O, Chevallier P, Grimaud JA, Pichoud C, Sepetjan M (1980) Identification and detection of viral specific core and e Ag/Ab systems cross reacting with those of hepatitis B in non-A, non-B hepatitis (NANB/H). Gastroenterology 79:1060

    Google Scholar 

  153. Trepo C, Vitvitski L, Hantz O, Chevallier P, Pichoud C, Babin S, Grimaud JA, Sepetjan M (1980) Identifikation and detection of long incubation non-A, non-B hepatitis virus and associated antigens or antibodies. J Virol Meth 2:127–139

    Google Scholar 

  154. Trepo C, Vitvitski L, Hantz O, Chevallier P, Lehman H, Schlaak M, Sepetjan M (1981) Detection by immunofluorescence of a new “core-like” AG/Ab system in liver and serum of patients with NANB hepatitis. Liver 1:191–200

    Google Scholar 

  155. Tsiquaye KN, Zuckerman AJ (1979) New human hepatitis virus. Lancet I:1135–1136

    Google Scholar 

  156. Tsiquaye KN, Bird RG, Tovey G, Wyke J, Williams R, Zuckerman AJ (1980) Further evidence of cellular changes associated with non-A, non-B hepatitis. J Med Virol 5:63–71

    Google Scholar 

  157. Tsiquaye KN, Amini S, Kessler H, Bird RG, Tovey G, Zuckerman AJ (1981) Ultrastructural changes in the liver in experimental non-A, non-B hepatitis. Brit J Exp Path 62:41–51

    Google Scholar 

  158. Visona KA, Villarejos VM, Mosley JW (1982) Antigenantibody system on non-A, non-B hepatitis. Gastroenterology 82:1249

    Google Scholar 

  159. Vitvitski L, Trepo C, Prince AM, Brotman B (1979) Detection of virus-associated antigen in serum and liver of patients with non-A, non-B hepatitis. Lancet II:1263–1267

    Google Scholar 

  160. Wands JR (1983) Non-A, non-B hepatitis. Hepatology 3:764–766

    Google Scholar 

  161. Wands JR, Lieberman HM, Muchmore E, Isselbacher K, Shafritz DA (1982) Detection and transmission in chimpanzees of hepatitis B virus-related agents formerly designatet “non-A, non-B” hepatitis. Proc Nat Acad Sci USA 79:7552–7556

    Google Scholar 

  162. Wands JR, Marciniak RA, Isselbacher KJ, Varghese M, Don G, Halliday JW, Powell LW (1982) Demonstration of previously undetected hepatitis B viral determinants in an Australian aboriginal population by monoclonal anti-HBs antibody radioimmunoassays. Lancet I:977–980

    Google Scholar 

  163. Wands JR, Bruns RR, Carlson RI, Ware A, Menitove JE, Isselbacher KJ (1982) Monoclonal IgM radioimmunoassay for hepatitis B surface antigen: high binding activity in serum that is unreactive conventional antibodies. Proc Nat Acad Sci USA 79:1277–1281

    Google Scholar 

  164. Widmer UK, Villaverde A, Grob PJ (1980) Hepatitisepidemiologie 1977–1979. Schweiz Med Wochenschr 110:930–937, 978–984

    Google Scholar 

  165. Wong DC, Purcell RH, Sreenivasan MA, Prasad SR, Pavri KM (1980) Epidemic and endemic hepatitis in India: Evidence for a non-A, non-B hepatitis virus aetiology. Lancet II:876–879

    Google Scholar 

  166. Woronow DI, Sampliner RE, Alter MJ, Smallwood LA, Tabor E, Gerety RJ (1981) Clinical characteristics of sporadic acute non-A, non-B hepatitis. Gastroenterology 80:1354

    Google Scholar 

  167. Wyke RJ, Tsiquaye KN, Thornton A, White Y, Portmann B, Das PK, Zuckerman AJ, Williams R (1979) Transmission of non-A, non-B hepatitis to chimpanzees by factor-IX concentrates after fatal complications in patients with chronic liver disease. Lancet I:520–524

    Google Scholar 

  168. Yoshizawa H, Akahane Y, Itoh Y, Iwakiri S, Kitajima K, Morita M, Tanaka A, Nojiri T, Shimizu M, Miyakawa Y, Mayumi M (1980) Viruslike particles in a plasma fraction (fibrinogen) and in the circulation of apparently healthy blood donors capable of inducing non-A/non-B hepatitis in humans and chimpanzees. Gastroenterology 79:512–520

    Google Scholar 

  169. Yoshizawa H, Itoh Y, Iwakiri S, Kitajima K, Tanaka A, Nojiri T, Miyakawa Y, Mayumi M (1981) Demonstration of two different types of non-A, non-B hepatitis by reinjection and cross-challenge studies in chimpanzees. Gastroenterology 81:107–113

    Google Scholar 

  170. Yoshizawa H, Itoh Y, Iwakiri S, Kitajima K, Tanaka A, Tachibana T, Nakamura T, Miyakawa Y, Mayumi M (1982) Non-A, non-B (type I) hepatitis agent capable of inducing tubular ultrastructures in the hepatocyte cytoplasm of chimpanzees: inactivation by formalin and heat. Gastroenterology 82:502–506

    Google Scholar 

  171. Yoshizawa H, Itoh Y, Iwakiri S, Kitajima K, Noguchi Y, Tachibana K, Nakamura T, Miyakawa Y, Mayumi M (1984) Beta-propiolactone for the inactivation of non-A/non-B type I hepatitis virus capable of inducing cytoplasmic tubular ultrastructures in chimpanzees. Vox Sang 46:86–91

    Google Scholar 

  172. Prince AM, Huima T, Williams BAA, Bardina L, Brotman B (1984) Isolation of a virus from chimpanzee liver cell cultures inoculated with sera containing the agent of non-A, non-B hepatitis. Lancet II:1071–1075

    Google Scholar 

  173. Stevens CE, Aach RD, Hollinger FB, Mosley JW, Szmuness W, Kahn R, Werch J, Edwards V (1984) Hepatitis B virus antibody in blood donors and the occurrence of non-A, non-B hepatitis in transfusion recipients. Ann Intern Med 101:733–738

    Google Scholar 

  174. Seto B, Coleman W, Iwarson S, Gerety RJ (1984) Detection of reverse transcriptase activity in association with the non-A, non-B hepatitis agent(s). Lancet II:941–943

    Google Scholar 

  175. Iwarson S, Schaff Z, Mitchell F, Gerety RJ (1985) Non-A, non-B hepatitis virus. Lancet I:171

    Google Scholar 

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Spichtin, H.P. Hepatitis non-A, non-B (HNANB): Epidemiologische, klinische, serologische und morphologische Aspekte. Klin Wochenschr 63, 389–404 (1985). https://doi.org/10.1007/BF01733664

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