Digestive Diseases and Sciences

, Volume 38, Issue 4, pp 577–593 | Cite as

Interferon in the management of chronic hepatitis B

  • Robert P. Perrillo
Review Article

Abstract

Many drugs have been used in the treatment of chronic hepatitis B, but with the exception of interferon, none have proved to be effective. Several studies have found that a sustained loss of viral replication occurs in approximately 40% of patients who arted with a 16-week course of recombinant interferon alfa-2b given in a dose of 5 million units daily or 10 million units three times weekly. Moreover, disappearance of hepatitis B surface antigen in serum has been observed in 10–15% of treated patients. Based on these results, the Food and Drug Administration approved the use of this form of interferon in chronic hepatitis B in July 1992. This article reviews the importance of chronic hepatitis B as a health problem as well as the mechanisms of action, benefits, and adverse effects associated with interferon. Particular emphasis is given to the safety and efficacy data for recombinant interferon alfa-2b.

Key Words

interferon antiviral hepatitis B hepatitis B virus 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Centers for Disease Control: Hepatitis Surveillance. Report number 53, December, 1990Google Scholar
  2. 2.
    CDC: Protection against viral hepatitis. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 39:1–26, 1990Google Scholar
  3. 3.
    Szmuness W, Harley EJ, Ikram H, Stevens CE: Sociodemographic aspects of the epidemiology of hepatitis B.In Viral Hepatitis. Etiology, Epidemiology, Pathogenesis and Prevention. GN Vyas, SN Cohen, R Schmid (eds). Philadelphia, Franklin Institute Press, 1978, pp 297–320Google Scholar
  4. 4.
    Williams WW, Hickson MA, Kane MA, Kendal AP, Spika JS, Hinman AR: Immunization policies and vaccine coverage among adults: the risk for missed opportunities. Ann Intern Med 108:616–625, 1988Google Scholar
  5. 5.
    Beasley RP: Hepatitis B virus as the etiologic agent in hepatocellular carcinoma-epidemiologic considerations. Hepatology 2:215–265, 1982Google Scholar
  6. 6.
    Feinman SV, Berris B, Cootner N, Sinclair JC, Wrobel DM: Results of a long-term prospective study of the hepatitis B surface antigen (HBsAg) carrier state. Hepato-Gastroenterol 29:58–61, 1982Google Scholar
  7. 7.
    Sampliner RE, Hamilton FA, Iseri OA, Tabor E, Boitnott J: The liver histology and frequency of clearance of the hepatitis B surface antigen (HBsAg) in chronic carriers. Am J Med Sci 277:17–22, 1979Google Scholar
  8. 8.
    Dudley FJ, Scheuer PJ, Sherlock S: Natural history of hepatitis associated antigen-positive chronic liver disease. Lancet 2:1388–1393, 1972Google Scholar
  9. 9.
    Weissberg JI, Andres LL, Smith CL, Weick S, Nichols JE, Garcia G, Robinson WS, Merigan TC, Gregory PB: Survival in chronic hepatitis. An analysis of 379 patients. Ann Intern Med 101:613–616, 1984Google Scholar
  10. 10.
    Perrillo RP, Schiff ER, Davis GL, Bodenheimer HC, Lindsay K, Dienstag JL, O'Brien C, Tamburro C, Jacobson IM, Sampliner R, Feit D, Lefkowitch J, Kuhns M, Meschievitz C, Sanghvi B, Albrecht J, Gibas A: A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal, in the treatment of chronic hepatitis B. N Engl J Med 323:295–301, 1990Google Scholar
  11. 11.
    Liaw YF, Tai D-I, Chuc C-M, Chen T-J: The development of cirrhosis in patients with chronic type hepatitis: A prospective study. Hepatology 8:493–496, 1988Google Scholar
  12. 12.
    Beasley RP, Hwang LY: Epidemiology of hepatocellular carcinoma.In Viral Hepatitis and Liver Disease. GN Vyas, JL Dienstag, JH Hoofnagle (eds). New York, Grune & Stratton, 1984, pp 209–224Google Scholar
  13. 13.
    McMahon BJ, Alberts SR, Wainwright RB, Bulkow L, Lanier AP: Hepatitis B-related sequelae: prospective study in 1400 hepatitis B surface antigen-positive Alaska native carriers. Arch Intern Med 150:1051–1054, 1990Google Scholar
  14. 14.
    Hall AJ, Alveyn CG, Winter PD, Wright R: Mortality of hepatitis B-positive blood donors in England and Wales.In Viral Hepatitis and Liver Disease. AJ Zuckerman (ed). New York, Alan R. Liss, 1988, pp 192–194Google Scholar
  15. 15.
    Todo S, Demetris AJ, Van Thiel D, Teperman L, Fung JJ, Starzl T: Orthotopic liver transplantation for patients with hepatitis B virus-related liver disease. Hepatology 13:619–626, 1991Google Scholar
  16. 16.
    O'Grady JG, Williams R: Liver transplantation for viral hepatitis. Br Med Bull 46:481–491, 1990Google Scholar
  17. 17.
    Szmuness W, Prince AM, Hirsch RL, Brotman B: Familial clustering of hepatitis B infections. N Engl J Med 289:1162–1166, 1973Google Scholar
  18. 18.
    Perrillo RP, Gelb L, Campbell C, Wellinghoff W, Ellis FR, Overby L, Aach RD: Hepatitis B e antigen, DNA polymerase activity, and infection of household contacts with hepatitis B virus. Gastroenterology 76:1319–1325, 1979Google Scholar
  19. 19.
    Bernier RH, Sampliner R, Gerety R, Tabor E, Hamilton F, Nathanson N: Hepatitis B infection in households of chronic carriers of hepatitis B surface antigen. Factors associated with prevalence of infection. Am J Epidemiol 116:199–211, 1982Google Scholar
  20. 20.
    Margolis HS, Alter MJ, Hadler SC: Hepatitis B: Evolving epidemiology and implications for control. Semin Liv Dis 11:84–92, 1991Google Scholar
  21. 21.
    Hoofnagle JH, Seeff LB: Natural history of chronic type B hepatitis. Prog Liver Dis 7:469–479, 1982Google Scholar
  22. 22.
    Di Bisceglie AM: Hepatocellular carcinoma. Ann Intern Med 108:390–401, 1988Google Scholar
  23. 23.
    Fattovich G, Brollo L, Alberti A, Giustina G, Pontisso P, Realdi G, Ruol A: Chronic persistent hepatitis type B can be a progressive disease when associated with sustained virus replication. J Hepatol 11:29–33, 1990Google Scholar
  24. 24.
    Chadwick RG, Galizzi J, Heathcote J, Lyssiotis T, Cohen BJ, Scheuer PJ, Sherlock S: Chronic persistent hepatitis: Hepatitis B virus markers and histological follow up. Gut 20:372–377, 1979Google Scholar
  25. 25.
    Hoofnagle JH, Shafritz DA, Popper H: Chronic type B hepatitis and the “healthy” HBsAg carrier state. Hepatology 7:758–763, 1987Google Scholar
  26. 26.
    Perrillo RP, Campbell CR, Sanders GE, Regenstein FG, Bodicky CJ: Spontaneous clearance and reactivation of hepatitis B virus infection among male homosexuals with chronic type B hepatitis. Ann Intern Med 100:43–46, 1984Google Scholar
  27. 27.
    Davis GL, Hoofnagle JH, Waggoner JG: Spontaneous reactivation of chronic hepatitis B virus infection. Gastroenterology 86:230–235, 1984Google Scholar
  28. 28.
    A Trial Group of the European Association for the Study of the Liver: Steroids in chronic B hepatitis. A randomized, double-blind, multinational trial on the effect of low-dose, long term treatment on survival. Liver 6:227–232, 1986Google Scholar
  29. 29.
    Realdi G, Alberti A, Rugge M, Bortolotti F, Rigoli AM, Tremolada F, Ruol A: Seroconversion from hepatitis B e antigen to anti-HBe in chronic hepatitis B virus infection. Gastroenterology 79:195–199, 1980Google Scholar
  30. 30.
    Peters M, Vierling J, Gershwin ME, Milich D, Chisari FV, Hoofnagle JH: Immunology and the liver. Hepatology 13:977–994, 1991Google Scholar
  31. 31.
    Abb J, Zachoval R, Eisenburg J, Pape GR, Zachoval V, Deinhardt F: Production of interferon alpha and interferon gamma by peripheral blood leukocytes from patients with chronic hepatitis B virus infection. J Med Virol 16:171–176, 1985Google Scholar
  32. 32.
    Jicha DL, Davis GL, Peters MG, Hoofnagle JH, Jones EA: Effects of recombinant human leukocyte interferon treatment on endogeneous interfeon production in patients with chronic type B hepatitis. J Interferon Res 6:13–20, 1986Google Scholar
  33. 33.
    Ikeda T, Pignatelli M, Lever AML, Thomas HC: Relationship of HLA protein display to activation of 2-5A synthetase in HBe antigen or anti-HBe positive chronic HBV infection. Gut 27:1498–1501, 1986Google Scholar
  34. 34.
    Mondelli MG, Mieli-Vergani G, Alberti A, Vergani B, Portmann B, Eddleston ALWF, 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 129:2773–2781, 1982Google Scholar
  35. 35.
    Montano L, Miescher GC, Goodhall AH, Wiedmann KH, Janossy G, Thomas HC: Hepatitis B virus and HLA antigen display in the liver during chronic hepatitis B virus infection. Hepatology 2:557–561, 1982Google Scholar
  36. 36.
    Eddleston ALWF: Immunological aspects of hepatitis B infection.In Viral Hepatitis and Liver Disease. AJ Zuckerman (ed). New York: Alan R. Liss, 1988, pp 603–605Google Scholar
  37. 37.
    Pasquinelli C, Laure F, Chatenoud L, Beaurin G, Gazengal C, Bismuth H, Degos F, Tiollais P, Bach JF, Brechot C: Hepatitis B virus DNA in mononuclear blood cells. J Hepatol 3:95–103, 1986Google Scholar
  38. 38.
    Peters M, Davis GL, Dooley JS, Hoofnagle JH: The interferon system in acute and chronic viral hepatitis. Prog Liver Dis 89:453–468, 1986Google Scholar
  39. 39.
    Kirchner H: Interferons, a group of multiple lymphokines. Springer Semin Immunopathol 7:347–374, 1984Google Scholar
  40. 40.
    Peters M: Mechanisms of action of interferons. Semin Liver Dis 9:235–239, 1989Google Scholar
  41. 41.
    Armstrong RW, Gurwith MJ, Waddell D, Merigan TC: Cutaneous interferon production in patients with Hodgkin's disease and other cancers interferon with Varicella or Vaccinia. N Engl J Med 283:1182–1187, 1970Google Scholar
  42. 42.
    Stewart WE: The Interferon System, 2nd ed. New York, Springer-Verlag, 1979Google Scholar
  43. 43.
    Gresser I, Tovey MG, Bandu M-T, Maury C, Brouty-Boye D: Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. I. Rapid evolution of encephalomyocarditis virus infection. J Exp Med 144:1305–1315, 1976Google Scholar
  44. 44.
    Gresser I, Tovey MG, Maury C, Bandu M-T: Role of inteferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. II. Studies with herpes simplex, Maloney sarcoma, vesiculostomatitis, Newcastle disease and influenza viruses. J Exp Med 144:1316–1323, 1976Google Scholar
  45. 45.
    Samuel CE: The interferon-induced protein P1/eIF-2 alpha kinase.In The Interferon System: A Current Review to 1987. S Baron, GJ Stanton, WR Fleischmann (eds). Austin, University of Texas Press, 1987, pp 373–381Google Scholar
  46. 46.
    Peters M: Immunological aspects of antiviral therapy. Springer Semin Immunopathol 12:47–56, 1990Google Scholar
  47. 47.
    Pignatelli M, Waters J, Brown D, Lever A, Iwarson S, Schaff Z, Gerety R, Thomas HC: HLA class I antigens on the hepatocyte membrane during recovery from acute hepatitis B virus infection and during interferon therapy in chronic hepatitis B virus infection. Hepatology 6:349–353, 1986Google Scholar
  48. 48.
    Chu CM, Shyu WC, Kuo RY, Liaw YF: HLA class I antigen display on hepatocyte membrane in chronic hepatitis B virus infection: Its role in the pathogenesis of chronic type B hepatitis. Hepatology 6:1311–1316, 1987Google Scholar
  49. 49.
    Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC: Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329:506–512, 1987Google Scholar
  50. 50.
    Chen L, Mathieu-Mahul D, Bach FH, Dausset J, Bensussan A, Sasportes M: Recombinant interferon alpha can induce rearrangement of T cell antigen receptor alpha genes and maturation in cytotoxicity in T lymphocyte clonesin vitro. Proc Natl Acad Sci USA 83:4887–4889, 1986Google Scholar
  51. 51.
    Daniels HM, Meager A, Eddleston ALWF, Alexander GJM, Williams R: Spontaneous production of tumor necrosis factor alpha and interleukin-1 beta during interferon alpha treatment of chronic HBV infection. Lancet 335:875–877, 1990Google Scholar
  52. 52.
    Billiau A: The mode of action of interferons in viral infections and their possible role in the control of hepatitis B. J Hepatol 3(suppl 2):S171-S179, 1986Google Scholar
  53. 53.
    Castilla A, Prieto J, Fausto N: Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy. N Engl J Med 324:933–940, 1991Google Scholar
  54. 54.
    Brook MG, McNamara AL, Perrillo RP, Cabal CM, Campbell CR: Quantitation of hepatitis B viral DNA by solution hybridization: Comparison with DNA polymerase and hepatitis B e antigen during antiviral therapy. J Med Virol 27:274–281, 1989Google Scholar
  55. 55.
    Brook MG, Petrovic L, McDonald JA, Scheuer PJ, Thomas HC: Histological improvement after anti-viral treatment for chronic hepatitis B virus infection. J Hepatol 8:218–225, 1989Google Scholar
  56. 56.
    Di Bisceglie AM, Waggoner JG, Hoofnagle JH: Hepatitis B virus deoxyribonucleic acid in liver of chronic carriers. Correlation with serum markers and changes associated with loss of hepatitis B e antigen after viral therapy. Gastroenterology 93:1236–1241, 1987Google Scholar
  57. 57.
    Lok ASF, Ma OCK, Lau JYN: Interferon alfa therapy in patients with chronic hepatitis B virus infection. Effects on hepatitis B virus DNA in the liver. Gastroenterology 100:756–761, 1991Google Scholar
  58. 58.
    Shafritz DA, Shouval D, Sherman HI, Hadziyannis SJ, Kew MC: Integration of hepatitis B virus DNA into the genome of liver cells in chronic liver disease and hepatocellular carcinoma. Studies in percutaneous liver biopsies and post-mortem tissue tissue specimens. N Engl J Med 305:1067–1073, 1981Google Scholar
  59. 59.
    Caselmann WH, Eisenburg J, Hofschneider PH, Koshy R: Beta and gamma interferon chronic active hepatitis B. A pilot trial of short-term combination therapy. Gastroenterology 96:449–455, 1981Google Scholar
  60. 60.
    Scullard GH, Pollard RB, Smith JL, Sacks GL, Gregory PB, Robinson WS, Merigan TC: Antiviral treatment of chronic hepatitis B virus infection. I. Changes in viral markers with interferon combined with adenine arabinoside. J Infect Dis 143:772–783, 1981Google Scholar
  61. 61.
    Brook MG, Karayiannis P, Thomas HC: Which patients with chronic hepatitis B virus infection will respond to alpha interferon therapy? A statistical analysis of predictive factors. Hepatology 10:761–763, 1989Google Scholar
  62. 62.
    Lok ASF, Lai CL, Wu PC, Lau JYN, Leung EKY, Wong LSK, Fung YL: Alpha interferon treatment in Chinese patients with chronic hepatitis B. J Hepatol 11:S121-S125, 1990Google Scholar
  63. 63.
    Perrillo RP, Regenstein FG, Peters MG, DeSchryver-Kecskemeti K, Bodicky CJ, Campbell CR, Kuhns MC: Prednisone withdrawal followed by recombinant alpha interferon in the treatment of chronic type B hepatitis. A randomized, controlled trial. Ann Intern Med 109:95–100, 1988Google Scholar
  64. 64.
    Novick DM, Lok ASF, Thomas HC: Diminished responsiveness of homosexual men to antiviral therapy for HBsAg-positive chronic liver disease. J Hepatol 1:29–35, 1984Google Scholar
  65. 65.
    McDonald JA, Caruso L, Karayiannis P, Scully LJ, Harris JRW, Forster GE, Thomas HC: Diminished responsiveness of male homosexual chronic hepatitis B virus carriers with HTLV-III antibodies to recombinant alpha interferon. Hepatology 7:719–723, 1987Google Scholar
  66. 66.
    Roonbloom LE, Alm GV, Oberg KE: Autoimmunity after alpha-interferon therapy for malignant carcinoid tumors. Ann Intern Med 115:178–183, 1991Google Scholar
  67. 67.
    Conlon KC, Urba WJ, Smith JW, Steis RG, Longo DL, Clark JW: Exacerbation of symptoms of autoimmune disease in patients receiving alpha-interferon therapy. Cancer 65:2237–2242, 1990Google Scholar
  68. 68.
    Greenberg HBV, Pollard RB, Lutwick LI, Gregory PB, Robinson WS, Merigan TC: Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis. N Engl J Med 295:517–522, 1976Google Scholar
  69. 69.
    Perrillo RP: Treatment of chronic hepatitis B with interferon: Experience in Western countries. Semin Liver Dis 9:240–248, 1989Google Scholar
  70. 70.
    Katkov WN, Dienstag JL: Prevention and therapy of viral hepatitis. Semin Liver Dis 11:165–174, 1991Google Scholar
  71. 71.
    Seeff LB, Koff RS: Evolving concepts of the clinical and serologic consequences of hepatitis B virus infection. Semin Liver Dis 6:11–22, 1986Google Scholar
  72. 72.
    Davis GFL, Hoofnagle JH: Interferon in viral hepatitis: Role in pathogenesis and treatment. Hepatology 6:1038–1041, 1986Google Scholar
  73. 73.
    Hoofnagle JH, Peters M, Mullen KD, Jones DB, Rustgi V, Di Bisceglie A, Hallahan C, Park Y, Meschievitz C, Jones EA: Randomized, controlled trial of recombinant human alpha interferon patients with chronic hepatitis B. Gastroenterology 95:1318–1325, 1988Google Scholar
  74. 74.
    Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J: Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1:431–435, 1981Google Scholar
  75. 75.
    Fevery J, Elewaut A, Michielsen P, Nevens F, Van Eyken P, Adler M, Desmet V: Efficacy of interferon alfa-2b with or without prednisone withdrawal in the treatment of chronic viral hepatitis B. A prospective double-blind Belgian-Dutch study. J Hepatol 11:S108-S112, 1990Google Scholar
  76. 76.
    Perez V, Tanno H, Villamil F, Fay O: Recombinant interferon alfa-2b following prednisone withdrawal in the treatment of chronic type B hepatitis. J Hepatol 11:S121-S125, 1990Google Scholar
  77. 77.
    Muller R, Baumgarten R, Markus R, Schulz M, Wittenberg H, Hintsche-Kilger B, Fengler JD, Von Wussow P, Meisel H, Klein H, Malmus K, Schmidt FW: Treatment of chronic hepatitis B with interferon alfa-2b. J Hepatol 11:S137-S140, 1990Google Scholar
  78. 78.
    Waked I, Amin M, El Fattah SA, Osman LM, Sabbour MS: Experience with interferon in chronic hepatitis B in Egypt. J Chemother 2:310–318, 1990Google Scholar
  79. 79.
    Lok ASF, Wu PC, Lai CL, Lau JYN, Leung EKY, Wong LSK, Ma OCK, Lauder IJ, Ng CPL, Chung HT: A controlled trial of interferon with or without prednisone priming for chronic hepatitis B. Gastroenterology 102:2091–2097, 1992Google Scholar
  80. 80.
    Di Bisceglie AM, Bergasa NV, Fong TL, Fried MW, Swain M, Baker B, Korenman J, Waggoner JG, Park Y, Hoofnagle JH: Randomized, controlled trial of recombinant alpha interferon therapy for chronic hepatitis B. Hepatology 13:70A, 1991 (abstract)Google Scholar
  81. 81.
    Ruiz-Moreno M, Rua MJ, Molina J, Moraleda G, Moreno A, Aguado JG, Carreno V: Prospective, randomized controlled trial of interferon alpha in children with chronic hepatitis B. Hepatology 13:1035–1039, 1991Google Scholar
  82. 82.
    Scullard GH, Smith CU, Merigan TC, Robinson WS, Gregory PB: Effects of immunosuppressive therapy on viral markers in chronic active hepatitis B. Gastroenterology 81:987–991, 1981Google Scholar
  83. 83.
    Rakela J, Redeker AG, Weliky B: Effect of short-term prednisone therapy on aminotransferase levels and hepatitis B virus markers in chronic type B hepatitis. Gastroenterology 84:956–960, 1983Google Scholar
  84. 84.
    Perrillo RP, Regenstein FG, Bodicky CJ, Campbell CR, Sanders GE, Sunwoo YC: Comparative efficacy of adenine arabinoside 5′-monophosphate and prednisone withdrawal followed by adenine arabinoside 5′-monophosphate in the treatment of chronic active hepatitis type B. Gastroenterology 88:780–786, 1985Google Scholar
  85. 85.
    Yokosuka O, Omata M, Imazeki F, Hirota K, Mora J, Uchiumi K, Ito Y, Okuda K: Combination of short-term prednisolone and adenine arabinoside in the treatment of chronic hepatitis B. Gastroenterology 89:246–251, 1985Google Scholar
  86. 86.
    Omata M, Imazeki F, Yokosuka O, Ito Y, Uchiumi K, Mori J, Okuda K: Recombinant leukocyte A interferon treatment in patients with chronic hepatitis B virus infection. Pharmacokinetics, tolerance and biologic effects. Gastroenterology 88:870–880, 1985Google Scholar
  87. 87.
    Sagnelli E, Maio G, Felaco GM, Izzo CM, Manzillo G, Pasquale G, Filippini P, Piccinino F: Serum levels of hepatitis B surface and core antigens during immunosuppressive treatment of HBsAg-positive chronic active hepatitis. Lancet 2:395–397, 1980Google Scholar
  88. 88.
    Perrillo RP, Regenstein FG: Corticosteroid therapy for chronic active hepatitis B: Is a little too much? Hepatology 6:1416–1418, 1986 (editorial)Google Scholar
  89. 89.
    Nair PV, Tong MJ, Stevenson D, Roskamp D, Boone C: Effects of short-term, high-dose prednisone treatment of patients with HBsAg-positive chronic active hepatitis. Liver 5:8–12, 1985Google Scholar
  90. 90.
    Hess GH, Manns M, Hutteroth TH, Meyer zum Buschenfelde KH: Discontinuation of immunosuppressive therapy in hepatitis B surface antigen-positive chronic hepatitis: Effect on viral replication and liver cell damage. Digestion 36:47–54, 1987Google Scholar
  91. 91.
    Renault PF, Hoofnagle JH: Side effects of alpha interferon. Semin Liver Dis 9:273–277, 1989Google Scholar
  92. 92.
    Renault PF, Hoofnagle JH, Park Y, Mullen KD, Peters M, Brian-Jones D, Rustgi V, Jones EA: Psychiatric complications of long-term interferon alfa therapy. Arch Intern Med 147:1577–1580, 1987Google Scholar
  93. 93.
    McDonald EM, Mann AH, Thomas HC: Interferons as mediators of psychiatric morbidity. An investigation in a trial of recombinant gamma interferon in hepatitis B carriers. Lancet 2:1175–1177, 1987Google Scholar
  94. 94.
    Perrillo RP: Treatment of chronic hepatitis B.In Viral Hepatitis and Liver Disease. FB Hollinger, SM Lemon, HS Margolis (eds). Baltimore, William and Wilkins, 1991, pp 616–623Google Scholar
  95. 95.
    Mayet WJ, Hess G, Gerken G, Rossol S, Voth R, Manns M, Meyer zum Buschenfelde KH: Treatment of chronic type B hepatitis with recombinant alpha interferon induces autoantibodies not specific for autoimmune chronic hepatitis. Hepatology 10:24–28, 1989Google Scholar
  96. 96.
    Burman P, Karlsson FA, Oberg K: Autoimmune thyroid disease in interferon treated patients. Lancet 2:100–101, 1985Google Scholar
  97. 97.
    Craxi A, Di Marco V, Volpes R, Palazzao U: Anti-alpha interferon antibodies after alpha interferon treatment in patients with chronic viral hepatitis. Hepato-Gastroenterol 35:304–305, 1988Google Scholar
  98. 98.
    Porres JC, Carreno V, Ruiz M, Marron JA, Bartolome J: Interferon antibodies in patients with chronic HBV infection treated with recombinant interferon. J Hepatol 8:351–357, 1989Google Scholar
  99. 99.
    Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC, Perrillo RP, Carey W, Jacobson IM, Payne J, Dienstag J, Van Thiel DH, Tamburro C, Lefkowitch J, Albrecht J, Meschievitz C, Ortego TJ, Gibas A: Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. N Engl J Med 321:1501–1506, 1989Google Scholar
  100. 100.
    Lok ASF, Lai CL, Leung EKY: Interferon antibodies may negate the antiviral effects of recombinant alpha interferon treatment in patients with chronic hepatitis B virus infection. Hepatology 12:1266–1270, 1990Google Scholar
  101. 101.
    Williams SJ, Farrell GC: Inhibition of antipyrine metabolism by interferon. Br J Clin Pharmacol 22:610–612, 1986Google Scholar
  102. 102.
    Williams SJ, Baird-Lambert JA, Farrell CGC: Inhibition of theophylline metabolism by interferon. Lancet 2:939–941, 1987Google Scholar
  103. 103.
    Korenman J, Baker B, Waggoner J, Everhart JE, Di Bisceglie AM, Hoofnagle JH: Long-term remission of chronic hepatitis B after alpha-interferon therapy. Ann Intern Med 114:629–634, 1991Google Scholar
  104. 104.
    Perrillo RP, Brunt EM: Hepatic histologic and immunohistochemical changes in chronic hepatitis B after prolonged clearance of hepatitis B e antigen and hepatitis B surface antigen. Ann Intern Med 115:113–115, 1991Google Scholar
  105. 105.
    Karayiannis P, Kanatakis S, Thomas HC: Anti-HBs response in seroconverting chronic HBV carriers following alpha-interferon treatment. J Hepatol 10:350–352, 1990Google Scholar
  106. 106.
    Chung HT, Lok ASF, Lin HJ, Lai CL: Hepatitis B virus DNA using polymerase chain reaction in sera of chronic hepatitis B patients treated with alpha interferon.In Proceedings of the 1990 International Symposium on Viral hepatitis and Liver Disease, p 129 (abstract)Google Scholar
  107. 107.
    Kuhns M, McNamara A, Mason A, Campbell C, Perrillo R: Serum and liver hepatitis B virus DNA in chronic hepatitis B after sustained loss of surface antigen. Gastroenterology 103:1649–1656, 1992Google Scholar
  108. 108.
    Fong T-L, Di Bisceglie AM, Feinstone SM, Waggoner JG, Axiotis CA, Hoofnagle JH: Persistent hepatitic HBV-DNA after clearance of HBsAg from serum of patients with chronic Hepatitis B. Hepatology 14:130A, 1991 (abstract)Google Scholar
  109. 109.
    Brunetto MR, Oliveri F, Rocca G, Criscuolo D, Chiaberge E, Capalbo M, David E, Verme G, Bonino F: Natural course and response to interferon of chronic hepatitis B accompanied by antibody to hepatitis B e antigen. Hepatology 10:198–202, 1989Google Scholar
  110. 110.
    Rosina F, Garripoli A, Lattore V, Fabiano A, Rizzetto M: Medical management of chronic delta hepatitis.In Viral Hepatitis and Liver Disease. FB Hollinger, SM Lemon, HS Margolis (eds). Baltimore, Williams & Wilkins, 1991, pp 627–629Google Scholar
  111. 111.
    Garcia G, Scullard G, Smith C, Weissberg J, Alexander S, Robinson WS, Gregory P, Merigan TC: Preliminary observation of hepatitis B-associated membranous glomerulonephritis treated with leukocyte interferon. Hepatology 5:317–320, 1985Google Scholar
  112. 112.
    Mizushima N, Kanai K, Matsuda H, Matsumoto M, Tamakoshi K, Ishii H, Nakajima T, Yoshimi T, Kimura M, Nagase M: Improvement of proteinuria in a case of hepatitis B associated glomerulonephritis after treatment with interferon. Gastroenterology 92:524–526, 1987Google Scholar
  113. 113.
    Lisker-Melman M, Webb D, Di Bisceglie AM, Kassianides C, Martin P, Rustgi V, Waggoner JG, Park Y, Hoofnagle JH: Glomerulonephritis caused by chronic hepatitis B virus infection: treatment with recombinant human alpha-interferon. Ann Intern Med 3:479–483, 1989Google Scholar
  114. 114.
    Kassianides C, Di Bisceglie AM, Hoofnagle JH, Mullen K, Peters M, Rustgi V, Jones B, Lisker-Melman M, Park Y, Waggoner JG, Jones EA: Alpha interferon therapy in patients with decompensated chronic type B hepatitis.In Viral Hepatitis and Liver Disease. AJ Zuckerman (ed). New York, Alan R. Liss, 1988, pp 840–843Google Scholar
  115. 115.
    Hoofnagle JH, Di Bisceglie AM, Waggoner JG, Park Y: Alpha interferon treatment of patients with clinically apparent cirrhosis due to chronic hepatitis B. Gastroenterology (in press)Google Scholar
  116. 116.
    Perrillo R, Tamburro C, Regenstein F, Balart L, Bodenheimer H, Schiff E, Silva M, Albrecht J, Bodicky C, Campbell C, Miller B, Taylor B, Brodeur C, Roach K: Treatment of decompensated chronic hepatitis B (CHB) with a titrable, low dose regimen of recombinant interferon alfa-2b. Hepatology 16:126A, 1992Google Scholar

Copyright information

© Plenum Publishing Corporation 1993

Authors and Affiliations

  • Robert P. Perrillo
    • 2
    • 1
  1. 1.Washington University School of MedicineWashingtonUSA
  2. 2.Gastroenterology SectionSt. Louis Veterans Affairs Medical Center (111 JC)Saint Louis

Personalised recommendations