Chronic hepatitis B: early viral suppression and long‐term outcomes of therapy with oral nucleos(t)ides

Summary.  Chronic hepatitis B is a serious health problem worldwide with a substantial minority of patients experiencing premature death due to end‐stage liver disease and/or hepatocellular carcinoma. Antiviral therapy may help prevent complications of chronic hepatitis B, and seven agents are currently approved in many countries. Of these agents, five are nucleos(t)ide analogs that all have a risk of antiviral drug resistance with long‐term use. Efforts have been made in the recent years to prevent or to reduce the risk of viral resistance in patients treated with oral nucleos(t)ides as the majority of these patients will require therapy for 3–5 years or longer. One approach is to identify patients who would most likely develop antiviral resistance on long‐term therapy using predictors obtainable early in the course of treatment, when intervention with new or additional therapy can be instituted. The most important predictors of treatment outcomes are serum HBV DNA levels at baseline and during the first 6 months of therapy. The purpose of this synopsis is to review the recent literature regarding the importance of serum HBV DNA levels in association with treatment outcomes in chronic hepatitis B, particularly the association of complete viral suppression early in the course of oral therapy with long‐term treatment outcomes, particularly the incidence of antiviral drug resistance.

[1]  Huy Trinh,et al.  Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. , 2008, The New England journal of medicine.

[2]  E. Schiff,et al.  A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[3]  M. Tong,et al.  Treatment recommendations for chronic hepatitis B: An evaluation of current guidelines based on a natural history study in the United States , 2008, Hepatology.

[4]  R. Colonno,et al.  Entecavir at Five Years Shows Long-Term Maintenance of High Genetic Barrier to Hepatitis B Virus Resistance , 2008 .

[5]  H. Tillmann,et al.  Telbivudine versus lamivudine in patients with chronic hepatitis B. , 2008, The New England journal of medicine.

[6]  S. Locarnini Primary resistance, multidrug resistance, and cross-resistance pathways in HBV as a consequence of treatment failure , 2008, Hepatology international.

[7]  P. Marcellin,et al.  Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial. , 2007, Annals of internal medicine.

[8]  M. Yuen,et al.  Hepatitis B virus DNA levels at week 4 of lamivudine treatment predict the 5‐year ideal response , 2007, Hepatology.

[9]  E. Keeffe,et al.  Report of an international workshop: Roadmap for management of patients receiving oral therapy for chronic hepatitis B. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[10]  A. Perelson,et al.  Impact of Early Viral Kinetics on T-Cell Reactivity during Antiviral Therapy in Chronic Hepatitis B , 2007, Antiviral therapy.

[11]  J. Sung,et al.  Early virological suppression is associated with good maintained response to adefovir dipivoxil in lamivudine resistant chronic hepatitis B , 2007, Alimentary pharmacology & therapeutics.

[12]  A. Lok,et al.  Navigating the maze of hepatitis B treatments. , 2007, Gastroenterology.

[13]  E. Keeffe,et al.  New and emerging treatment of chronic hepatitis B. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[14]  Y. Liaw,et al.  Chronic hepatitis B: treatment alert , 2006 .

[15]  George Kitis,et al.  Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. , 2006, Gastroenterology.

[16]  Sheng-Nan Lu,et al.  Virological Response and Incidence of Adefovir Resistance in Lamivudine-Resistant Patients Treated with Adefovir Dipivoxil , 2005, Antiviral therapy.

[17]  Y. Liaw,et al.  51 Optimal virologic and clinical efficacy at one year is associated with maximal early HBV suppression in nucleoside-treated hepatitis B patients , 2006 .

[18]  Chien-Jen Chen,et al.  Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. , 2006, Gastroenterology.

[19]  A. Lok,et al.  Natural history of chronic hepatitis B virus infection: What we knew in 1981 and what we know in 2005 , 2006, Hepatology.

[20]  Guan-Tarn Huang,et al.  Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. , 2006, JAMA.

[21]  P. Marcellin,et al.  A Randomized Trial of Telbivudine (LdT) vs Adefovir for HBeAg-positive Chronic Hepatitis B: Final Week 52 results , 2006 .

[22]  Graeme Currie,et al.  Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. , 2005, The New England journal of medicine.

[23]  J. Rodés,et al.  Severity of cholestasis and advanced histological stage but not menopausal status are the major risk factors for osteoporosis in primary biliary cirrhosis. , 2005, Journal of hepatology.

[24]  S. Pol [Epidemiology and natural history of hepatitis B]. , 2005, La Revue du praticien.

[25]  E. Keeffe,et al.  Management of Antiviral Resistance in Patients with Chronic Hepatitis B , 2004, Antiviral therapy.

[26]  D. Lavanchy,et al.  Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures , 2004, Journal of viral hepatitis.

[27]  P. Marcellin,et al.  Evolution of hepatitis B viral load and viral genome sequence during adefovir dipivoxil therapy , 2004, Journal of viral hepatitis.

[28]  M. Wulfsohn,et al.  Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. , 2003, The New England journal of medicine.

[29]  M. Wulfsohn,et al.  Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. , 2003, The New England journal of medicine.

[30]  E. Jury EASL International Consensus Conference on Hepatitis B. 13-14 September, 2002 Geneva, Switzerland. Consensus statement (long version). , 2003 .

[31]  A. Lok,et al.  EASL International Consensus Conference on Hepatitis B. 13-14 September, 2002 Geneva, Switzerland. Consensus statement (long version). , 2003, Journal of hepatology.

[32]  J. Petersen,et al.  Correlation of hepatitis B virus load with loss of e antigen and emerging drug‐resistant variants during lamivudine therapy , 2001, Journal of medical virology.

[33]  M. Yuen,et al.  Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy , 2001, Hepatology.

[34]  H. Kumada,et al.  [Chronic hepatitis B]. , 2001, Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology.