Digestive Diseases and Sciences

, Volume 56, Issue 1, pp 208–212 | Cite as

Long-Term Effect of Interferon Therapy in Patients with HBeAg Positive Chronic Hepatitis B Infection

  • Hakan SenturkEmail author
  • Birol Baysal
  • Veysel Tahan
  • Hasan Zerdali
  • Resat Ozaras
  • Fehmi Tabak
  • Ali Mert
  • Billur Canbakan
  • Omur Tabak
  • Gulsen Ozbay
Original Article



Several studies have reported that interferon therapy increases elimination rate of HBeAg and anti-HBe seroconversion in chronic hepatitis B (CHB) patients. We aimed to evaluate long-term results of interferon-α treatment in HBeAg positive CHB patients in a country with exclusively D genotype.


Seventy-one naive CHB patients (M/F 61/10, mean age 29 ± 12 years, range 16–62) treated with 6 months of interferon-α 2b, 10 MU tiw and had a consequent untreated follow-up period of at least 10 years with positive response were identified and their data were reviewed. The therapy response was defined as HBeAg seroconversion with undetectable HBV-DNA. The responders were followed-up at 3–6-month intervals.


Twenty-eight (39%) patients achieved HBeAg seroconversion (25 within the therapy, 3 within the consequent 12 months off-treatment follow-up). The responders were followed-up with a mean period of 152 months (range 123–181). In the follow-up period, 21/25 (84%) initial responders relapsed. On the other hand, 3 patients who did not respond at the end of therapy sustained the response during follow-up. Hence 21/28 total responders relapsed (75%), either with HBeAg reversion (3, 14.3%) or HBV-DNA elevation over 2000 IU/ml (or its equivalent in other types of definitions) and ALT elevation (18, 85.7%). The sustained response was present in 7 patients (9.8%). Serious side effects precluding completion of treatment occurred in three patients (4.2%). In multivariate analysis none of the pre-treatment parameters appeared to be significant in predicting response.


Sustained response to interferon treatment is low in HBeAg positive CHB patients with genotype D.


Chronic hepatitis B Interferon HBeAg Therapy Genotype Sustained response 



The authors would like to thank Kenneth Dorko from the University of Pittsburgh for his suggestions and critical review of the manuscript.


  1. 1.
    van Zonneveld M, Honkoop P, Hansen BE, et al. Long-term follow-up of alfa-interferon treatment of patients with chronic hepatitis B. Hepatology. 2004;39:804–810.CrossRefPubMedGoogle Scholar
  2. 2.
    Niederau C, Heintges T, Lange S, et al. 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
  3. 3.
    Fattovich G, Giustina G, Realdi G, Corrocher R, Schalm SW. Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa. European Concerted Action on Viral Hepatitis (EUROHEP). Hepatology. 1997;26:1338–1342.CrossRefPubMedGoogle Scholar
  4. 4.
    Buster EH, Flink HJ, Cakaloglu Y, et al. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alfa-2b. Gastroenterology. 2008;135:459–467.CrossRefPubMedGoogle Scholar
  5. 5.
    Lau DTY, Everhart J, Kleiner DE, et al. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa. Gastroenterology. 1997;113:1660–1667.CrossRefPubMedGoogle Scholar
  6. 6.
    Buster EH, Hansen BE, Buti M, et al. Peginterferon alfa-2b is safe and effective in HBeAg-positive chronic hepatitis B patients with advanced fibrosis. Hepatology. 2007;46:388–394.CrossRefPubMedGoogle Scholar
  7. 7.
    Sunbul M, Leblebicioglu H. Distribution of hepatitis B virus genotypes in patients with chronic hepatitis B in Turkey. World J Gastroenterol. 2005;11:1976–1980.PubMedGoogle Scholar
  8. 8.
    Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology. 1981;1:431–435.CrossRefPubMedGoogle Scholar
  9. 9.
    Mazzella G, Saracco G, Festi D, et al. Long-term results with interferon therapy in chronic type B hepatitis: a prospective randomized trial. Am J Gastroenterol. 1999;94:2246–2250.CrossRefPubMedGoogle Scholar
  10. 10.
    Korenman J, Baker B, Waggoner J, Everhart JE, Di Bisceglie AM, Hoofnagle JH. Long-term remission of chronic hepatitis B after alfa-interferon therapy. Ann Intern Med. 1991;114:629–634.PubMedGoogle Scholar
  11. 11.
    Ter Borg MJ, Hansen BE, Bigot G, Haagmans BL, Janssen HLA. ALT and viral load decline during PEG-IFN alfa-2b treatment for HBeAg-positive chronic hepatitis B. J Clin Virol. 2008;42:160–164.CrossRefPubMedGoogle Scholar
  12. 12.
    Fung J, Lai CL, Tanaka Y, et al. The duration of lamivudine therapy for chronic hepatitis B: cessation vs. continuation of treatment after HBeAg seroconversion. Am J Gastroenterol. 2009;104:1940–1946.CrossRefPubMedGoogle Scholar
  13. 13.
    Wu IC, Shiffman ML, Tong MJ, et al. Sustained hepatitis B e antigen seroconversion in patients with chronic hepatitis B after adefovir dipivoxil treatment: analysis of precore and basal core promoter mutants. Clin Infect Dis. 2008;47:1305–1311.CrossRefPubMedGoogle Scholar
  14. 14.
    Hsu YS, Chien RN, Yeh CT, et al. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology. 2002;35:1522–1527.CrossRefPubMedGoogle Scholar
  15. 15.
    Feld JJ, Heathcote EJ. Hepatitis B e antigen-positive chronic hepatitis B: natural history and treatment. Semin Liver Dis. 2006;26:116–129.CrossRefPubMedGoogle Scholar
  16. 16.
    European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol. 2009;50:227–242.CrossRefGoogle Scholar
  17. 17.
    Zhao H, Kurbanov F, Wan MB, et al. Genotype B and younger patient age associated with better response to low-dose therapy: a trial with pegylated/nonpegylated interferon-alpha-2b for hepatitis B e antigen-positive patients with chronic hepatitis B in China. Clin Infect Dis. 2007;44:541–548.CrossRefPubMedGoogle Scholar
  18. 18.
    Yuen MF, Hui CK, Cheng CC, Wu CH, Lai YP, Lai CL. 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
  19. 19.
    Flink HJ, van Zonneveld M, Hansen BE, et al. Treatment with peg-interferon alpha-2b for HBeAg-positive chronic hepatitis B: HBsAg loss is associated with HBV genotype. Am J Gastroenterol. 2006;101:297–303.CrossRefPubMedGoogle Scholar
  20. 20.
    Buster EH, Hansen BE, Lau GK, et al. Factors that predict response of patients with hepatitis B e antigen-positive chronic hepatitis B to peginterferon-alfa. Gastroenterology. 2009;137:2002–2009.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Hakan Senturk
    • 1
    Email author
  • Birol Baysal
    • 1
  • Veysel Tahan
    • 2
  • Hasan Zerdali
    • 1
  • Resat Ozaras
    • 3
  • Fehmi Tabak
    • 3
  • Ali Mert
    • 3
  • Billur Canbakan
    • 1
  • Omur Tabak
    • 4
  • Gulsen Ozbay
    • 5
  1. 1.Cerrahpasa Medical Faculty, Department of GastroenterologyIstanbul UniversityCerrahpasa, IstanbulTurkey
  2. 2.Department of Human ResearchesUniversity of Pittsburgh Medical CenterPittsburghUSA
  3. 3.Cerrahpasa Medical Faculty, Department of Infectious DiseasesIstanbul UniversityIstanbulTurkey
  4. 4.Department of Internal MedicineIstanbul Education and Training HospitalIstanbulTurkey
  5. 5.Cerrahpasa Medical Faculty, Department of PathologyIstanbul UniversityIstanbulTurkey

Personalised recommendations