Skip to main content
Top
Published in: Journal of Gastroenterology 7/2012

01-07-2012 | Original Article—Liver, Pancreas, and Biliary Tract

Long-term efficacy of interferon therapy in patients with chronic hepatitis B virus infection in Japan

Authors: Fumitaka Suzuki, Yasuji Arase, Yoshiyuki Suzuki, Norio Akuta, Hitomi Sezaki, Yuya Seko, Yusuke Kawamura, Tetsuya Hosaka, Masahiro Kobayashi, Satoshi Saito, Kenji Ikeda, Mariko Kobayashi, Hiromitsu Kumada

Published in: Journal of Gastroenterology | Issue 7/2012

Login to get access

Abstract

Background

Few studies have investigated the long-term effects of interferon (IFN) therapy for chronic hepatitis B (CHB). In this retrospective study, we investigated the efficacy of and predictors of response to IFN therapy in CHB patients.

Methods

We analyzed data for 615 Japanese CHB patients (hepatitis B e antigen [HBeAg]-positive 414, HBeAg-negative 201) treated with IFN, and conducted follow up for a median duration of 8.1 years (range 0.5–23.2). Responders were defined as patients who showed continuously normalized alanine transaminase (ALT) levels, HBeAg clearance, and low hepatitis B virus (HBV) DNA levels at 6 months post-treatment or for a span of more than 6 months until each test point at 1, 3, 5, and 10 years.

Results

The IFN response rates of all patients were 21, 18, 21, 23, and 25% at 6 months and 1, 3, 5, and 10 years, respectively. On multivariate analysis, significant determinants of the outcome of IFN therapy were as follows: at 6 months and 1 year, young age, low HBV DNA levels, and long duration of treatment; at 3 years, long duration of treatment, young age, and high level of albumin; at 5 years, high level of albumin, female, and pretreated with IFN; and at 10 years, HBeAg-negative. Sixty-nine of the 615 patients (11%) achieved seroclearance of hepatitis B surface antigen (HBsAg). On multivariate analysis, age ≥30 years, HBV genotype A, and male were all independent factors predicting the achievement of HBsAg seroclearance.

Conclusion

HBeAg, HBV DNA level, age, sex, albumin, duration of treatment, pretreatment with IFN, and HBV genotype were important factors in determining long-term response to IFN therapy.
Literature
1.
go back to reference Beasley RP, Hwang LW, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22,707 men in Taiwan. Lancet. 1981;2:1129–233.PubMedCrossRef Beasley RP, Hwang LW, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22,707 men in Taiwan. Lancet. 1981;2:1129–233.PubMedCrossRef
2.
go back to reference Dienstag JL, Perrillo RP, Schiff ER, Bartholomew M, Vicary C, Rubin M. A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med. 1995;333:1657–61.PubMedCrossRef Dienstag JL, Perrillo RP, Schiff ER, Bartholomew M, Vicary C, Rubin M. A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med. 1995;333:1657–61.PubMedCrossRef
3.
go back to reference Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003;348:808–16.PubMedCrossRef Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003;348:808–16.PubMedCrossRef
4.
go back to reference Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354:1001–10.PubMedCrossRef Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354:1001–10.PubMedCrossRef
5.
go back to reference Lok ASF, Heathcote EJ, Hoofnagel JH. Management of hepatitis B: 2000–summary of a workshop. Gastroenterology. 2001;120:1828–53.PubMedCrossRef Lok ASF, Heathcote EJ, Hoofnagel JH. Management of hepatitis B: 2000–summary of a workshop. Gastroenterology. 2001;120:1828–53.PubMedCrossRef
6.
go back to reference Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521–31.PubMedCrossRef Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521–31.PubMedCrossRef
7.
go back to reference van Zonneveld M, Honkoop P, Hansen BE, Niesters HG, Darwish Murad S, de Man RA, et al. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology. 2004;39:804–10.PubMedCrossRef van Zonneveld M, Honkoop P, Hansen BE, Niesters HG, Darwish Murad S, de Man RA, et al. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology. 2004;39:804–10.PubMedCrossRef
8.
go back to reference Wong DHK, Cheung AM, O’Rourke K, Naylor CD, Detsky AS, Heathcote J. Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. Ann Intern Med. 1993;119:312–23.PubMed Wong DHK, Cheung AM, O’Rourke K, Naylor CD, Detsky AS, Heathcote J. Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. Ann Intern Med. 1993;119:312–23.PubMed
9.
go back to reference Brook MG, Karayiannis P, Thomas HC. Which patients with chronic hepatitis B virus infection will respond to alpha-interferon therapy? Hepatology. 1989;10:761–3.PubMedCrossRef Brook MG, Karayiannis P, Thomas HC. Which patients with chronic hepatitis B virus infection will respond to alpha-interferon therapy? Hepatology. 1989;10:761–3.PubMedCrossRef
10.
go back to reference Perrillo RP, Schiff ER, Davis GL, Bodenheimer HC Jr, Lindsay K, Payne J, et al. A randomized, controlled trial of interferon alfa-2b alone and after prednisolone withdrawal for the treatment of chronic hepatitis B. N Engl J Med. 1990;323:295–301.PubMedCrossRef Perrillo RP, Schiff ER, Davis GL, Bodenheimer HC Jr, Lindsay K, Payne J, et al. A randomized, controlled trial of interferon alfa-2b alone and after prednisolone withdrawal for the treatment of chronic hepatitis B. N Engl J Med. 1990;323:295–301.PubMedCrossRef
11.
go back to reference Perrillo RP, Lai CL, Liaw YF, Dienstag JL, Schiff ER, Schalm SW, et al. Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B. Hepatology. 2002;36:186–94.PubMedCrossRef Perrillo RP, Lai CL, Liaw YF, Dienstag JL, Schiff ER, Schalm SW, et al. Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B. Hepatology. 2002;36:186–94.PubMedCrossRef
12.
go back to reference Yang YF, Zhao W, Xia HM, Zhong YD, Huang P, Wen J. Long-term efficacy of interferon alpha therapy on hepatitis B viral replication in patients with chronic hepatitis B: a meta-analysis. Antiviral Res. 2010;85:361–5.PubMedCrossRef Yang YF, Zhao W, Xia HM, Zhong YD, Huang P, Wen J. Long-term efficacy of interferon alpha therapy on hepatitis B viral replication in patients with chronic hepatitis B: a meta-analysis. Antiviral Res. 2010;85:361–5.PubMedCrossRef
13.
go back to reference Suzuki F, Arase Y, Akuta N, Tsubota A, Suzuki Y, Sezaki H, et al. Efficacy of 6-month interferon therapy in chronic hepatitis B virus infection in Japan. J Gastroenterol. 2004;39:969–74.PubMedCrossRef Suzuki F, Arase Y, Akuta N, Tsubota A, Suzuki Y, Sezaki H, et al. Efficacy of 6-month interferon therapy in chronic hepatitis B virus infection in Japan. J Gastroenterol. 2004;39:969–74.PubMedCrossRef
14.
go back to reference Arase Y, Chayama K, Tsubota A, Murashima N, Suzuki Y, Koida I, et al. A randomized, double-blind, controlled trial of natural interferon-α therapy for e-antigen-negative chronic hepatitis B patients with abnormal transaminase levels. J Gastroenterol. 1996;31:559–64.PubMedCrossRef Arase Y, Chayama K, Tsubota A, Murashima N, Suzuki Y, Koida I, et al. A randomized, double-blind, controlled trial of natural interferon-α therapy for e-antigen-negative chronic hepatitis B patients with abnormal transaminase levels. J Gastroenterol. 1996;31:559–64.PubMedCrossRef
15.
go back to reference Arase Y, Tsubota A, Saitoh S, Suzuki Y, Kobayashi M, Suzuki F, et al. Randomized, controlled trial of natural interferon-α therapy for e-antigen-positive chronic hepatitis B patients. Hepatol Res. 2002;23:98–104.PubMedCrossRef Arase Y, Tsubota A, Saitoh S, Suzuki Y, Kobayashi M, Suzuki F, et al. Randomized, controlled trial of natural interferon-α therapy for e-antigen-positive chronic hepatitis B patients. Hepatol Res. 2002;23:98–104.PubMedCrossRef
16.
go back to reference Usuda S, Okamoto H, Imawari H, Baba K, Tsuda F, Miyakawa Y, et al. Serological detection of hepatitis B virus genotypes by ELISA with monoclonal antibodies to type-specific epitopes in preS2-region product. J Virol Method. 1999;80:97–112.CrossRef Usuda S, Okamoto H, Imawari H, Baba K, Tsuda F, Miyakawa Y, et al. Serological detection of hepatitis B virus genotypes by ELISA with monoclonal antibodies to type-specific epitopes in preS2-region product. J Virol Method. 1999;80:97–112.CrossRef
17.
go back to reference Tadokoro K, Kobayashi M, Yamaguchi T, Suzuki F, Miyauchi S, Egashira T, et al. Classification of hepatitis B virus genotypes by the PCR-Invader method with genotype-specific probes. J Virol Method. 2006;138:30–9.CrossRef Tadokoro K, Kobayashi M, Yamaguchi T, Suzuki F, Miyauchi S, Egashira T, et al. Classification of hepatitis B virus genotypes by the PCR-Invader method with genotype-specific probes. J Virol Method. 2006;138:30–9.CrossRef
18.
go back to reference Kobayashi M, Arase Y, Ikeda K, Tsubota A, Suzuki Y, Saitoh S, et al. Clinical characteristics of patients infected with hepatitis B virus genotypes A, B and C. J Gastroenterol. 2002;37:35–9.PubMedCrossRef Kobayashi M, Arase Y, Ikeda K, Tsubota A, Suzuki Y, Saitoh S, et al. Clinical characteristics of patients infected with hepatitis B virus genotypes A, B and C. J Gastroenterol. 2002;37:35–9.PubMedCrossRef
19.
go back to reference Niderau C, Heintges T, Lange S, Goldmann G, Niederau CM, Mohr L, et al. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J M. 1996;334:1422–7.CrossRef Niderau C, Heintges T, Lange S, Goldmann G, Niederau CM, Mohr L, et al. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J M. 1996;334:1422–7.CrossRef
20.
go back to reference Lin SM, Yu KL, Lee CM, Chien RN, Sheen IS, Chu CM, et al. Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol. 2007;46:45–52.PubMedCrossRef Lin SM, Yu KL, Lee CM, Chien RN, Sheen IS, Chu CM, et al. Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol. 2007;46:45–52.PubMedCrossRef
21.
go back to reference Papatheodoridis GV, Manesis E, Hadziyannis SJ. The long-term outcome of interferon-α treated and untreated patients with HBeAg-negative chronic hepatitis B. J Hepatol. 2001;34:306–13.PubMedCrossRef Papatheodoridis GV, Manesis E, Hadziyannis SJ. The long-term outcome of interferon-α treated and untreated patients with HBeAg-negative chronic hepatitis B. J Hepatol. 2001;34:306–13.PubMedCrossRef
22.
go back to reference Brunetto MR, Oliveri F, Coco B, Leandro G, Colombatto P, Gorin JM, et al. Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study. J Hepatol. 2002;36:263–70.PubMedCrossRef Brunetto MR, Oliveri F, Coco B, Leandro G, Colombatto P, Gorin JM, et al. Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study. J Hepatol. 2002;36:263–70.PubMedCrossRef
23.
go back to reference Lampertico P, Ninno ED, Vigano M, Romeo R, Donato MF, Sablon E, et al. Long-term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy. Hepatology. 2003;37:756–63.PubMedCrossRef Lampertico P, Ninno ED, Vigano M, Romeo R, Donato MF, Sablon E, et al. Long-term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy. Hepatology. 2003;37:756–63.PubMedCrossRef
24.
go back to reference Lau DTY, Everhart J, Kleiner DE, Park Y, Vergalla J, Schmid P, et al. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa. Gastroenterology. 1997;113:1660–7.PubMedCrossRef Lau DTY, Everhart J, Kleiner DE, Park Y, Vergalla J, Schmid P, et al. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa. Gastroenterology. 1997;113:1660–7.PubMedCrossRef
25.
go back to reference Kao JH, Wu NH, Chen PJ, Lai MY, Chen DS. Hepatitis B genotypes and the response to interferon therapy. J Hepatol. 2000;33:998–1002.PubMedCrossRef Kao JH, Wu NH, Chen PJ, Lai MY, Chen DS. Hepatitis B genotypes and the response to interferon therapy. J Hepatol. 2000;33:998–1002.PubMedCrossRef
26.
go back to reference Hadziyannis S, Bramou T, Makris A, Moussoulis G, Zignego L, Papaioannou C. Interferon alfa-2b treatment of HBeAg negative/serum HBV DNA positive chronic active hepatitis B. J Hepatol. 1990;11:S133–6.PubMedCrossRef Hadziyannis S, Bramou T, Makris A, Moussoulis G, Zignego L, Papaioannou C. Interferon alfa-2b treatment of HBeAg negative/serum HBV DNA positive chronic active hepatitis B. J Hepatol. 1990;11:S133–6.PubMedCrossRef
27.
go back to reference Pastore G, Santantonio T, Milella A, Monno L, Mariano N, Moschetta R, et al. Anti-HBe-positive chronic hepatitis B with HBV-DNA in serum: response to a 6-month course of lymphoblastoid interferon. J Hepatol. 1992;20:221–5.CrossRef Pastore G, Santantonio T, Milella A, Monno L, Mariano N, Moschetta R, et al. Anti-HBe-positive chronic hepatitis B with HBV-DNA in serum: response to a 6-month course of lymphoblastoid interferon. J Hepatol. 1992;20:221–5.CrossRef
28.
go back to reference Fattovich G, Farci P, Rugge M, Brollo G, Mandas A, Pontisso P, et al. A randomized, controlled trial of lymphoblastoid interferon-alfa in patients with chronic hepatitis B lacking HBeAg. Hepatology. 1992;15:584–9.PubMedCrossRef Fattovich G, Farci P, Rugge M, Brollo G, Mandas A, Pontisso P, et al. A randomized, controlled trial of lymphoblastoid interferon-alfa in patients with chronic hepatitis B lacking HBeAg. Hepatology. 1992;15:584–9.PubMedCrossRef
29.
go back to reference Lampertico P, Del Ninno E, Manzin A, Donato MF, Rumi MG, Lunghi G, et al. 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;26:1621–5.PubMedCrossRef Lampertico P, Del Ninno E, Manzin A, Donato MF, Rumi MG, Lunghi G, et al. 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;26:1621–5.PubMedCrossRef
30.
go back to reference Arase Y, Ikeda K, Suzuki F, Suzuki Y, Saitoh S, Kobayashi M, et al. Long-term outcome after hepatitis B surface antigen seroclearance in patients with chronic hepatitis B. Am J Med. 2006;119:71 e9–e16.PubMedCrossRef Arase Y, Ikeda K, Suzuki F, Suzuki Y, Saitoh S, Kobayashi M, et al. Long-term outcome after hepatitis B surface antigen seroclearance in patients with chronic hepatitis B. Am J Med. 2006;119:71 e9–e16.PubMedCrossRef
31.
go back to reference Kobayashi M, Suzuki F, Akuta N, Hosaka T, Sezaki H, Yatsuji H, et al. Loss of hepatitis B surface antigen from the serum of patients with chronic hepatitis treated with lamivudine. J Med Virol. 2007;79:1472–7.PubMedCrossRef Kobayashi M, Suzuki F, Akuta N, Hosaka T, Sezaki H, Yatsuji H, et al. Loss of hepatitis B surface antigen from the serum of patients with chronic hepatitis treated with lamivudine. J Med Virol. 2007;79:1472–7.PubMedCrossRef
Metadata
Title
Long-term efficacy of interferon therapy in patients with chronic hepatitis B virus infection in Japan
Authors
Fumitaka Suzuki
Yasuji Arase
Yoshiyuki Suzuki
Norio Akuta
Hitomi Sezaki
Yuya Seko
Yusuke Kawamura
Tetsuya Hosaka
Masahiro Kobayashi
Satoshi Saito
Kenji Ikeda
Mariko Kobayashi
Hiromitsu Kumada
Publication date
01-07-2012
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 7/2012
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-012-0548-5

Other articles of this Issue 7/2012

Journal of Gastroenterology 7/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine