The clinical and epidemiological importance of chronic B hepatitis is currently unquestionable as a cause of end-stage liver disease and hepatocellular carcinoma. Recently, predictors of treatment response of this disease have been studied, both before and during the course of medication. Therapy stopping rules have been proposed, which may be useful in patients presenting poor treatment tolerance. This review discusses the treatment response predictors usefulness, with emphasis on ALT, quantitative HBsAg and HBeAg, quantitative HBV-DNA and HBV genotype.
Journal Information
Vol. 14. Issue 5.
Pages 519-525 (September - October 2010)
Vol. 14. Issue 5.
Pages 519-525 (September - October 2010)
Review article
Open Access
Response predictors to treatment with pegylated interferon in chronic hepatitis B
Visits
2691
Paulo Roberto Abrão Ferreira1,
, Simone de Barros Tenore2
Corresponding author
paulo.abrao.ferreira@gmail.com
Correspondence to: Rua Ouvidor Peleja, 235, ap 101 Vila Mariana - São Paulo – SP – Brazil CEP: 04128000.
Correspondence to: Rua Ouvidor Peleja, 235, ap 101 Vila Mariana - São Paulo – SP – Brazil CEP: 04128000.
1 Physician of the HIV and Viral Hepatitis Outpatient Clinic of the Discipline of Infectious Diseases of UNIFESP; Member of the Viral Hepatitis Group of CRT STD-Aids in São Paulo - Brazil
2 Master's Degree in Infectology by UNIFESP; Assisting Physician at HIV and Hepatitis Outpatient Clinic at UNIFESP; Physician of the Viral Hepatitis Group at CRT DST-Aids in São Paulo - Brazil
This item has received
Article information
Abstract
Keywords:
hepatitis B
HBsAg
HBeAg
HBV-DNA
pegylated interferon
Full text is only aviable in PDF
References
[1.]
H.L.Y. Chan, J.J.Y. Sung.
Hepatocellular carcinoma and hepatitis B virus.
Semin Liver Dis, 26 (2006), pp. 153-161
[2.]
E.B. Keeffe, S. Zeuzem, R.S. Koff, et al.
Report of an international workshop: roadmap for management of patients receiving oral therapy for chronic hepatitis B.
Clin Gastroenterol Hepatol, 5 (2007), pp. 890-897
[3.]
A.S. Lok, B.J. McMahon.
Chronic hepatitis B.
Hepatology, 45 (2007), pp. 507-539
[4.]
European Association for the Study of the Liver.
EASL Clinical practice guidelines: management of chronic hepatitis B.
J Hepatol, 50 (2009), pp. 227-242
[5.]
Y.F. Liaw, N.W. Leung, J.H. Kao, et al.
Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update.
Hepatol Int, 2 (2008), pp. 263-283
[6.]
M.F. Yuen, D.K. Wong, J. Fung, et al.
HBsAg seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma.
Gastroenterology, 135 (2008), pp. 1192-1199
[7.]
M. Lutgehetmann, T. Volzt, A. Quaas, et al.
Sequential combination therapy leads to biochemical and histological improvement despite low ongoing intrahepatic hepatitis B virus replication.
Antivir Ther, 13 (2008), pp. 57-66
[8.]
C. Niederau, T. Heintges, S. Lange, et al.
Long-term follow-up of HBeAg-positive patients treated with interferon alpha for chronic hepatitis B.
N Engl J Med, 334 (1996), pp. 1422-1427
[9.]
F.E. de Jongh, H.L. Janssen, R.A. de Man, et al.
Survival and prognostic indicators in hepatitis B surface antigen positive cirrhosis of the liver.
Gastroenterology, 103 (1992), pp. 1630-1635
[10.]
D.T. Lau, J. Everhart, D.E. Kleiner, et al.
Long-term follow-up of patients with chronic hepatitis B treated with interferon alpha.
Gastroenterology, 113 (1997), pp. 1660-1667
[11.]
Y.F. Liaw, J.J. Sung, W.C. Chow, et al.
Lamivudine for patients with chronic hepatitis B and advanced liver disease.
N Engl J Med, 351 (2004), pp. 1521-1531
[12.]
A.S. Lok, C.L. Lai, P.C. Wu, et al.
Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection.
Gastroenterology, 92 (1987), pp. 1839-1843
[13.]
A.S. Lok, C.L. Lai.
Acute exacerbations in Chinese patients with chronic hepatitis B virus (HBV) infection: incidence, predisposing factors and etiology.
J Hepatol, 10 (1990), pp. 29-34
[14.]
Y.S. Hsu, R.N. Chien, C.T. Yeh, et al.
Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B.
Hepatology, 35 (2002), pp. 1522-1527
[15.]
H.L.Y. Chan, A.Y. Hui, V.W.S. Wong, et al.
Long-term follow up of peginterferon and lamivudine combination treatment in HBeAg-positive chronic hepatitis B.
Hepatology, 41 (2005), pp. 1357-1364
[16.]
A.B. van Nunen, B.E. Hansen, D.J. Suh, et al.
Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase.
Gut, 52 (2003), pp. 420-424
[17.]
C.J. Chen, H.I. Yang, J. Su, et al.
Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.
JAMA, 295 (2006), pp. 65-73
[18.]
H.L.Y. Chan, C.H. Tse, F. Mo, et al.
High viral load and hepatitis B virus subgenotype Ce are associated with increased risk of hepatocellular carcinoma.
J Clin Oncol, 26 (2008), pp. 177-182
[19.]
G.V. Papatheodoridis, E. Dimou, K. Dimakopoulos, et al.
Outcome of hepatitis B e antigen-negative chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine.
Hepatology, 42 (2005), pp. 121-129
[20.]
V. Di Marco, A. Marzano, P. Lampertico, et al.
Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine.
Hepatology, 40 (2004), pp. 883-891
[21.]
J.J.Y. Sung, K.K.F. Tsoi, V.W.S. Wong, et al.
Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma.
Aliment Pharmacol Ther, 28 (2008), pp. 1067-1077
[22.]
Wong VWS, Wong GLH, Chim AML et al. Surrogate endpoints and long-term outcome in patients with chronic hepatitis B. Clin Gastroenterol Hepatol 2009 [Epub ahead of publ].
[23.]
S.J. Hadziyannis, N.C. Tassopoulos, E.J. Heathcote, et al.
Long-term therapy with adefovir dipivoxil for HBeAg negative chronic hepatitis B.
N Engl J Med, 352 (2005), pp. 2673-2681
[24.]
P. Marcellin, F. Bonino, G.K. Lau, et al.
Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a.
Gastroenterology, 136 (2009), pp. 2169-2179
[25.]
A.S. Lok, C.L. Lai, N. Leung, et al.
Long- term safety of lamivudine treatment in patients with chronic hepatitis B.
Gastroenterology, 125 (2003), pp. 1714-1722
[26.]
J.L. Dienstag, J. Cianciara, S. Karayalcin, et al.
Durability of serologie response after lamivudine treatment of chronic hepatitis B.
Hepatology, 37 (2003), pp. 748-755
[27.]
H.L.Y. Chan, V.W.S. Wong, C.H. Tse, et al.
Early virological suppression is associated with good maintained response to adefovir dipivoxil in lamivudine resistant chronic hepatitis B.
Aliment Pharmacol Ther, 25 (2007), pp. 891-898
[28.]
P. Lampertico, M. Vigano, E. Manenti, et al.
Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients.
Gastroenterology, 133 (2007), pp. 1445-1451
[29.]
A.D. Min, J.L. Dienstag.
Oral antivirals for chronic hepatitis B.
Clin Liver Dis, 11 (2007), pp. 851-868
[30.]
E.H. Buster, H.J. Flink, Y. Cakaloglu, et al.
Sustained HbeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b.
Gastroenterology, 135 (2008), pp. 459-467
[31.]
G. Fattovich, G. Giustina, G. Realdi, et al.
Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alpha. European Concerted Action on Viral Hepatitis (EUROHEP).
Hepatology, 26 (1997), pp. 1338-1342
[32.]
S.M. Lin, I.S. Sheen, R.N. Chien, et al.
Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection.
Hepatology, 29 (1999), pp. 971-975
[33.]
A.S. Lok, H.T. Chung, V.W. Liu, et al.
Long-term follow-up of chronic hepatitis B patients treated with interferon alpha.
Gastroenterology, 105 (1993), pp. 1833-1838
[34.]
J. Korenman, B. Baker, J. Waggoner, et al.
Long-term remission of chronic hepatitis B after alpha interferon therapy.
Ann Intern Med, 114 (1991), pp. 629-634
[35.]
R. Moucari, A. Korevaar, O. Lada, et al.
High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study.
J Hepatol, 50 (2009), pp. 1084-1092
[36.]
T.T. Chang, C.L. Lai, R.N. Chien, et al.
Four years of lamivudine treatment in Chinese patients with chronic hepatitis B.
J Gastroenterol Hepatol, 19 (2004), pp. 1276-1282
[37.]
S.J. Hadziyannis, N.C. Tassopoulos, E.J. Heathcote, et al.
Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years.
Gastroenterology, 131 (2006), pp. 1743-1751
[38.]
R. Gish, T.T. Chang, R. de Man, et al.
Entecavir results in substantial virologic and biochemical improvement and HBeAg seroconversion through 96 weeks of treatment in HBeAg(+) Chronic hepatitis B patients (Study ETV-022) [Abstract].
Hepatology, 42 (2005), pp. 267A
[39.]
T.T. Chang, Y.C. Chao, S. Kaymakoglu, et al.
Entecavir maintained virologic suppression through 3 years of treatment in antiviral-naive HBeAg(+) patients (ETV 022/901) [abstract].
Hepatology, 44 (2006), pp. 229A
[40.]
C.L. Lai, E. Gane, C-W. Hsu, et al.
Two-year results from the GLOBE trial in patients with hepatitis B: greater clinical and antiviral efficacy for telbivudine (LdT) vs. lamivudine [abstract].
Hepatology, 44 (2006), pp. 222A
[41.]
Z.M. Younossi, Y. Benhamou, E.J. Gane, et al.
Lack of influence of baseline genotype on antiviral response in subjects with chronic hepatitis B infection receiving tenofovir DF 300 mg QD for 1 year [abstract].
Gastroenterology, 134 (2008), pp. 8O9A
[42.]
C.L. Lai, J. Dienstag, E. Schiff, et al.
Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B.
Clin Infect Dis, 36 (2003), pp. 687-696
[43.]
M.G. Ghany, D.B. Strader, D.L. Thomas, et al.
Diagnosis, management, and treatment of hepatitis C: an update.
Hepatology, 49 (2009), pp. 1335-1374
[44.]
H.L.Y. Chan, G.L.H. Wong, V.W.S. Wong.
A review of the natural history of chronic hepatitis B in the era of transient elastography.
Antivir Ther, 14 (2009), pp. 489-499
[45.]
G.K. Lau, T. Piratvisuth, K.X. Luo, et al.
Peginterferon alpha-2a, lamivudine and the combination for HBeAg-positive chronic hepatitis B.
N Engl J Med, 352 (2005), pp. 2682-2695
[46.]
H.L. Janssen, M. van Zonneveld, H. Senturk, et al.
Pegylated interferon alpha-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial.
Lancet, 365 (2005), pp. 123-129
[47.]
A. Erhardt, D. Blondin, K. Hauck, et al.
Response to interferon alpha is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D.
Gut, 54 (2005), pp. 1009-1013
[48.]
A.S. Lok, P.C. Wu, C.L. Lai, et al.
A controlled trial of interferon with or without prednisone priming for chronic hepatitis B.
Gastroenterology, 102 (1992), pp. 2091-2097
[49.]
R.P. Perrillo, E.R. Schiff, G.L. Davis, et al.
A randomized, controlled trial of interferon alpha-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional Therapy Group.
N Engl J Med, 323 (1990), pp. 295-301
[50.]
F. Bonino, P. Marcellin, G.K. Lau, et al.
Predicting response to peginterferon alpha-2a, lamivudine and the two combined for HBcAg-negative chronic hepatitis B.
Gut, 56 (2007), pp. 699-705
[51.]
H.L.Y. Chan, V.W.S. Wong, A.M. Tse, et al.
Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response.
Clin Gastroenterol Hepatol, 5 (2007), pp. 1462-1468
[52.]
H.L.Y. Chan, V.W.S. Wong, A.M.L. Chim, et al.
Virological response to different combination regimens of peginterferon alpha-2b and lamivudine in hepatitis B e antigen positive chronic hepatitis B.
Antivir Ther, 12 (2007), pp. 815-823
[53.]
B. Takkenberg, H. Zaaijer, C. Weegink, et al.
Baseline HbsAg level predict HBsAg loss in chronic hepatitis B patients treated with a combination of peginterferon alpha-2a and adefovir: an interim analysis.
J Hepatol, 50 (2009), pp. S8
[54.]
G.K. Lau, P. Marcellin, M. Brunetto, et al.
On-treatment HBsAg decline during peginterferon alpha-2a (40KD) +/- lamivudine in patients with HBeAg-positive CHB as a potential predictor of durable off-treatment response [abstract].
Hepatology, 48 (2008), pp. 714A
[55.]
B. Wcrle-Lapostolle, S. Bowden, S. Locarnini, et al.
Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy.
Gastroenterology, 126 (2004), pp. 1750-1758
[56.]
M.J. ter Borg, M. van Zonneveld, S. Zeuzem, et al.
Patterns of viral decline during peginterferon alpha-2b therapy in HBeAgpositive chronic hepatitis B: relation to treatment response.
Hepatology, 44 (2006), pp. 721-727
[57.]
P. Farci, P. Marcellin, Z.M. Lu, et al.
On-treatment predictors of sustained biochemical and virological response in patients with HBeAg-negative chronic hepatitis B (CHB) treated with peginterferon alpha-2a (40kDa) (Pegasys®) [abstract].
J Hepatol, 42 (2005), pp. 175A
[58.]
H.L.Y. Chan, V.W.S. Wong, A.M.L. Chim, et al.
Treatment of patients with chronic hepatitis B who have failed previous antiviral treatment with pegylated interferon alpha-2a (40kda; PEGASYS).
Antivir Ther, 13 (2008), pp. 555-562
[59.]
H.L.Y. Chan, N.W.Y. Leung, A.Y. Hui, et al.
A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferon-a2b and lamivudine with lamivudine alone.
Ann Intern Med, 142 (2005), pp. 240-250
[60.]
H.L.Y. Chan, V.W.S. Wong, G.L.H. Wong, et al.
Early hepatitis B virus DNA suppression can predict virologie response to peginterferon and lamivudine treatment.
Clin Gastroenterol Hepatol, 6 (2008), pp. 1022-1026
[61.]
M.W. Fried, T. Piratvisuth, G.K. Lau, et al.
HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alpha-2a for HBeAg-positive chronic hepatitis B.
Hepatology, 47 (2008), pp. 428-434
[62.]
R. Moucari, V. Mackiewicz, O. Lada, et al.
Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alpha-2a in HBeAg-negative patients.
Hepatology, 49 (2009), pp. 1151-1157
[63.]
M.R. Brunetto, F. Moriconi, F. Bonino, et al.
Hepatitis B virus surface antigen levels: a guide to sustained response to peginterferon alpha-2a in HBeAg-negative chronic hepatitis B.
Hepatology, 49 (2009), pp. 1141-1150
[64.]
P. Marcellin, M. Brunetto, F. Bonino, et al.
In patients with HbeAg-negative chronic hepatitis B HBsAg serum levels early during treatment with peginterferon alpha-2a predict H BsAg clearance 4 years postreatment [abstract].
Hepatology, 48 (2008), pp. 7I8A
[65.]
S.M. Lin, M.L. Yu, C.M. Lee, et al.
Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma.
J Hepatol, 46 (2007), pp. 45-52
[66.]
M. van Zonneveld, P. Honkoop, B.E. Hansen, et al.
Long-term follow-up of alphainterferon treatment of patients with chronic hepatitis B.
Hepatology, 39 (2004), pp. 804-810
Copyright © 2010. Elsevier Editora Ltda.. All rights reserved