Skip to main content

Advertisement

SpringerLink
Log in

Risks and Benefits of Interferon-α in the Treatment of Hepatitis

  • Review Article
  • Risk-Benefit Assessment
  • Published:
Drug Safety Aims and scope Submit manuscript

Summary

The high worldwide prevalence of chronic viral hepatitis, as well as its progressive course, have led to the performance of multiple clinical studies. The natural history of the disease is different depending on the infecting virus; thus, the evolution to liver cirrhosis and/or hepatocellular carcinoma for the hepatitis B, C and delta (D) viruses in chronic hepatitis is 15, 20 and 75%, respectively. Different therapeutic agents have been used in attempts to modify the natural course of these diseases, interferon-α (IFNα) having proved to be the most effective.

In 30 to 50% of patients, treatment with IFNα has achieved inhibition of viral replication, as well as normalisation of aminotransferase levels. Moreover, in a majority of patients, histological improvement is observed, principally in piecemeal necrosis and portal inflammation. The dosage currently recommended for treatment of chronic hepatitis B is 30 to 35MU weekly for a minimum of 4 months; when there is a co-existing delta virus infection, the total dosage employed should be greater. For hepatitis C, the minimum effective dosage is 9MU weekly, and a treatment duration of 12 months is recommended.

The administration of IFNα produces a series of dose-dependent adverse effects, which are reversible on suspension of the medication. The most frequent of these adverse reactions is the ’flu-like’ syndrome, which is self-limited and generally well tolerated. Secondary haematological alterations (leucopenia and thrombocytopenia) are the most frequent cause of reduction in dosage or suspension of treatment, although the latter is not normally necessary. The proportion of patients requiring dosage modification or suspension of treatment fluctuates between 5 and 15%.

Taking the evolution of chronic hepatitis into account, there can be no doubt that all patients with this disease should be offered treatment. At present, the drug of choice is IFNα, as it slows disease progression and it is generally well tolerated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Cirelli R, Tyring SK. Major therapeutic uses of interferons. Clin Immunother 1995; 3: 27–87

    Google Scholar 

  2. Maynard JE. Hepatitis B: global importance and need for control. Vaccine 1990; 8 Suppl.: S18–20

    PubMed  Google Scholar 

  3. Stevens CE, Toy PT, Tong MJ, et al. Yeast recombinant hepatitis B vaccine: efficacy with hepatitis B immunoglobulin in prevention of perinatal hepatitis B virus transmission. JAMA 1987; 257: 2612–6

    PubMed  CAS  Google Scholar 

  4. Wright TL. Chronic hepatitis B and C: what is the status of drug therapy? Postgrad Med 1992; 92: 75–82

    PubMed  CAS  Google Scholar 

  5. Rizzetto M, Canese MG, Arico S, et al. Immunofluorescence detection of a new antigen-antibody system (d/anti-d) associated to hepatitis B virus in liver and serum of HBsAg carriers. Gut 1977; 18: 997–1003

    PubMed  CAS  Google Scholar 

  6. Ottobrelli A, Marzano A, Smedile A, et al. Patterns of hepatitis delta virus reinfection and disease in liver transplantation. Gastroenterology 1991; 101: 1649–55

    PubMed  CAS  Google Scholar 

  7. Lau JYN, Alexander GJ, Alberti A. Viral hepatitis. Gut 1991; 1 Suppl.: S47–62

    Google Scholar 

  8. Hoofnagle JH. Chronic hepatitis B. N Engl J Med 1990; 323: 337–9

    PubMed  CAS  Google Scholar 

  9. Mattsson L, Weiland O, Glaumann H. Chronic non-A, non-B hepatitis developed after transfusions, illicit self-injections or sporadically: outcome during long-term follow-up — a comparison. Liver 1989; 9: 120–7

    PubMed  CAS  Google Scholar 

  10. Verme G, Brunetto MR, Oliveri F, et al. Role of hepatitis delta virus infection in hepatocellular carcinoma. Dig Dis Sci 1991; 36: 1134–6

    PubMed  CAS  Google Scholar 

  11. Isaacs A, Lindenmann J. Virus interference. I. The interferon. II. Some properties of interferon. Proc R Soc Lond B 1957; 147: 268–73

    PubMed  CAS  Google Scholar 

  12. Díaz M, Bohlander S, Allen G. Nomenclature of human interferon genes. J Interferon Res 1993; 13: 243–4

    PubMed  Google Scholar 

  13. Gresser I. Production of interferon by suspensions of human leucocytes. Proc Soc Exp Biol Med 1961; 108: 799–803

    PubMed  CAS  Google Scholar 

  14. Gray P, Leung D, Pennia D, et al. Expression of human immune interferon cDNA in E. coli and monkey cells. Nature 1982; 295: 503–8

    PubMed  CAS  Google Scholar 

  15. Branca AA, Baglioni C. Evidence that types I and II interferons have different receptors. Nature 1981; 294: 768–70

    PubMed  CAS  Google Scholar 

  16. Weitz G, Bekisz J, Zoon K, et al. Purification and characterization of a human Mx protein. J Interferon Res 1989; 9: 679–89

    PubMed  CAS  Google Scholar 

  17. Pestka S, Lauger JA, Zoon KC, et al. Interferon and their actions. Ann Rev Biochem 1987; 56: 727–77

    PubMed  CAS  Google Scholar 

  18. Horisberger MA, Gunst MC. Interferon-induced proteins: identification of Mx proteins in various mammalian species. Virology 1991; 180(1): 185–90

    PubMed  CAS  Google Scholar 

  19. De Maeyer-Guignard J, De Maeyer E. Immunomodulation by interferons: recent developments. Interferon 1985; 6: 69–91

    PubMed  Google Scholar 

  20. Middleton PG, Prince RA, Williamson IK, et al. Alpha interferon gene deletions in adults, children and infants with acute lymphoblastic leukemia. Leukemia 1991; 5(8): 680–2

    PubMed  CAS  Google Scholar 

  21. Willson JKV, Bittner G, Borden EC. Antiproliferative activity of human interferons against ovarian cancer cells grown in human tumor stem cells assay. J Interferon Res 1984; 4: 441–7

    PubMed  CAS  Google Scholar 

  22. Saiki I, Dunegan MA, Fann AV, et al. Regulatory effects on macrophages of human recombinant interferon alpha. J Interferon Res 1986; 6: 603–11

    PubMed  CAS  Google Scholar 

  23. Streuli M, Nagata S, Weissmann C. At least three human type-alpha interferons: structure of alpha-2. Science 1980; 209: 1343–7

    PubMed  CAS  Google Scholar 

  24. Nakagawa S, Honda S, Jugino H, et al. Characterization of three species of Escherichia coli-derived human leukocyte interferon A separated by reverse-phase high performance liquid chromatography. J Interferon Res 1987; 7: 285–99

    PubMed  CAS  Google Scholar 

  25. Rumi MG, Romeo R, Parravicini ML, et al. Randomized comparative study of recombinant alpha and lymphoblastoid interferon in patients with chronic active hepatitis C. J Hepatol 1994; 18: 527–30

    Google Scholar 

  26. Perrillo RP. Interferon in the management of chronic hepatitis B. Dig Dis Sci 1993; 38: 577–93

    PubMed  CAS  Google Scholar 

  27. Vallbracht A, Treuner T, Flechmig B, et al. Interferon neutralizing antibodies in a patients treated with human fibroblast interferon. Nature 1981; 287: 496–8

    Google Scholar 

  28. Porres JC, Carreno V, Ruiz M, et al. Interferon antibodies in patients with chronic HBV infection treated with recombinant interferon. J Hepatol 1989; 8: 351–7

    PubMed  CAS  Google Scholar 

  29. Antonelli G, Currenti M, Turriziani O, et al. Neutralizing antibodies to interferon-alpha: relative frequency in patients treated with different interferon preparations. J Infect Dis 1991; 163: 882–5

    PubMed  CAS  Google Scholar 

  30. Cimino L, Citarella C, Nardone G, et al. Lymphoblastoid interferon in chronic hepatitis C patients, non-responders to recombinant interferon-alpha (rIFN-alpha). J Hepatol 1992; 14: 419–20

    PubMed  CAS  Google Scholar 

  31. Hoofnagle JH. Interferon therapy of viral hepatitis. In: Baron S, Coppenhaver DH, Dianzani F, et al., editors. Interferon: principles and medical applications. Galveston, TX: The University of Texas Medical Branch at Galveston, Department of Microbiology 1992; 31: 433–62

  32. Hoofnagle JH, Peters M, Mullen KD, et al. Randomized, controlled trial of recombinant human alpha interferon in patients with chronic type B hepatitis. Gastroenterology 1988; 95: 1318–25

    PubMed  CAS  Google Scholar 

  33. Perrillo RP, Schiff ER, Davis GL, et al. Arandomized controlled trial of interferon alpha-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. N Engl J Med 1990; 323: 295–301

    PubMed  CAS  Google Scholar 

  34. Di Bisceglie AM, Bergasa NV, Fong TL, et al. A randomized, controlled trial of recombinant alpha interferon therapy for chronic hepatitis B. Hepatology 1991; 13: 70A

    Google Scholar 

  35. Alexander GJ, Brahm J, Fagan EA, et al. Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection. Lancet 1987; ii: 66–9

    Google Scholar 

  36. Müller R, Baumgarten R, Markus R, et al. Treatment of chronic hepatitis B with interferon alpha-2b. J Hepatol 1990: 11: Suppl. 1: S137–40

    PubMed  Google Scholar 

  37. Pastore G, Santantonio T, Monno L, et al. Permanent inhibition of viral replication induced by low dosage of human leukocyte interferon in patients with chronic hepatitis B. Hepatogastroenterology 1988; 35: 57–61

    PubMed  CAS  Google Scholar 

  38. Carreno V, Porres JC, Mora I, et al. A controlled study of treatment with recombinant interferon alpha in chronic hepatitis B virus infection: induction and maintenance schedules. Antiviral Res 1987; 8: 125–37

    PubMed  CAS  Google Scholar 

  39. Waked I, Amin M, Abd el Fattah S, et al. Experience with interferon in chronic hepatitis B in Egypt. J Chemother 1990; 2: 310–8

    PubMed  CAS  Google Scholar 

  40. Lok AS, Wu PC, Lai CL, et al. A controlled trial of interferon with or without prednisone priming for chronic hepatitis B. Gastroenterology 1992; 102: 2091–7

    PubMed  CAS  Google Scholar 

  41. Brook MG, Petrovic L, McDonald JA, et al. Histological improvement after antiviral treatment for chronic hepatitis B infection. J Hepatol 1989; 8: 218–25

    PubMed  CAS  Google Scholar 

  42. Perrillo RP. Factors influencing response to interferon in chronic hepatitis B: implications for Asian and Western population [editorial]. Hepatology 1990; 12: 1433–5

    PubMed  CAS  Google Scholar 

  43. Davis GL, Hoofnagle JH, Waggoner JG. Spontaneous reactivation of chronic hepatitis B virus infection. Gastroenterology 1984; 86: 230–5

    PubMed  CAS  Google Scholar 

  44. Yoffe B, Burns DK, Bhatt H, et al. Extrahepatic hepatitis B virus DNA sequences in patients with acute hepatitis B infection. Hepatology 1990; 12: 187–92

    PubMed  CAS  Google Scholar 

  45. Kuhns M, McNamara A, Mason A, et al. Serum and liver hepatitis B virus DNA in chronic hepatitis B after sustained loss of surface antigen. Gastroenterology 1992; 103: 1649–56

    PubMed  CAS  Google Scholar 

  46. Michalak TI, Pasquinelli C, Guilhot S, et al. Hepatitis B virus persistence after recovery from acute viral hepatitis. J Clin Invest 1994; 93: 230–9

    PubMed  CAS  Google Scholar 

  47. Liaw YF, Lin DY, Chen TJ, et al. Natural course after the development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Liver 1989; 9: 235–41

    PubMed  CAS  Google Scholar 

  48. McMahon BJ, Alberts SR, Waumwright RB, et al. Hepatitis B-related sequelae. Prospective study in 1400 hepatitis B surface antigen-positive Alaska native carriers. Ann Intern Med 1990; 150: 1051–4

    CAS  Google Scholar 

  49. Werssberg JI, Andres LL, Smith CI, et al. Survival in chronic hepatitis B. An analysis of 379 patients. Ann Intern Med 1984; 101: 613–6

    Google Scholar 

  50. Peters M, Vierling J, Gershwin ME, et al. Immunology and the liver. Hepatology 1991; 13: 977–94

    PubMed  CAS  Google Scholar 

  51. McDonald JA, Caruso L, Karayiannis P, et al. Diminished responsiveness of male homosexual chronic hepatitis B virus carriers with HTLV-III antibodies to recombinant alpha interferon. Hepatology 1987; 7: 719–23

    PubMed  CAS  Google Scholar 

  52. Brooks MG, Karayiannis P, Thomas HC, et al. Which patients with chronic hepatitis B virus infection will respond to alpha interferon therapy? A statistical analysis of predictive factors. Hepatology 1989; 10: 761–3

    Google Scholar 

  53. Hoofnagle JH, Smedile A, Mullen K, et al. Treatment of chronic delta hepatitis with recombinant human alpha-interferon. Gastroenterology 1985; 88: 1665

    Google Scholar 

  54. Porres JC, Carreno V, Bartolomé J, et al. Treatment of chronic hepatitis delta infection with recombinant human interferon alpha-2a at high doses. J Hepatol 1989; 9: 338–44

    PubMed  CAS  Google Scholar 

  55. Farci P, Mandas A, Coiana A, et al. Treatment of chronic hepatitis D with interferon alpha-2a. N Engl J Med 1994; 330: 88–94

    PubMed  CAS  Google Scholar 

  56. Madejón A, Cotonat T, Bartolomé J, et al. Treatment of chronic hepatitis D virus infection with low and high doses of interferon alpha-2a: utility of polymerase chain reaction in monitoring antiviral response. Hepatology 1994; 19: 1331–6

    PubMed  Google Scholar 

  57. Simmonds P, Holmes EC, Cha TA, et al. Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 1993; 74: 2391–9

    PubMed  CAS  Google Scholar 

  58. Takada N, Takase S, Enomoto N, et al. Clinical backgrounds of the patients having different types of hepatitis C virus genomes. J Hepatol 1992; 14: 35–40

    PubMed  CAS  Google Scholar 

  59. Yoshioka K, Kamuku S, Wakita T, et al. Detection of hepatitis C virus by polymerase chain reaction and response to interferon alpha therapy: relationship to genotypes of hepatitis C virus. Hepatology 1992; 16: 293–9

    PubMed  CAS  Google Scholar 

  60. Hoofnagle JH, Mullen KD, Jones DB, et al. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon: a preliminary report. N Engl J Med 1986; 315: 1575–8

    PubMed  CAS  Google Scholar 

  61. Davis GL, Baiart LA, Schiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alpha. A multicenter randomized, controlled trial. N Engl J Med 1989; 321: 1501–6

    PubMed  CAS  Google Scholar 

  62. Di Bisceglie AM, Martin P, Kassianides C, et al. Recombinant interferon alpha: therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. N Engl J Med 1989; 321: 1506–10

    PubMed  Google Scholar 

  63. Jacyna MR, Brooks MG, Loke RHT, et al. Randomised controlled trial of interferon alpha (lymphoblastoid interferon) in chronic non-A, non-B hepatitis. BMJ 1989; 298: 80–2

    PubMed  CAS  Google Scholar 

  64. Goméz-Rubio M, Porres JC, Castillo I, et al. Prolonged treatment (18 months) of chronic hepatitis C with recombinant alpha-interferon in comparison with a control group. J Hepatol 1990; 11: S63–7

    PubMed  Google Scholar 

  65. Sáez-Royuela F, Porres JC, Moreno A, et al. High doses of recombinant alpha-interferon or gamma-interferon for chronic hepatitis C: a randomized controlled trial. Hepatology 1991; 13: 327–31

    PubMed  Google Scholar 

  66. Marcellin P, Boyer N, Giostra E, et al. Recombinant human alpha-interferon in patients with chronic non-A, non-B hepatitis: a multicenter randomized controlled trial from France. Hepatology 1991; 13: 394–7

    Google Scholar 

  67. Diodati G, Bonetti P, Noventa F, et al. Treatment of chronic hepatitis C with recombinant human interferon alpha-2a: results of a randomized controlled clinical trial. Hepatology 1994; 19: 1–5

    PubMed  CAS  Google Scholar 

  68. Negro F, Baldi M, Mondardini A, et al. Continuous versus intermittent therapy for chronic hepatitis C with recombinant interferon alpha-2a. Gastroenterology 1994; 107: 479–85

    PubMed  CAS  Google Scholar 

  69. Reichard O, Foberg U, Frydén A, et al. High sustained response rate and clearance of viremia in chronic hepatitis C after treatment with interferon alpha-2b for 60 weeks. Hepatology 1994; 19: 280–5

    PubMed  CAS  Google Scholar 

  70. Kasahara A, Hayashi N, Hiramatsu N, et al. Ability of prolonged interferon treatment to suppress relapse after cessation of therapy in patients with chronic hepatitis C: a multicenter randomized controlled trial. Hepatology 1995; 21: 291–7

    PubMed  CAS  Google Scholar 

  71. Lindsay KL, Davis GL, Schiff ER, et al. Long-term response to higher doses of interferon alpha-2b treatment of patients with chronic hepatitis C: a randomized multicenter trial. Hepatology 1993; 18: 106A

    Google Scholar 

  72. Finter NB, Chapman S, Dowd P, et al. The use of interferon-alpha in virus infections. Drugs 1991; 42(5): 749–65

    PubMed  CAS  Google Scholar 

  73. Jouët P, Roudot-Thoraral F, Dhumeaux D, et al. Comparative efficacy of interferon alpha in cirrhotic and non-cirrhotic patients with non-A, non-B, C hepatitis. Gastroenterology 1994; 106: 686–90

    PubMed  Google Scholar 

  74. Poynard T, Bedossa P, Chevallier M, et al. A comparison of three interferon alpha-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. N Engl J Med 1995; 332: 1457–62

    PubMed  CAS  Google Scholar 

  75. Omata M, Ito Y, Yokosuka O, et al. Histological changes of the liver by treatment of chronic non A-non B hepatitis with recombinant leukocyte interferon alpha. Comparison with histological changes in chronic hepatitis B. Dig Dis Sci 1989; 34: 330–7

    PubMed  CAS  Google Scholar 

  76. Jeffers LJ, Dailey PJ, Cohelho-Litle E, et al. Correlation of HCV RNA quantification in sera and liver tissue of patients with chronic C hepatitis. Gastroenterology 1993; 104: A923

    Google Scholar 

  77. Mosnier JF, Depott C, Marcellin P, et al. Intraportal lymphoid nodules: a histologic lesion distinctive of chronic hepatitis C. J Hepatol 1991; 13 Suppl. 2: S54

    Google Scholar 

  78. Schoeman MN, Liddle C, Billows M, et al. Chronic non-A, non-B: lack of correlation between biochemical and morphological activity and effects of immunosuppressive therapy on disease progression. Aust NZ J Med 1990; 20: 56–62

    CAS  Google Scholar 

  79. Silini E, Bono F, Cividini A, et al. Differential distribution of hepatitis C virus genotypes in patients with and without liver function abnormalities. Hepatology 1995; 21: 285–90

    PubMed  CAS  Google Scholar 

  80. Yamada G, Takahashi M, Miyamoto R, et al. Prediction of interferon effect in chronic hepatitis C by both quantification and genotyping of HCV-RNA [letter]. Dig Dis Sci 1994; 39: 441–7

    PubMed  CAS  Google Scholar 

  81. Mita E, Hayashi N, Hagiwara H, et al. Predicting interferon therapy efficacy from hepatitis C virus genotype and RNA titer. Dig Dis Sci 1994; 39: 977–82

    PubMed  CAS  Google Scholar 

  82. Castillo I, Bartolomé J, Navas S, et al. Virological and biochemical long-term follow-up of patients with chronic hepatitis C treated with interferon. Hepatology 1994; 19: 1342–6

    PubMed  CAS  Google Scholar 

  83. Balart LA, Perrillo R, Roddenberry J. Hepatitis C RNA in liver of chronic hepatitis C patients before and after interferon alpha treatment. Gastroenterology 1993; 104: 1472–7

    PubMed  CAS  Google Scholar 

  84. Shindo M, Arai K, Sokawa Y, et al. Hepatic hepatitis C virus RNA as a predictor of a long-term response to interferon-alpha therapy. Ann Intern Med 1995; 122: 586–91

    PubMed  CAS  Google Scholar 

  85. Hagiwara H, Hayashi N, Mita E, et al. Quantitative analysis of hepatitis C virus RNA in serum during interferon alpha therapy. Gastroenterology 1993; 104: 877–83

    PubMed  CAS  Google Scholar 

  86. Lau JYN, Davis GL, Kniffen J, et al. Significance of serum hepatitis C virus RNA levels in chronic hepatitis. Lancet 1993; 341: 1501–4

    PubMed  CAS  Google Scholar 

  87. van Doom LJ. Molecular biology of the hepatitis C virus. J Med Virol 1994; 43: 345–56

    Google Scholar 

  88. Davis GL, Lindsay K, Albrecht J, et al. Clinical predictors of response to recombinant alpha interferon treatment in patients with chronic non-A, non-B hepatitis (hepatitis C). J Viral Hepatitis 1994; 1: 55–63

    CAS  Google Scholar 

  89. Mazzella G, Salzetta A, Casanova S, et al. Treatment of chronic sporadic-type non-A, non-B hepatitis with lymphoblastoid interferon: gamma GT levels predictive for response. Dig Dis Sci 1994; 39: 866–70

    PubMed  CAS  Google Scholar 

  90. Olynyk J, Reddy R, Di Bisceglie AM, et al. Hepatic iron concentration as a predictor of response to alpha interferon therapy in chronic hepatitis C. Gastroenterology 1994; 107: 90A

    Google Scholar 

  91. Seeff LB, Buskell-Bales Z, Wright EC, et al. Long-term mortality after transfusion-associated non-A, non-B hepatitis. N Engl J Med 1992; 327: 1906–11

    PubMed  CAS  Google Scholar 

  92. Alter MJ, Margolsi HS, Krawczynski K, et al. The natural history of community-acquired hepatitis C in the United States. N Engl J Med 1992; 327: 1899–905

    PubMed  CAS  Google Scholar 

  93. Alberti A, Chemello L, Bonetti P, et al. Treatment with interferon(s) of community-acquired chronic hepatitis and cirrhosis type C. J Hepatol 1993; 17: (Suppl. 3): S123–6

    PubMed  Google Scholar 

  94. Lunel F, Musset L, Cacoub P, et al. Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Gastroenterology 1994; 106: 1291–300

    PubMed  CAS  Google Scholar 

  95. Johnson RJ, Gretch DR, Yamabe H, et al. Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl J Med 1993; 328: 465–70

    PubMed  CAS  Google Scholar 

  96. Fargion S, Piperno A, Cappellini MD, et al. Hepatitis C virus and porphyria cutanea tarda: evidence of a strong association. Hepatology 1992; 16: 1322–6

    PubMed  CAS  Google Scholar 

  97. Navas S, Bosch O, Castillo I, et al. Porphyria cutanea tarda and hepatitis C and B viruses infection: a retrospective study. Hepatology 1995: 21: 279–84

    PubMed  CAS  Google Scholar 

  98. Misiani R, Bellavita P, Fenili D, et al. Interferon alpha-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 1994; 330: 751–6

    PubMed  CAS  Google Scholar 

  99. Capra F, Casaril M, Gabrielli GB, et al. Alpha-interferon in the treatment of chronic viral hepatitis: effects on fibrogenesis serum markers. J Hepatol 1993; 18: 112–8

    PubMed  CAS  Google Scholar 

  100. Quesada JR, Talpaz M, Rios A, et al. Clinical toxicity of interferons in cancer patients: a review. J Clin Oncol 1986; 4(2): 234–43

    PubMed  CAS  Google Scholar 

  101. Scott G, Secher D, Geuwers D, et al. Toxicity of interferon. BMJ 1981; 282: 1345–8

    PubMed  CAS  Google Scholar 

  102. Renault PR, Hoofnagle JH. Side effects of alpha-interferon. Semin Liv Dis 1989; 9: 273–7

    CAS  Google Scholar 

  103. Renault PR, Hoofnagle JH, Park Y, et al. Psychiatric complications of long-term interferon alpha therapy. Arch Intern Med 1987; 147: 1577–80

    PubMed  CAS  Google Scholar 

  104. Koivisto VA, Pelkonen R, Cantell K. Effects of interferon on glucose tolerance and insulin sensitivity. Diabetes 1989; 38: 641–7

    PubMed  CAS  Google Scholar 

  105. Ruiz-Moreno M, Carreno V, Rua MJ, et al. Increase in triglycerides during alpha-interferon treatment of chronic viral hepatitis. J Hepatol 1992; 16: 384–8

    PubMed  CAS  Google Scholar 

  106. Quesada JR, Gutterman JU. Psoriasis and alpha-interferon. Lancet 1986; i: 1466

    Google Scholar 

  107. Bjerke JR, Livden JK, Degre M, et al. Interferon in suction blister fluid from psoriatic lesions. Br J Dermatol 1983; 108: 295–9

    PubMed  CAS  Google Scholar 

  108. Martino S, Rtanathrathorn V, Karanes C, et al. Reversible arrhythmias observed in patients treated with recombinant alpha-2 interferon. J Cancer Res Clin Oncol 1987; 113: 376–9

    PubMed  CAS  Google Scholar 

  109. Gutterman JU, Fein S, Quesada J, et al. Recombinant leukocyte A interferon: pharmacokinetics, single-dose tolerance, and biologic effects in cancer patients. Ann Intern Med 1982; 96: 549

    PubMed  CAS  Google Scholar 

  110. Quesada JR, Hawkins M, Merigan TC, et al. A collaborative phase I/II study of recombinant DNA-produced leukocyte interferon (cloned A) in metastatic breast cancer, malignant lymphoma and multiple myeloma. Am J Med 1984; 77: 427–32

    PubMed  CAS  Google Scholar 

  111. Ernstoff MS, Kirkwood JM. Changes in the bone marrow of cancer patients treated with recombinant interferon alpha-2. Am J Med 1984; 76: 593–6

    PubMed  CAS  Google Scholar 

  112. Hoofnagle JH. Thrombocytopenia during interferon alpha therapy. JAMA 1991; 266(6): 849

    PubMed  CAS  Google Scholar 

  113. Causse X, Godinot H, Chevallier M, et al. Comparison of 1 or 3 MU of interferon alpha-2b and placebo in patients with chronic non-A, non-B hepatitis. Gastroenterology 1991; 101: 497–502

    PubMed  CAS  Google Scholar 

  114. McDonald EM, Mann AH, Thomas HC. Interferon as mediator of psychiatric morbidity: an investigation in a trial of recombinant alpha-interferon in hepatitis B-carriers. Lancet 1987; 2: 1175–8

    PubMed  CAS  Google Scholar 

  115. Adams F, Quesada JR, Gutterman JU. Neuro-psychiatric manifestations of human leukocyte interferon therapy in patients with cancer. JAMA 1984: 252: 938

    PubMed  CAS  Google Scholar 

  116. Janssen HLA, Brouwer JT, van der Mast RC, et al. Suicide associated with alpha-interferon therapy for chronic viral hepatitis. J Hepatol 1994; 21: 241–3

    PubMed  CAS  Google Scholar 

  117. Conlou KC, Urba WJ, Smith JW, et al. Exacerbation of symptoms of autoimmune disease in patients receiving alpha-interferon therapy. Cancer 1990; 65: 2237–42

    Google Scholar 

  118. Mayet WJ, Hess G, Gerken G, et al. Treatment of chronic type B hepatitis with recombinant alpha-interferon induces auto-antibodies not specific for autoimmune chronic hepatitis. Hepatology 1989; 10: 24–8

    PubMed  CAS  Google Scholar 

  119. Ronnblom LE, Alm GV, Oberg KE. Autoimmunity after alpha interferon therapy for malignant carcinoid tumor. Ann Intern Med 1991; 115: 178–83

    PubMed  CAS  Google Scholar 

  120. Manns MP. Cytoplasmic autoantigens in autoimmune hepatitis. Molecular analysis and clinical relevance. Semin Liv Dis 1991; 11: 205–14

    CAS  Google Scholar 

  121. Michel G, Ritter A, Gerken G, et al. Anti-GOR and hepatitis C virus in autoimmune liver disease. Lancet 1992; 339: 267–9

    PubMed  CAS  Google Scholar 

  122. Ruiz-Moreno M, Rua MJ, Carreno V, et al. Autoimmune chronic hepatitis type 2 manifested during interferon therapy in children. J Hepatol 1991; 12: 265–6

    PubMed  CAS  Google Scholar 

  123. Castillo I, Bartolomé J, Navas S, et al. Hepatitis C virus replication and hepatocellular damage. J Hepatol 1992; 16: S55

    Google Scholar 

  124. Lunel F, Abuaf N, Frangeul L, et al. Liver/kidney microsome antibody type I and hepatitis C virus infection. Hepatology 1992; 16: 630–6

    PubMed  CAS  Google Scholar 

  125. Pesce A, Rosenthal E, Vinti H, et al. Opportunistic infections and CD4 lymphocytopenia with interferon treatment in HIV-1 infected patients. Lancet 1993; 341: 1597

    PubMed  CAS  Google Scholar 

  126. Hoofnagle JH, Di Bisceglie AM, Waggoner JG, et al. Alpha-interferon treatment of patients with clinically apparent cirrhosis due to chronic hepatitis B. Gastroenterology 1993; 104: 1116–21

    PubMed  CAS  Google Scholar 

  127. Makris M, Preston FE, Triger DR, et al. A randomized controlled trial of recombinant interferon alpha in chronic hepatitis C in hemophiliacs. Blood 1991; 78: 1672–7

    PubMed  CAS  Google Scholar 

  128. Taltavull TC, Boliellas C, Sese E, et al. Interferon may be useful in hemodialysis patients with HCV chronic infection who are candidates to kidney transplant. Hepatology 1994; 20: 337A

    Google Scholar 

  129. Marriott E, Navas S, del Romero J, et al. Treatment with recombinant alpha-interferon of chronic hepatitis C in anti-HIV-positive patients. J Med Virol 1993; 40: 107–11

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hepatology Unit, Fundación Jiménez Díe z, Avda. Reyes Católicos 2, 28040, Madrid, Spain

    Margarita Pardo, Eduardo Marriott, María Conceptión Moliner, Juan Antonio Quiroga &  Vicente Carreño

Authors
  1. Margarita Pardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eduardo Marriott
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. María Conceptión Moliner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juan Antonio Quiroga
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vicente Carreño
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pardo, M., Marriott, E., Moliner, M.C. et al. Risks and Benefits of Interferon-α in the Treatment of Hepatitis. Drug-Safety 13, 304–316 (1995). https://doi.org/10.2165/00002018-199513050-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199513050-00004

Keywords

Search

Navigation