Download PDF
Semin Liver Dis 2002; 22(s1): 007-014
DOI: 10.1055/s-2002-35695
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Current State of Interferon Therapy in the Treatment of Chronic Hepatitis B

Michael P. Manns
  • Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Hannover, Germany
Further Information

Publication History

Publication Date:
25 November 2002 (online)

    Permissions and Reprints

ABSTRACT

Interferon alpha (IFN) has been used in the treatment of chronic hepatitis B for approximately 25 years. Predictors of response include high pretreatment serum levels of alanine aminotransferase (ALT), low serum hepatitis B virus (HBV) DNA levels, and infection in adulthood. However, only one third of patients achieve a durable response to a course of IFN therapy. Predictors of nonresponse include normal serum ALT levels, high serum HBV DNA levels, hepatitis B e antigen (HBeAg)-negative infection, childhood infection, and immunosuppression. IFN is contraindicated in patients with decompensated liver disease. In addition, the need for parenteral administration and a significant incidence of difficult-to-tolerate side effects limit the suitability of IFN for long-term therapy. For most patients with chronic hepatitis B, including those infected neonatally and those with HBeAg-negative disease, safe, tolerable, and effective alternatives to IFN are needed.

KEYWORDS

Hepatitis - chronic hepatitis B - interferon - immunomodulators - antiviral agents

REFERENCES

  • 1 Greenberg H B, Pollard R B, Lutwick L I. Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis.  N Engl J Med . 1976;  295 517-522
    PubMedGoogle Scholar
  • 2 Waked I, Amin M, Abd el Fattah S, Osman L M, Sabbour M S. Experience with interferon in chronic hepatitis B in Egypt.  J Chemother . 1990;  2 310-318
    PubMedGoogle Scholar
  • 3 Alexander G JM, Brahm J, Fagan E A. Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection.  Lancet . 1987;  2 66-69
    PubMedGoogle Scholar
  • 4 Di Bisceglie M A, Fong T-L, Fried M W. A randomized, controlled trial of recombinant α-interferon therapy for chronic hepatitis B.  Am J Gastroenterol . 1993;  88 1887-1892
    PubMedGoogle Scholar
  • 5 Fevery J, Elewaut A, Michielsen P. 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 . 1990;  11(Suppl 1) S108-S112
    PubMedGoogle Scholar
  • 6 Hoofnagle J H, Peters M, Mullen K D. Randomized, controlled trial of recombinant human α-interferon in patients with chronic hepatitis B.  Gastroenterology . 1988;  85 1318-1325
    PubMedGoogle Scholar
  • 7 Lok A SF, Lai C-L, Wu P-C, Leung E KY. Long-term follow-up in a randomised controlled trial of recombinant alpha2-interferon in Chinese patients with chronic hepatitis B infection.  Lancet . 1988;  2 298-302
    PubMedGoogle Scholar
  • 8 Lok A SF, Wu P-C, Lai C-L. A controlled trial of interferon with or without prednisone priming for chronic hepatitis B.  Gastroenterology . 1992;  102 2091-2097
    PubMedGoogle Scholar
  • 9 Muller R, Baumgarten R, Markus R. Treatment of chronic hepatitis B with interferon alfa-2b.  J Hepatol . 1990;  11(Suppl 1) S137-S140
    PubMedGoogle Scholar
  • 10 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 . 1990;  11(Suppl 1) S113-S117
    PubMedGoogle Scholar
  • 11 Perrillo R P, Regenstein F G, Peters M G. Prednisone withdrawal followed by recombinant alpha interferon in the treatment of chronic type B hepatitis: a randomized, controlled trial.  Ann Intern Med . 1988;  109 95-100
    PubMedGoogle Scholar
  • 12 Perrillo R P, Schiff E R, Davis G L. A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B.  N Engl J Med . 1990;  323 295-301
    PubMedGoogle Scholar
  • 13 Saracco G, Mazzella G, Rosina F. A controlled trial of human lymphoblastoid interferon in chronic hepatitis B in Italy.  Hepatology . 1989;  10 336-341
    PubMedGoogle Scholar
  • 14 Malik A H, Lee W M. Chronic hepatitis B virus infection: treatment strategies for the next millennium.  Ann Intern Med . 2000;  132 723-731
    PubMedGoogle Scholar
  • 15 Wong D KH, Cheung A M, O'Rourke K. Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B: a meta-analysis.  Ann Intern Med . 1993;  119 312-323
    PubMedGoogle Scholar
  • 16 Williams S J, Craig P I, Cooksley W G. Randomised controlled trial of recombinant human interferon-α A for chronic active hepatitis B.  Aust NZ J Med . 1990;  20 9-19
    PubMedGoogle Scholar
  • 17 Brook M G, McDonald J A, Karayiannis P. Randomised controlled trial of interferon alfa 2A (rbe) (Roferon-A) for the treatment of chronic hepatitis B virus (HBV) infection: factors that influence response.  Gut . 1989;  30 1116-1122
    PubMedGoogle Scholar
  • 18 Brook M G, Chan G, Yap I. Randomised controlled trial of lymphoblastoid interferon alfa in Europid men with chronic hepatitis B virus infection.  BMJ . 1989;  299 652-656
    CrossrefPubMedGoogle Scholar
  • 19 Realdi G, Fattovich G, Pastore G. Problems in the management of chronic hepatitis B with interferon: experience in a randomized multicentre study.  J Hepatol . 1990;  11(Suppl 1) S129-S132
    PubMedGoogle Scholar
  • 20 Porres J C, Carreno V, Mora I. Different doses of recombinant alpha interferon in the treatment of chronic hepatitis B patients without antibodies against the human immunodeficiency virus.  Hepatogastroenterology . 1988;  35 300-303
    PubMedGoogle Scholar
  • 21 Pastore G, Santantonio T, Monno L. Permanent inhibition of viral replication induced by low dosage of human leukocyte interferon in patients with chronic hepatitis B.  Hepatogastroenterology . 1988;  35 57-61
    PubMedGoogle Scholar
  • 22 Carreno V, Porres J C, Mora I. A controlled study of treatment with recombinant interferon alpha in chronic hepatitis B virus infection: induction and maintenance schedules.  Antiviral Res . 1987;  8 125-137
    CrossrefPubMedGoogle Scholar
  • 23 Schiff E R. Treatment algorithms for hepatitis B and C.  Gut . 1993;  34(Suppl 2) S148-S149
    PubMedGoogle Scholar
  • 24 Shaw T, Locarnini S. Combination chemotherapy for hepatitis B virus: the path forward?.  Drugs . 2000;  60 517-531
    PubMedGoogle Scholar
  • 25 Gervais A, Boyer N, Marcellin P. Tolerability of treatments for viral hepatitis.  Drug Safety . 2001;  24 375-384
    PubMedGoogle Scholar
  • 26 Schalm S W, Heathcote J, Cianciara J. Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomised trial.  Gut . 2000;  46 562-568
    CrossrefPubMedGoogle Scholar
  • 27 Niederau C, Heintges T, Lange S. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B.  N Engl J Med . 1996;  334 1422-1427
    CrossrefPubMedGoogle Scholar
  • 28 Lok A SF, McMahon B J. Chronic hepatitis B.  Hepatology . 2001;  34 1225-1241
    CrossrefPubMedGoogle Scholar
  • 29 Lin S M, Sheen I S, Chien R N, Chu C M, Liaw Y F. Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection.  Hepatology . 1999;  29 971-975
    CrossrefPubMedGoogle Scholar
  • 30 Lau D T, Everhart J, Kleiner D E. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa.  Gastroenterology . 1997;  113 1660-1667
    PubMedGoogle Scholar
  • 31 Lok A S, Chung H T, Liu V WS, Ma O CK. Long-term follow-up of chronic hepatitis B patients treated with interferon alpha.  Gastroenterology . 1993;  105 1833-1838
    PubMedGoogle Scholar
  • 32 Korenman J, Baker B, Waggoner J. Long-term remission of chronic hepatitis B after alpha-interferon therapy.  Ann Intern Med . 1991;  114 629-634
    PubMedGoogle Scholar
  • 33 Krogsgaard K. The long-term effect of treatment with interferon-alpha 2a in chronic hepatitis B. The Long-Term Follow-up Investigator Group. The European Study Group on Viral Hepatitis (EURHEP) Executive Team on Anti-Viral Treatment.  J Viral Hepatol . 1998;  5 389-397
    CrossrefPubMedGoogle Scholar
  • 34 Manesis E K, Hadziyannis S J. Interferon α treatment and retreatment of hepatitis B e antigen-negative chronic hepatitis B.  Gastroenterology . 2001;  121 101-109
    CrossrefPubMedGoogle Scholar
  • 35 Brunetto M R, Oliveri F, Colombatto P. Treatment of chronic anti-HBe-positive hepatitis B with interferon-alpha.  J Hepatol . 1995;  22(Suppl 1) 42-44
    PubMedGoogle Scholar
  • 36 Hadziyannis S, Bramou T, Makris A. Interferon alfa-2b treatment of HBeAg negative/serum HBV DNA positive chronic active hepatitis type B.  J Hepatol . 1990;  11(Suppl 1) S133-S136
    PubMedGoogle Scholar
  • 37 Pastore G, Santantonio T, Milella M. Anti-HBe-positive chronic hepatitis B with HBV-DNA in the serum response to a 6-month course of lymphoblastoid interferon.  J Hepatol . 1992;  14 221-225
    PubMedGoogle Scholar
  • 38 Brunetto M R, Oliveri F, Coco B. Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study.  J Hepatol . 2002;  36 263-370
    PubMedGoogle Scholar
  • 39 Lampertico P, Del Ninno E, Manzin A. A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum.  Hepatology . 1997;  26 1621-1625
    PubMedGoogle Scholar
  • 40 Lok A S, Heathcote E J, Hoofnagle J H. Management of hepatitis B: 2000-summary of a workshop.  Gastroenterology . 2001;  120 1828-1853
    PubMedGoogle Scholar
  • 41 Papatheodoridis G V, Manesis E, Hadziyannis S J. The long-term outcome of interferon-α treated and untreated patients with HBeAg-negative chronic hepatitis B.  J Hepatol . 2001;  34 306-313
    CrossrefPubMedGoogle Scholar
  • 42 Yuen M-F, Hui C-K, Cheng C-C. Long-term follow-up of interferon alfa treatment in Chinese patients with chronic hepatitis B infection: the effect on hepatitis B e antigen seroconversion and the development of cirrhosis-related complications.  Hepatology . 2001;  34 139-145
    CrossrefPubMedGoogle Scholar
  • 43 Camma C, Giunta M, Andreone P, Craxi A. Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach.  J Hepatol . 2001;  34 593-602
    CrossrefPubMedGoogle Scholar
  • 44 International Interferon-α/Hepatocellular Carcinoma Study Group. Effect of interferon-α on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study.  Lancet . 1998;  351 1535-1539
    CrossrefPubMedGoogle Scholar
  • 45 Hoofnagle J H, Di Bisceglie M A. The treatment of chronic viral hepatitis.  N Engl J Med . 1997;  336 347-356
    PubMedGoogle Scholar
  • 46 Brook M G, Karayiannis P, Thomas H C. Which patients with chronic hepatitis B virus infection will respond to alpha-interferon therapy?.  <~>A statistical analysis of predictive factors. Hepatology . 1989;  10 761-763
    PubMedGoogle Scholar
  • 47 Manns M P, Rambusch E G. Autoimmunity and extrahepatic manifestations in hepatitis C.  J Hepatol . 1999;  31(Suppl 1) 39-42
    PubMedGoogle Scholar
  • 48 Manns M P. Syllabus. AASLD Single Topic Conference; April, 2002; Chicago, Illinois
    Google Scholar

1 *These studies used various assays for HBV DNA, and in some instances the LLQ was not specified. At the time the studies were conducted, however, more precise quantitative assays were not commonly used

      >