Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
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.
ADVANCED SEARCH
Log in
Top
Hepatology International
Published in: Hepatology International 2/2007

01-06-2007 | Original Paper

Chronic hepatitis B: a global health problem requiring coherent worldwide treatment strategies

Authors: George Lau, Patrick Marcellin, Marion Peters

Published in: Hepatology International | Issue 2/2007

Login to get access

Abstract

Chronic hepatitis B virus infection, a major cause of end-stage liver disease and hepatocellular carcinoma, is a worldwide health concern. While the past two decades have brought major advances in the availability of treatments to help delay or prevent these outcomes, treatment of chronic hepatitis B remains a serious challenge, not least due to the ability of the virus to remain in hepatocyte nuclei as a source of potential reactivation—hence the term chronic hepatitis B infection. This article reviews the current treatments available and suggests a framework for a rational approach to managing the disease.
Literature
1.
Hui CK, Lau GK. Current issues and future directions in treatment. Semin Liver Dis 2006;26(2):192–7.PubMedCrossRef
2.
Yim HJ, Lok AS. Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology 2006;43 2 Suppl 1:S173–81.PubMedCrossRef
3.
The EASL Jury. EASL consensus conference on hepatitis B. J Hepatol 2003;38:533–40.
4.
5.
Liaw Y-F, Leung N, Guan R, Lau GKK, Merican I, McCaughan G, Gane E, Kao J-H, Omata M for the Asian-Pacific consensus update working party on chronic hepatitis B. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update. Liver Int 2005;25:472–89.
6.
Keeffe EB, Dieterich DT, Han S-H, Jacobson IM, Martin P, Schiff ER, Tobias H, Wright TL. A treatment algorithm for the management of chronic hepatitis B virus in the United States: an update. Clin Gastroenterol Hepatol 2006;4:936–62.PubMedCrossRef
7.
Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment and current and emerging prevention and control measures. J Virol Hepat 2004;11:97–107.CrossRef
8.
WHO. The world health report. Geneva, Switzerland: World Health Organization; 1997.
9.
10.
11.
Chen C-J, Yang H-I, Su J, Jen C-L, You S-L, et al. Risk of HCC across a biological gradient of serum HBV DNA level. JAMA 2006;295:65–73.PubMedCrossRef
12.
Parkin DM, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001;92:153–6.CrossRef
13.
Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006;45:529–38.PubMedCrossRef
14.
Chen G, Lin W, Shen F, Iloeje UH, London WT. Chronic hepatitis B infection and mortality from non-liver causes: results from the Haimen cohort study. Intl J Epidemiol 2005;34:132–7.CrossRef
15.
Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000 – summary of a workshop. Gastroenterology 2001;120:1828–53.PubMedCrossRef
16.
17.
Chu CJ, Keeffe EB, Han SH, et al. Hepatitis B virus genotypes in the United States: results of a nationwide study. Gastroenterology 2003;125(2):444–51.PubMedCrossRef
18.
França HC, González JE, Silvina Munné M, Brandão LH, Gouvea VS, Sablon E, Bart OM. Vanderborght strong association between genotype F and hepatitis B virus (HBV) e antigen-negative variants among HBV-infected Argentinean blood donors. J Clin Microbiol 2004;42(11):5015–21.PubMedCrossRef
19.
Funk ML, Rosenberg DM, Lok ASF. World-wide epidemiology of HBeAg-negative chronic hepatitis B and associated precore and core promoter variants. J Viral Hepat 2002;9:52–61.PubMedCrossRef
20.
Mohamed R, Desmond P, Suh DJ, Amarapurkar D, Gane E, Guangbi Y, Hou JL, Jafri W, Lai CL, Lee CH, Lee SD, Lim SG, Guan R, Phiet PH, Piratvisuth T, Sollano J, Wu JC. Practical difficulties in the management of hepatitis B in the Asia-Pacific region. J Gastroenterol Hepatol 2004;19(9):958–69.PubMedCrossRef
21.
Fattovich G, Giustina G, Sanchez-Tapias J, Quero C, Mas A, Olivotto PG, Solinas A, Almasio P, Hadziyannis S, Degos F, de Moura MC, Krogsgaard K, Pantalena M, Realdi G, Corrocher R, Schalm SW. Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis. European concerted action on viral hepatitis (EUROHEP). Am J Gastroenterol 1998;93(6):896–900.PubMedCrossRef
22.
Fattovich G, Rugge M, Brollo L, Pontisso P, Noventa F, Guido M, Alberti A, et al. Clinical, virologic and histologic outcome following seroconversion from HBeAg to anti-HBe in chronic hepatitis type B. Hepatology 1986;6:167–72.PubMedCrossRef
23.
Niederau C, Heintges T, Lange S, Goldmann G, Niederau CM, Mohr L, Haussinger D. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med 1996;334:1422–7.PubMedCrossRef
24.
Wong DKH, Cheung AM, O’Rourke K, et al. Effect of alpha interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. Ann Intern Med 1993;119:312–23.PubMed
25.
Lok ASF, Lai CL, Wu PC, et al. Long-term follow-up in a randomised trial of recombinant alpha2-interferon in Chinese patients with chronic hepatitis B infection. Lancet 1988;2:298–302.PubMedCrossRef
26.
Bortolotti F, Jara P, Barbera C, et al. Long term effect of alpha interferon in children with chronic hepatitis B. Gut 2000;46:715–8.PubMedCrossRef
27.
Korenman J, Baker B, Waggoner J, Everhart JE, Di Bisceglie AM, Hoofnagle JH. Long-term remission of chronic hepatitis B after alpha-interferon therapy. Ann Intern Med 1991;114(8):629–34.PubMed
28.
Lin SM, Yu ML, Lee CM, Chien RN, Sheen IS, Chu CM, Liaw YF. Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol 2007;46(1):45–52.PubMedCrossRef
29.
Hadziyannis SJ. Hepatitis B e antigen negative chronic hepatitis B: from clinical recognition to pathogenesis and treatment. Viral Hep Rev 1995;1:7–36.
30.
Marcellin P, Lau GK, Bonino F, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2004;351:1206–17.PubMedCrossRef
31.
Lau GK, Piratvisuth YT, Luo KX, et al. Peginterferon alfa-2a, lamivudine and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med 2005;352:2682–95.PubMedCrossRef
32.
Cooksley WG, Piratvisuth T, Lee SD, Mahachai V, Chao YC, Tanwandee T, Chutaputti A, Chang WY, Zahm FE, Pluck N. Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. J Viral Hepat 2003;10(4):298–305.PubMedCrossRef
33.
Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, Gane E, Fried MW, Popescu M, Wu J. Durability of response and occurrence of late response to peginterferon-alpha-2a (40 KD) [PEGASYS] one year post-treatment inpatients with HBeAg-positive chronic hepatitis B. J Hepatol 2006;44 Suppl 2:S23 (Abstract 50).CrossRef
34.
Janssen HL, van Zonneveld M, Senturk H, Zeuzem S, Akarca US, Cakaloglu Y, Simon C, So TM, Gerken G, de Man RA, Niesters HG, Zondervan P, Hansen B, Schalm SW, HBV 99-01 Study Group, Rotterdam Foundation for Liver Research. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet 2005;365(9454):123–9.
35.
Marcellin P, Bonino F, Lau GK, Farci P, Yurdaydin C, Piratvisuth T, Jin R, Gurel S, Hadziyannis S, Lu Z-M, Popescu M. The majority of patients with HBeAg-negative chronic hepatitis B treated with peginterferon-alpha-2a (40 KD) [PEGASYS] sustain response 2 years post-treatment. J Hepatol 2006;44 Suppl 2:S274 (Abstract 743).
36.
Liaw YF. Results of lamivudine in Asian trials. Proceedings of EASL international consensus conference on hepatitis B: 2002. J Hepatol 2003;39:S111–5.
37.
Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, Dienstag JL, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology 2003;125:1714–22.PubMedCrossRef
38.
Tassopoulos NC, Volpes R, Pastore G, Heathcote J, Buti M, Goldin RD, Hawley S, et al. Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Study Group. Hepatology 1999;29:889–96.PubMedCrossRef
39.
Santantonio T, Mazzola M, Iacovazzi T, Miglietta A, Guastadisegni A, Pastore G. Long-term follow-up of patients with anti-HBe/HBV DNA-positive chronic hepatitis B treated for 12 months with lamivudine. J Hepatol 2000;32:300–6.PubMedCrossRef
40.
Rizzetto M, Marzano A, Lagget M. Treatment of hepatitis B e antigen-negative chronic hepatitis B with lamivudine. J Hepatol 2003;39:S168–71.PubMedCrossRef
41.
Lampertico P, Vigano M, Iavarone M, Lunghi G, Romeo R, Colucci G, Morabito A, Del Nino E, Columbo M. The long-term outcome of HBeAg-negative patients with cirrhosis treated with lamivudine monotherapy: a five-year prospective cohort study. J Hepatol 2004; Abstract 44.
42.
Liaw Y. Management of YMDD mutations during lamivudine therapy in patients with chronic hepatitis B. J Gastroenterol Hepatol 2002;17:S333–7.PubMedCrossRef
43.
Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Brosgart CL, Borroto-Esoda K, Arterburn S, Chuck SL, Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology 2006;131(6):1743–51.
44.
Locarnini S, Qi X, Arterburn S, Snow A, Brosgart CL, Currie G, Wulfsohn M, Miller M, Xiong S. Incidence and predictors of emergence of HBV mutations associated with adefovir resistance during 4 years of adefovir therapy for patients with chronic hepatitis B. 40th EASL Meeting, 2005, Paris, France. Oral # 36.
45.
Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Adefovir dipivoxil for the treatment of HBeAg-negative chronic hepatitis B. N Engl J Med 2003;348:800–7.PubMedCrossRef
46.
Hadziyannis S, Tassopoulos NC, Chang TT, et al. Long-term adefovir dipivoxil treatment induces regression of liver fibrosis in patients with HBeAg-negative chronic hepatitis B: results after 5 years of therapy. Hepatology 2005;42 Suppl 1:754A.
47.
Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med 2006;354:1001–10.PubMedCrossRef
48.
Lai CL, Shouval D, Lok AS, et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2006;354:1011–20.PubMedCrossRef
49.
Bzowej N, Lai C, Gane L, et al. Phase III comparison of telbivudine vs lamivudine in patients with chronic hepatitis B: efficacy, safety, and predictors of response at 1 year [Abstract]. Gastroenterology 2006;130 Suppl 2:A765–6.
50.
Jones R, Nelson M. Novel anti-hepatitis B agents: a focus on telbivudine. Int J Clin Pract 2006;60(10):1295–9.PubMedCrossRef
51.
Heathcote E, Chan H, Cho M, et al. A randomized trial of telbivudine (LdT) vs. adefovir for HBeAg-positive chronic hepatitis B: results of the primary week 24 analysis [Abstract]. Gastroenterology 2006;130 Suppl 2:A765.
52.
Marcellin P, Mommeja-Marin H, Sacks SL, Lau GK, Sereni D, Bronowicki JP, Conway B, Trepo C, Blum MR, Yoo BC, Mondou E, Sorbel J, Snow A, Rousseau F, Lee HS. A phase II dose-escalating trial of clevudine in patients with chronic hepatitis B. Hepatology 2004;40(1):140–8.PubMedCrossRef
53.
Hui CK, Lau GK. Clevudine for the treatment of chronic hepatitis B virus infection. Expert Opin Investig Drugs 2005;14(10):1277–84.PubMedCrossRef
54.
Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, Yu CF, Walsh A, Fang J, Hsu M, Mazzucco C, Eggers B, Zhang S, Plym M, Klesczewski K, Tenney DJ. Entecavir resistance is rare in nucleoside naive patients with hepatitis B. Hepatology 2006;44(6):1656–65.PubMedCrossRef
55.
Tenney DJ, Levine SM, Rose RE, et al. Clinical emergence of entecavir resistant hepatitis B virus requires additional substitutions in virus already resistant to Lamivudine. Antimicrob Agents Chemother 2004;48:3498–507.PubMedCrossRef
56.
van Boemmel F, Mauss S, Shuermann D, et al. No evidence for tenefovir resistance in patients with lamivudine-resistant HBV infection during long-term treatment for up to 5 years. Hepatol 2006;44(4):549A.
57.
Lim SG, Krastev Z, Ng TM, et al. Randomized, double-blind study of emtricitabine (FTC) plus clevudine versus FTC alone in treatment of chronic hepatitis B. Antimicrob Agents Chemother 2006;50:1642–8.PubMedCrossRef
58.
Lee YS, Suh DJ, Lim YS, Jung SW, Kim KM, Lee HC, Chung YH, Lee YS, Yoo W, Kim SO. Increased risk of adefovir resistance in patients with lamivudine-resistantchronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy. Hepatology 2006;43(6):1385–91.PubMedCrossRef
59.
Dan Y, Wai C, Lim S. Modeling for the most cost-effective treatment strategy for eAg positive chronic hepatitis B. Hepatology 2006 (Abstract).
60.
Shibolet O, Ilan Y, Gillis S, Hubert A, Shouval D, Safadi R. Lamivudine therapy for prevention of immunosuppressive-induced hepatitis B virus reactivation in hepatitis B surface antigen carriers. Blood 2002;100:391–6.PubMedCrossRef
61.
Yeo W, Chan PK, Ho WM, et al. Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy. J Clin Oncol 2004;22:927–34.PubMedCrossRef
62.
van Zonneveld M, van Nunen AB, Niesters HG, de Man RA, Schalm SW, Janssen HL. Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection. J Viral Hepat 2003;10:294–7.PubMedCrossRef
63.
McMahon BJ. Selecting appropriate management strategies for chronic hepatitis B: who to treat. Am J Gastroenterol 2006;101 Suppl 1:S7–12.PubMedCrossRef
64.
Perrillo RP. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology 2001;120(4):1009–22.PubMedCrossRef
65.
Perrillo RP, Lai CL, Liaw YF, Dienstag JL, Schiff ER, Schalm SW, Heathcote EJ, Brown NA, Atkins M, Woessner M, Gardner SD. Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B. Hepatology 2002;36(1):186–94.PubMedCrossRef
66.
Yim HJ, Hussain M, Liu Y, Wong SN, Fung SK, Lok AS. Evolution of multi-drug resistant hepatitis B virus during sequential therapy. Hepatology 2006;44(3):703–12.PubMedCrossRef
67.
Lai CL, Leung N, Teo EK, Tong M, Wong F, Hann HW, Han S, Poynard T, Myers M, Chao G, Lloyd D, Brown NA, Telbivudine Phase II Investigator Group. A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B. Gastroenterology 2005;129(2):528–36.
Metadata
Title
Chronic hepatitis B: a global health problem requiring coherent worldwide treatment strategies
Authors
George Lau
Patrick Marcellin
Marion Peters
Publication date
01-06-2007
Publisher
Springer-Verlag
Published in
Hepatology International / Issue 2/2007
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-007-9006-5

Other articles of this Issue 2/2007

Hepatology International 2/2007 Go to the issue

Original Paper

Interferon-beta is activated by hepatitis C virus NS5B and inhibited by NS4A, NS4B, and NS5A

Editorial

Unrevealing the natural course of the so-called “inactive HBsAg or HBV carrier state”

Original Paper

Spontaneous relapse of hepatitis in inactive HBsAg carriers

Editorial Notes

Towards a rational treatment strategy for chronic hepatitis B

Events

The 17th APASL Annual Meeting 2007 at Kyoto

Original Paper

Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

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

Read more

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

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits