Skip to main content

Advertisement

Log in

A Practical Guide to the Use of Interferons in the Management of Hepatitis Virus Infections

  • Disease Management
  • Published:
Drugs Aims and scope Submit manuscript

Summary

The recommended interferon dosage for patients with chronic hepatitis and typical hepatitis B virus (HBV) infection is 10MU 3 times weekly for 4 to 6 months; with such a regimen sustained alanine aminotransferase (ALT) normalisation, liver histology improvement, clearance of HBV DNA and serocon version from hepatitis B e antigen (HBeAg) to anti-HBe are obtained in about 40% of treated patients. Patients with elevated disease activity (high ALT values, active chronic hepatitis, low HBV DNA levels) tend to respond better to therapy; Oriental patients and immunocompromised patients are not ideal candidates for interferon. Patients with chronic hepatitis B and the HBeAg-negative variant should be given intermediate dosages (6 to 9MU thrice weekly) of interferon for prolonged periods (12 months); however, even with this approach, the relapse rate is high (>60%) during the follow-up.

In chronic hepatitis D virus (HDV) infection, therapy with 9 to 10MU of interferon 3 times weekly for 12 months induces a transient remission in disease (ALT normalisation, HDV RNA clearance) in more than 50% of treated patients, but a sustained response is found in less than 20% of patients. In such disease, baseline predictive factors of long term response are still unknown.

In chronic hepatitis C, treatment with 3 to 5MU of interferon given 3 times weekly for 6 to 12 months induces a sustained remission in no more than 30% of treated patients. Probable predictive factors of long term response are: low viraemia, genotype other than 1, absence of cirrhosis, low intrahepatic iron content, low nucleotide diversity of the envelope 2 gene of the hepatitis C virus. Prolonged (>12 months) therapeutic courses seem to enhance the sustained response rate; in nonresponders/relapsers, combined therapy (interferon plus indomethacin, interferon plus ketoprofen, interferon plus ribavirin) is promising but randomised controlled trials are needed in order to establish the real efficacy and safety of such therapeutic regimens.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Berris B, Feinman V. Thyroid dysfunction and liver injury following alpha-interferon treatment of chronic viral hepatitis. Dig Dis Sci 1991; 36: 1657–60

    Article  PubMed  CAS  Google Scholar 

  2. Lisker-Melman M, Di Bisceglie AM, Usala SJ, et al. Development of thyroid disease during therapy of chronic viral hepatitis with interferon alfa. Gastroenterology 1992; 102: 2155–60

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  4. McDonald EM, Mann AH, Thomas HC. Interferons as mediators of psychiatric morbidity: an investigation in a trial of recombinant alfa-interferon in hepatitis B carriers. Lancet 1987; II: 1175–8

    Article  Google Scholar 

  5. Papo T, Marcellin P, Bernuau J, et al. Autoimmune chronic hepatitis exacerbated by alpha-interferon. Ann Intern Med 1992; 116: 51–3

    PubMed  CAS  Google Scholar 

  6. Garcia-Buey L, Garcia-Monzon C, Rodriguez S, et al. Latent autoimmune hepatitis triggered during interferon therapy in patients with chronic hepatitis C. Gastroenterology 1995; 108: 1770–7

    Article  PubMed  CAS  Google Scholar 

  7. Fattovich G, Giustina G, Favarato S, et al. A survey of adverse events in 11241 patients with chronic viral hepatitis treated with alfa interferon. J Hepatol 1996; 24: 38–47

    Article  PubMed  CAS  Google Scholar 

  8. Renault PF, Hoofnagle JH. Side effects of alpha interferon. Semin Liver Dis 1989; 9: 273–6

    Article  PubMed  CAS  Google Scholar 

  9. Roffi L, Colloredo Mels G, Antonelli G, et al. Breakthrough during recombinant interferon alfa therapy in patients with chronic hepatitis C virus infection: prevalence, etiology and management. Hepatology 1995; 21: 645–9

    Article  PubMed  CAS  Google Scholar 

  10. Barbera C, Bortolotti F, Crivellaro C, et al. Recombinant interferon alfa-2a hastens the rate of HBeAg clearance in children with chronic hepatitis B. Hepatology 1994; 20: 287–90

    Article  PubMed  CAS  Google Scholar 

  11. Bortolotti F, Giacchino R, Vajro P, et al. Recombinant interferon-alfa therapy in children with chronic hepatitis C. Hepatology 1995; 22: 1623–7

    Article  PubMed  CAS  Google Scholar 

  12. Gregorio GV, Jara P, Hierro L, et al. Lymphoblastoid interferon alfa with or with out steroid pretreatment in children with chronic hepatitis B: a multicenter controlled trial. Hepatology 1996; 23: 700–7

    Article  PubMed  CAS  Google Scholar 

  13. Mayet WJ, Hess G, Gerken G, et al. Treatment of chronic typeB hepatitis with recombinant alpha-interferon induces autoantibodies not specific for autoimmune chronic hepatitis. Hepatology 1989; 10: 24–8

    Article  PubMed  CAS  Google Scholar 

  14. Saracco G, Touscoz A, Durazzo M, et al. Autoantibodies and response to alpha-interferon in patients with chronic viral hepatitis. J Hepatol 1990; 11: 339–43

    Article  PubMed  CAS  Google Scholar 

  15. Muratori L, Lenzi M, Cataleta M, et al. Interferon therapy in liver/kidney microsomal antibody type 1-positive patients with chronic hepatitis C. J Hepatol 1994; 21: 199–203

    Article  PubMed  CAS  Google Scholar 

  16. Todros L, Saracco G, Durazzo M, et al. Efficacy and safety of interferon alfa therapy in chronic hepatitis C with autoantibodies to liver-kidney microsomes. Hepatology 1995; 22: 1374–8

    Article  PubMed  CAS  Google Scholar 

  17. Brunetto MR, Giarin MM, Oliveri F, et al. Wild type and e antigen-minus hepatitis B viruses and course of chronic hepatitis. Proc Natl Acad Sci USA 1991; 88: 4186–90

    Article  PubMed  CAS  Google Scholar 

  18. Perrillo RP, Brunt EM. Hepatic histologic and immunohisto-chemical changes in chronic hepatitis B after prolonged clearance of hepatitis B e antigen and hepatitis B surface antigen. Ann Intern Med 1991; 115: 113–5

    PubMed  CAS  Google Scholar 

  19. Korenman J, Baker B, Waggoner J, et al. Long-term remission of chronic hepatitis B after alpha-interferon therapy. Ann Intern Med 1991; 114: 629–34

    PubMed  CAS  Google Scholar 

  20. Lok AS, Chung HT, Ma OC. Long-term follow-up of chronic hepatitis B patients treated with interferon alfa. Gastroenterology 1993; 105: 1833–8

    PubMed  CAS  Google Scholar 

  21. Hoofnagle JH, Peters MG, Mullen KD, et al. Randomized controlled trial of a four-month course of recombinant human alpha interferon in chronic type B hepatitis. Gastroenterology 1988; 95: 1318–25

    PubMed  CAS  Google Scholar 

  22. Brook MG, Chan G, Yap I, et al. Randomised controlled trial of lymphoblastoid interferon alfa in Europid men with chronic hepatitis B virus infection. BMJ 1989; 299: 652–6

    Article  PubMed  CAS  Google Scholar 

  23. Saracco G, Mazzella G, Rosina F, et al. A controlled trial of human lymphoblastoid interferon in chronic hepatitis B in Italy. Hepatology 1989; 10: 336–41

    Article  PubMed  CAS  Google Scholar 

  24. Perrillo RP, Schiff ER, Davis GL, et al. A randomised controlled trial of interferon-alfa-2b alone and after prednisone with drawal for the treatment of chronic hepatitis B. N Engl J Med 1990; 323: 295–301

    Article  PubMed  CAS  Google Scholar 

  25. Lok AS, Wu PC, Lai CL, et al. A controlled trial of interferon with or with out prednisone priming for chronic hepatitis B. Gastroenterology 1992; 102: 2091–7

    PubMed  CAS  Google Scholar 

  26. Wong DK, Yim C, Naylor CD, et al. Interferon alfa treatment of chronic hepatitis B: randomized trial in a predominantly homosexual male population. Gastroenterology 1995; 108: 165–71

    Article  PubMed  CAS  Google Scholar 

  27. Cohard M, Poynard T, Mathurin P, et al. Prednisone-interferon combination in the treatment of chronic hepatitis B: direct and indirect metanalysis. Hepatology 1994; 20: 1390–8

    Article  PubMed  CAS  Google Scholar 

  28. Wong JB, Koff RS, Tiné F, et al. Does interferon therapy for chronic hepatitis B reduce the risks of developing cirrhosis and hepatocellular carcinoma?. Ann Intern Med 1995; 122: 664–75

    PubMed  CAS  Google Scholar 

  29. Brunetto MR, Oliveri F, Rocca G, et al. Natural course and response to interferon of chronic hepatitis B accompanied by antibody to hepatitis B e antigen. Hepatology 1989; 10: 198–202

    Article  PubMed  CAS  Google Scholar 

  30. Hadzyiannis SJ, Bramou T, Makris A, et al. Interferon alfa-2b treatment of HBeAg negative/serum HBV-DNA positive chronic active hepatitis type B. J Hepatol 1990; 11 Suppl. 1: 133–6

    Article  Google Scholar 

  31. Pastore G, Santantonio T, Milella M, et al. Anti-HBe-positive chronic hepatitis B with HBV-DNA in the serum response to a 6-month course of lymphoblastoid interferon. J Hepatol 1992; 14: 221–5

    Article  PubMed  CAS  Google Scholar 

  32. Fattovich G, Farci P, Rugge M, et al. A randomized controlled trial of lymphoblastoid interferon-alfa in patients with chronic hepatitis B lacking HBeAg. Hepatology 1992; 15: 584–9

    Article  PubMed  CAS  Google Scholar 

  33. Hadziyannis SJ, Papaioannou C, Savvas S, et al. Long-term alpha-interferon therapy in anti-HBe positive chronic hepatitis B increases significantly the frequency of sustained response [abstract]. Hepatology 1994; 19: 701

    Article  Google Scholar 

  34. Rosina F, Rizzetto M. Treatment of chronic type D (delta) hepatitis with alpha interferon. Semin Liver Dis 1989; 9: 264–6

    Article  PubMed  CAS  Google Scholar 

  35. Rosina F, Pintus C, Meschievitz C, et al. A randomized controlled trial of a 12-month course of recombinant human interferon-alpha in chronic delta (type D) hepatitis: a multicenter Italian study. Hepatology 1991; 13: 1052–6

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  37. Gaudin JL, Faure P, Codinot H, et al. The French experience of treatment of chronic type D hepatitis with a 12 month course of IFN alpha-2b: results of a randomized, controlled trial. Liver 1995; 15: 45–52

    PubMed  CAS  Google Scholar 

  38. Bukh J, Miller RH, Purcell RH. Genetic heterogeneity of Hepatitis C Virus: quasispecies and genotypes. Semin Liv Dis 1995; 15: 41–63

    Article  CAS  Google Scholar 

  39. Okamoto H, Kurai K, Okada SI, et al. Full-length sequence of a hepatitis C virus genome having poor homology to reported isolates: comparative study of four distinct genotypes. Virology 1992; 188: 331–41

    Article  PubMed  CAS  Google Scholar 

  40. Chan SW, McOmish F, Holmes EC, et al. Analysis of a new hepatitis C virus type and its phylogenetic relationship to existing variants. J Gen Virol 1992; 73: 1131–41

    Article  PubMed  CAS  Google Scholar 

  41. Tsubota A, Chayama K, Ikeda K, et al. Factors predictive of response to interferon-alfa therapy in hepatitis C virus infection. Hepatology 1994; 19: 1088–94

    Article  PubMed  CAS  Google Scholar 

  42. 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

    Article  PubMed  CAS  Google Scholar 

  43. Hino K, Sainokami S, Shimoda K, et al. Genotypes and titers of hepatitis C virus for predicting response to interferon in patients with chronic hepatitis C. J Med Virol 1994; 42: 299–305

    Article  PubMed  CAS  Google Scholar 

  44. Martinot-Peignoux M, Marcellin P, Pouteau M, et al. Pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype are the main and independent prognostic factors of sustained response to interferon alfa therapy in chronic hepatitis C. Hepatology 1995; 22: 1050–6

    Article  PubMed  CAS  Google Scholar 

  45. Garson JA, Brillanti S, Whitby K, et al. Analysis of clinical and virological factors associated with response to alpha interferon therapy in chronic hepatitis C. J Med Virol 1995; 45: 348–53

    Article  PubMed  CAS  Google Scholar 

  46. Brillanti S, Foli M, Gaiani S, et al. Persistent hepatitis C virae-mia without liver disease. Lancet 1993; 341: 464–5

    Article  PubMed  CAS  Google Scholar 

  47. Prieto M, Olaso V, Verdú C, et al. Does the healthy hepatitis C virus carrier state really exist? An analysis using polymerase chain reaction. Hepatology 1995; 22: 413–7

    PubMed  CAS  Google Scholar 

  48. Alberti A, Morsica G, Chemello L, et al. Hepatitis C viraemia and liver disease in symptom-free individuals with anti-HCV. Lancet 1992; 340: 697–8

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  51. Saracco G, Rosina F, Torrani Cerenzia MR, et al. A randomized controlled trial of interferon alfa-2b as therapy for chronic nonAnonB hepatitis. J Hepatol 1990; 11: S43–9

    Article  PubMed  Google Scholar 

  52. Weiland O, Schvarcz R, Wejstal R, et al. Therapy of chronic post-transfusion nonAnonB hepatitis with interferon alfa-2b: Swedish experience. J Hepatol 1990; 11 Suppl. 1: S57–62

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  54. Marcellin P, Boyer N, Giostra E, et al. Recombinant human alfa-interferon in patients with chronic non-A, non-B hepatitis: a multicenter randomized controlled trial from France. Hepatology 1991; 13: 393–7

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  56. Causse X, Godinot H, Chevalier M, et al. Comparison of 1 or 3 MU of interferon-alfa-2b and placebo in patients with chronic nonA, nonB hepatitis. Gastroenterology 1991; 101: 497–502

    PubMed  CAS  Google Scholar 

  57. Diodati G, Bonetti P, Noventa F, et al. Treatment of chronic hepatitis C with recombinant human interferon-alfa2a: results of a randomized controlled clinical trial. Hepatology 1994; 19: 1–5

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  59. Chemello L, Bonetti P, Cavalletto L, et al. Randomized trial comparing three different regimens of alpha-2a interferon in chronic hepatitis C. Hepatology 1995; 22: 700–6

    PubMed  CAS  Google Scholar 

  60. Reichard O, Foberg U, Fryden A, et al. High sustained response rate and clearance of viremia in chronic hepatitis C after treatment with interferon-alfa2b for 60 weeks. Hepatology 1994; 19: 280–5

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  62. Yokosuka O, Kato N, Ito Y, et al. Efficacy of long-term interferon treatment in chronic liver disease evaluated by sensitive polymerase chain reaction assay for hepatitis C virus RNA. Gut 1995; 37: 721–6

    Article  PubMed  CAS  Google Scholar 

  63. 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

    Article  PubMed  CAS  Google Scholar 

  64. Lin R, Roach E, Zimmerman M, et al. Interferon alfa-2b for chronic hepatitis C: effects of dose increment and duration of treatment on response rates. Results of the first multicentre Australian trial. J Hepatol 1995; 23: 487–96

    Article  PubMed  CAS  Google Scholar 

  65. Saracco G, Rosina F, Abate ML, et al. Long-term follow-up of patients with chronic hepatitis C treated with different doses of interferon-alfa2b. Hepatology 1993; 18: 1300–5

    Article  PubMed  CAS  Google Scholar 

  66. Zaaijer HL, Cuypers HTM, Reesink HW, et al. Reliability of polymerase chain reaction for detection of hepatitis C virus. Lancet 1993; 341: 722–4

    Article  PubMed  CAS  Google Scholar 

  67. Fried MW, Hoofnagle JH. Therapy of hepatitis C. Semin Liver Dis 1995; 15: 82–91

    Article  PubMed  CAS  Google Scholar 

  68. Saracco G, Rosina F, Abate ML, et al. Long-term response to interferon-alfa2b retreatment in chronic hepatitis C [letter]. J Hepatol 1994; 21: 278–9

    Article  PubMed  CAS  Google Scholar 

  69. Marcellin P, Pouteau M, Boyer N, et al. Retreatment with recombinant interferon-alpha in patients with chronic hepatitis C. J Infect Dis 1993; 167: 780–1

    Article  PubMed  CAS  Google Scholar 

  70. Kakumu S, Yoshioka K. Retreatment with interferon in patients with chronic hepatitis C [letter]. J Hepatol 1994; 21: 483

    Article  PubMed  CAS  Google Scholar 

  71. Andreone P, Cursaro C, Gramenzi A, et al. Alfa-interferon plus indomethacin combined therapy for non-responder patients with chronic hepatitis C [abstract]. Hepatology 1993; 18: 659

    Google Scholar 

  72. Andreone P, Cursaro C, Gramenzi A, et al. Pilot study of alfa-interferon and ketoprofen combined therapy in non-responder patients with chronic hepatitis C: an interim report [abstract]. Gastroenterology 1994; 106: 859

    Google Scholar 

  73. Brillanti S, Garson J, Foli M, et al. A pilot study of combination therapy with ribavirin plus interferon alfa for interferon alfa-resistant chronic hepatitis C. Gastroenterology 1994; 107: 812–7

    Article  PubMed  CAS  Google Scholar 

  74. Schvarcz R, Yun ZB, Sonnerborg A, Weiland O. Combined treatment with interferon alpha-2b and ribavirin for chronic hepatitis C in patients with a previous non-response or nonsustained response to interferon alone. J Med Virol 1995; 46: 43–7

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saracco, G., Rizzetto, M. A Practical Guide to the Use of Interferons in the Management of Hepatitis Virus Infections. Drugs 53, 74–85 (1997). https://doi.org/10.2165/00003495-199753010-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199753010-00005

Keywords

Navigation