The role of quantitative hepatitis B surface antigen revisited.

In the past 10years, there has been a lot of enthusiasm surrounding the use of serum hepatitis B surface antigen (HBsAg) quantification to predict disease activity and monitor treatment response in chronic hepatitis B. The measurement of HBsAg levels have been standardized in IU/ml, and nowadays it is almost a mandatory measurement due to the development of new antiviral treatments aiming at HBsAg seroclearance, i.e., functional cure of hepatitis B. Recently, there has been an improved understanding of the molecular virology of HBsAg, and particularly the relative roles of covalently closed circular DNA and integrated hepatitis B virus (HBV) DNA. This has shed new light on the interpretation of HBsAg levels in different phases of chronic hepatitis B. HBsAg level can assist the differentiation of immune tolerance and immune clearance in hepatitis B e antigen (HBeAg)-positive patients, and it can predict inactive disease and spontaneous HBsAg seroclearance in HBeAg-negative patients. The determination of HBsAg level is pivotal to individualize pegylated interferon (PegIFN) treatment; it is the key investigation to decide early termination of PegIFN among non-responders. Among patients treated by nucleos(t)ide analogues, responders tend to have dramatic reduction of HBsAg to low levels, which may be followed by HBsAg seroclearance. With newer data on combination treatment of PegIFN and nucleos(t)ide analogues as well as emerging new antiviral agents, HBsAg quantification is expected to become increasingly important to monitor and guide antiviral therapy for chronic hepatitis B.

[1]  H. Wedemeyer,et al.  Hepatitis delta virus , 2011, The Lancet.

[2]  V. Wong,et al.  Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study , 2014, Gut.

[3]  G. Gerken,et al.  Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial , 2005, The Lancet.

[4]  H. Janssen,et al.  Measurement of HBsAg to monitor hepatitis B viral replication in patients on alpha-interferon therapy. , 1994, Antiviral research.

[5]  Ding‐Shinn Chen,et al.  Serum hepatitis B surface antigen levels help predict disease progression in patients with low hepatitis B virus loads , 2013, Hepatology.

[6]  Ding‐Shinn Chen,et al.  Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. , 2011, Gastroenterology.

[7]  Liang Yu,et al.  Hepatitis B surface antigen levels during natural history of chronic hepatitis B: a Chinese perspective study. , 2014, World journal of gastroenterology.

[8]  M. Brunetto,et al.  Hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers. , 2010, Gastroenterology.

[9]  Sheng-Nan Lu,et al.  Prediction models of long‐term Cirrhosis and hepatocellular carcinoma risk in chronic hepatitis B patients: Risk scores integrating host and virus profiles , 2013, Hepatology.

[10]  R. D. de Man,et al.  Hepatitis B surface antigen declines and clearance during long-term tenofovir therapy in patients coinfected with HBV and HIV. , 2012, The Journal of infectious diseases.

[11]  W. Gerlich,et al.  Analysis of viral proteins in circulating immune complexes from chronic carriers of hepatitis B virus. , 1991, Clinical and experimental immunology.

[12]  EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. , 2012, Journal of hepatology.

[13]  C. Boucher,et al.  Serum HBsAg decline during long-term potent nucleos(t)ide analogue therapy for chronic hepatitis B and prediction of HBsAg loss. , 2011, The Journal of infectious diseases.

[14]  Chien-Jen Chen,et al.  Serum Levels of Hepatitis B Surface Antigen and DNA Can Predict Inactive Carriers With Low Risk of Disease Progression , 2016, Hepatology.

[15]  Thomas Berg,et al.  Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. , 2005, The New England journal of medicine.

[16]  A. Alibrandi,et al.  Impact of hepatitis B virus (HBV) preS/S genomic variability on HBV surface antigen and HBV DNA serum levels , 2012, Hepatology.

[17]  V. Wong,et al.  Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg‐negative patients , 2010, Journal of medical virology.

[18]  S. Sarin,et al.  Relevance of hepatitis B surface antigen levels in patients with chronic hepatitis B during 5 year of tenofovir treatment , 2014, Journal of viral hepatitis.

[19]  Y. Liaw,et al.  Response‐guided peginterferon therapy in hepatitis B e antigen‐positive chronic hepatitis B using serum hepatitis B surface antigen levels , 2013, Hepatology.

[20]  W. Gerlich,et al.  [Prognostic significance of quantitative HBsAg determination in acute hepatitis B. Partial report of a cooperative clinical study of the DFG-focus of "virus hepatitis"]. , 1977, Verhandlungen der Deutschen Gesellschaft fur Innere Medizin.

[21]  N. Warner,et al.  Article Commentary: Can Antiviral Therapy for Chronic Hepatitis B Enhance the Progression to Hepatocellular Carcinoma? , 2009, Antiviral therapy.

[22]  V. Wong,et al.  A Randomized, Controlled Trial of Combination Therapy for Chronic Hepatitis B: Comparing Pegylated Interferon-2b and Lamivudine with Lamivudine Alone , 2005, Annals of Internal Medicine.

[23]  N. Izumi,et al.  Influence of hepatitis B virus genotypes on the intra‐ and extracellular expression of viral DNA and antigens , 2006, Hepatology.

[24]  M. Yuen,et al.  Quantitative Hepatitis B Surface Antigen Levels in Patients With Chronic Hepatitis B After 2 Years of Entecavir Treatment , 2011, The American Journal of Gastroenterology.

[25]  P. Banerjee,et al.  Immune-driven adaptation of hepatitis B virus genotype D involves preferential alteration in B-cell epitopes and replicative attenuation--an insight from human immunodeficiency virus/hepatitis B virus coinfection. , 2015, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[26]  A. Lok,et al.  Strategies to control hepatitis B: Public policy, epidemiology, vaccine and drugs. , 2015, Journal of hepatology.

[27]  J. Summers,et al.  Genomic DNA double-strand breaks are targets for hepadnaviral DNA integration. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[28]  S. Locarnini,et al.  The covalently closed duplex form of the hepadnavirus genome exists in situ as a heterogeneous population of viral minichromosomes , 1995, Journal of virology.

[29]  V. Bruss.  Hepatitis B virus morphogenesis. , 2007, World journal of gastroenterology.

[30]  M. Manns,et al.  Treatment of HBV/HCV coinfection , 2010, Expert opinion on pharmacotherapy.

[31]  W. Gerlich,et al.  Standardized detection of hepatitis B surface antigen: determination of its serum concentration in weight units per volume. , 1975, Developments in biological standardization.

[32]  C. Delaugerre,et al.  Kinetics of hepatitis B surface and envelope antigen and prediction of treatment response to tenofovir in antiretroviral-experienced HIV–hepatitis B virus-infected patients , 2012, AIDS.

[33]  P. Marcellin,et al.  Hepatitis B virus surface antigen levels: A guide to sustained response to peginterferon alfa‐2a in HBeAg‐negative chronic hepatitis B , 2009, Hepatology.

[34]  D. Vassilopoulos,et al.  Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir. , 2012, Gastroenterology.

[35]  Ding‐Shinn Chen,et al.  Determinants of spontaneous surface antigen loss in hepatitis B e antigen–negative patients with a low viral load , 2012, Hepatology.

[36]  Soon Sun Kim,et al.  Correlation of serum hepatitis B surface antigen level with response to entecavir in naïve patients with chronic hepatitis B , 2011, Journal of medical virology.

[37]  John F. Flaherty,et al.  Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive chronic hepatitis B treated with tenofovir disoproxil fumarate. , 2014, Journal of hepatology.

[38]  V. Wong,et al.  Viral determinants of hepatitis B surface antigen seroclearance in hepatitis B e antigen-negative chronic hepatitis B patients. , 2011, The Journal of infectious diseases.

[39]  C. Rogler,et al.  Duck hepatitis B virus integrations in LMH chicken hepatoma cells: identification and characterization of new episomally derived integrations , 1995, Journal of virology.

[40]  M. Yuen,et al.  Hepatitis B Surface Antigen Seroclearance: Relationship to Hepatitis B e-Antigen Seroclearance and Hepatitis B e-Antigen-Negative Hepatitis , 2014, The American Journal of Gastroenterology.

[41]  V. Wong,et al.  A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B , 2010, Hepatology.

[42]  P. Marcellin,et al.  Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. , 2004, The New England journal of medicine.

[43]  J. Stockman,et al.  Peginterferon Alfa-2a, Lamivudine, and the Combination for HBeAg-Positive Chronic Hepatitis B , 2007 .

[44]  M. Manns,et al.  Peginterferon plus adefovir versus either drug alone for hepatitis delta. , 2011, The New England journal of medicine.

[45]  T. Asselah,et al.  Hepatitis B surface antigen serum level is associated with fibrosis severity in treatment-naïve, e antigen-positive patients. , 2013, Journal of hepatology.

[46]  Q. Ning,et al.  Sustained Immune Control in HBeAg-Positive Patients who Switched from Entecavir Therapy to Pegylated Interferon-α2a: 1 Year follow-up of the OSST Study , 2016, Antiviral therapy.

[47]  M. Buti,et al.  O117 : Predictors of clinical response: Results from a large, randomized controlled study with tenofovir disoproxil fumarate (TDF) plus peginterferon alfa-2A (PEG) combination for chronic hepatitis B (CHB) , 2015 .

[48]  M. Buti,et al.  Tenofovir discontinuation after long-term viral suppression in HBeAg negative chronic hepatitis B. Can HBsAg levels be useful? , 2015, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[49]  C. Boucher,et al.  Kinetics of hepatitis B surface antigen differ between treatment with peginterferon and entecavir. , 2011, Journal of hepatology.

[50]  F. Zoulim,et al.  Quantification of HBsAg in nucleos(t)ide-naïve patients treated for chronic hepatitis B with entecavir with or without tenofovir in the BE-LOW study. , 2015, Journal of hepatology.

[51]  M. Yuen,et al.  Hepatitis B surface antigen levels after hepatitis B e‐antigen seroclearance: a longitudinal follow‐up study , 2015, Liver international : official journal of the International Association for the Study of the Liver.

[52]  Y. Liaw,et al.  Systematic review: cessation of long‐term nucleos(t)ide analogue therapy in patients with hepatitis B e antigen‐negative chronic hepatitis B , 2015, Alimentary pharmacology & therapeutics.

[53]  D. Harnois.  Peginterferon plus Adefovir versus Either Drug Alone for Hepatitis Delta , 2011 .

[54]  I. Hung,et al.  High Hepatitis B Surface Antigen Levels Predict Insignificant Fibrosis in Hepatitis B e Antigen Positive Chronic Hepatitis B , 2012, PloS one.

[55]  A. Boonstra,et al.  Serum levels of interferon-gamma-inducible protein 10 and response to peginterferon therapy in HBeAg-positive chronic hepatitis B. , 2013, Journal of hepatology.

[56]  G. Bakalos,et al.  On‐treatment prediction of sustained response to peginterferon alfa‐2a for HBeAg‐negative chronic hepatitis B patients , 2015, Liver international : official journal of the International Association for the Study of the Liver.

[57]  R. Kaiser,et al.  The detection of HBsAg mutants expressed in vitro using two different quantitative HBsAg assays. , 2012, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[58]  N. Warner,et al.  The antiviral drug selected hepatitis B virus rtA181T/sW172* mutant has a dominant negative secretion defect and alters the typical profile of viral rebound , 2008, Hepatology.

[59]  J. Koskinas,et al.  Quantitative Analysis of Hepatitis D Virus RNA and Hepatitis B Surface Antigen Serum Levels in Chronic Delta Hepatitis Improves Treatment Monitoring , 2006, Antiviral therapy.

[60]  M. Manns,et al.  Hepatitis B Surface Antigen Concentrations in Patients with HIV/HBV Co-Infection , 2012, PloS one.

[61]  H. Wedemeyer,et al.  Dominance of hepatitis C virus (HCV) is associated with lower quantitative hepatitis B surface antigen and higher serum interferon-γ-induced protein 10 levels in HBV/HCV-coinfected patients. , 2015, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[62]  Olga Angelopoulou,et al.  Prediction of Treatment-Related HBsAg Loss in HBeAg-Negative Chronic Hepatitis B: A Clue from Serum HBsAg Levels , 2007, Antiviral therapy.

[63]  P. Schirmacher,et al.  Peginterferon alpha‐2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B , 2006, Hepatology.

[64]  H. Janssen,et al.  Nucleos(t)ide analogues only induce temporary hepatitis B e antigen seroconversion in most patients with chronic hepatitis B. , 2010, Gastroenterology.

[65]  D. Ouzan,et al.  Optimized HBsAg titer monitoring improves interferon therapy in patients with chronic hepatitis delta. , 2013, Journal of hepatology.

[66]  P. Marcellin,et al.  Hepatitis B surface antigen quantification: why and how to use it in 2011 - a core group report. , 2011, Journal of hepatology.

[67]  M. Rizzetto,et al.  Quantification of hepatitis B surface antigen with the novel DiaSorin LIAISON XL Murex HBsAg Quant: correlation with the ARCHITECT quantitative assays. , 2014, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[68]  M. Heikenwalder,et al.  Interferon-γ and Tumor Necrosis Factor-α Produced by T Cells Reduce the HBV Persistence Form, cccDNA, Without Cytolysis. , 2016, Gastroenterology.

[69]  F. Zoulim,et al.  Global strategies are required to cure and eliminate HBV infection , 2016, Nature Reviews Gastroenterology and Hepatology.

[70]  P. Marcellin,et al.  Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a. , 2009, Gastroenterology.

[71]  M. Brunetto,et al.  Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study. , 2002, Journal of hepatology.

[72]  P. Lampertico,et al.  Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negative patients treated with peginterferon alfa-2a. , 2012, Journal of hepatology.

[73]  P. Pontisso,et al.  Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus–coinfected patients , 2006, Hepatology.

[74]  P. Marcellin,et al.  Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients , 2012, Hepatology International.

[75]  W. Gerlich,et al.  Large surface proteins of hepatitis B virus containing the pre-s sequence , 1984, Journal of virology.

[76]  M. Manns,et al.  Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: a European perspective. , 2010, Journal of hepatology.

[77]  H. Tillmann,et al.  Virological and clinical characteristics of delta hepatitis in Central Europe , 2009, Journal of viral hepatitis.

[78]  F. Ikeda,et al.  Reactivation of hepatitis B virus during interferon‐free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co‐infection , 2016, Hepatology research : the official journal of the Japan Society of Hepatology.

[79]  P. Marcellin,et al.  Response to peginterferon alfa-2a (40KD) in HBeAg-negative CHB: on-treatment kinetics of HBsAg serum levels vary by HBV genotype. , 2013, Journal of hepatology.

[80]  C. Seeger,et al.  Molecular biology of hepatitis B virus infection. , 2015, Virology.

[81]  M. Manns,et al.  HBeAg‐positive hepatitis delta: virological patterns and clinical long‐term outcome , 2012, Liver international : official journal of the International Association for the Study of the Liver.

[82]  C. Yeh,et al.  Comparison of the elecsys HBsAg II assay and the architect assay for quantification of hepatitis B surface antigen in chronic hepatitis B patients , 2015, Biomedical journal.

[83]  K. Simon,et al.  Loss of intrahepatic HBsAg expression predicts sustained response to peginterferon and is reflected by pronounced serum HBsAg decline , 2014, Journal of viral hepatitis.

[84]  Ding-Shinn Chen,et al.  High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. , 2012, Gastroenterology.

[85]  V. Wong,et al.  Combination therapy of interferon and nucleotide/nucleoside analogues for chronic hepatitis B , 2014, Journal of viral hepatitis.

[86]  W. Gerlich.  Medical Virology of Hepatitis B: how it began and where we are now , 2013, Virology Journal.

[87]  G. Wong,et al.  Serum HBsAg quantification to predict response to peginterferon therapy of e antigen positive chronic hepatitis B , 2010, Alimentary pharmacology & therapeutics.

[88]  J. Summers,et al.  Coordinate regulation of replication and virus assembly by the large envelope protein of an avian hepadnavirus , 1994, Journal of virology.

[89]  Q. Ning,et al.  Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). , 2014, Journal of hepatology.

[90]  P. Marcellin,et al.  69 NEPTUNE STUDY: ON-TREATMENT HBSAG LEVEL ANALYSIS CONFIRMS PREDICTION OF RESPONSE OBSERVED IN PHASE 3 STUDY OF PEGINTERFERON ALFA-2A IN HBEAG-POSITIVE PATIENTS , 2011 .

[91]  K. Simon,et al.  Durable Hepatitis B Surface Antigen Decline in Hepatitis B E Antigen-Positive Chronic Hepatitis B Patients Treated with Pegylated Interferon-α2B: Relation to Response and HBV Genotype , 2012, Antiviral therapy.

[92]  M. Manns,et al.  Improved immune status corresponds with long-term decline of quantitative serum hepatitis B surface antigen in HBV/HIV co-infected patients. , 2012, Viral immunology.

[93]  M. Buti,et al.  Combination of Tenofovir Disoproxil Fumarate and Peginterferon α-2a Increases Loss of Hepatitis B Surface Antigen in Patients With Chronic Hepatitis B. , 2016, Gastroenterology.

[94]  J. Summers,et al.  Illegitimate replication of linear hepadnavirus DNA through nonhomologous recombination , 1995, Journal of virology.

[95]  M. Manns,et al.  Kinetics of hepatitis B surface antigen decline during 3 years of telbivudine treatment in hepatitis B e antigen–positive patients , 2010, Hepatology.

[96]  M. Manns,et al.  Hepatitis B Surface Antigen (Hbsag) Decrease and Serum Interferon-Inducible Protein-10 Levels as Predictive Markers for Hbsag Loss during Treatment with Nucleoside/Nucleotide Analogues , 2011, Antiviral therapy.

[97]  M. Manns,et al.  Late HDV RNA relapse after peginterferon alpha‐based therapy of chronic hepatitis delta , 2014, Hepatology.

[98]  K. Simon,et al.  Early on‐treatment prediction of response to peginterferon alfa‐2a for HBeAg‐negative chronic hepatitis B using HBsAg and HBV DNA levels , 2010, Hepatology.

[99]  Hehan Tang,et al.  O116 : Predictive value of baseline and on-treatment qHBsAg level in HBeAg positive CHB patients who switched from NUCs to pegylated interferon A-2A: A further analysis from new switch study , 2015 .

[100]  K. Simon,et al.  Long-term follow-up of hepatitis B e antigen-negative patients treated with peginterferon &agr;-2a: progressive decrease in hepatitis B surface antigen in responders , 2012, European journal of gastroenterology & hepatology.

[101]  S. Locarnini,et al.  Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: a perspective on Asia. , 2010, Journal of hepatology.

[102]  V. Wong,et al.  Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[103]  Chien-Jen Chen,et al.  A predictive scoring system for the seroclearance of HBsAg in HBeAg-seronegative chronic hepatitis B patients with genotype B or C infection. , 2013, Journal of hepatology.

[104]  P. Marcellin,et al.  917 ON-TREATMENT MONITORING OF HBsAg LEVELS TO PREDICT RESPONSE TO PEGINTERFERON ALFA-2A IN PATIENTS WITH HBeAg-POSITIVE CHRONIC HEPATITIS B , 2009 .

[105]  D. Tiniakos,et al.  Hepatitis B surface antigen: relation to hepatitis B replication parameters in HBeAg-negative chronic hepatitis B. , 2011, Journal of hepatology.

[106]  M. Cornberg,et al.  HBsAg seroclearance with NUCs: rare but important , 2014, Gut.

[107]  Xia-qiu Zhou,et al.  On-treatment serum HBsAg level is predictive of sustained off-treatment virologic response to telbivudine in HBeAg-positive chronic hepatitis B patients. , 2010, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[108]  P. Marcellin,et al.  Repeated Measurements of Hepatitis B Surface Antigen Identify Carriers of Inactive HBV During Long-term Follow-up. , 2016, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[109]  V. Dixit,et al.  HBsAg Level as Predictor of Liver Fibrosis in HBeAg Positive Patients With Chronic Hepatitis B Virus Infection. , 2015, Journal of clinical and experimental hepatology.

[110]  A. Georgiou,et al.  Serum HBsAg kinetics and usefulness of interferon‐inducible protein 10 serum in HBeAg‐negative chronic hepatitis B patients treated with tenofovir disoproxil fumarate , 2015, Journal of viral hepatitis.

[111]  V. Wong,et al.  Virological Response to Different Combination Regimes of Peginterferon α-2b and Lamivudine in Hepatitis B e Antigen Positive Chronic Hepatitis B , 2007, Antiviral therapy.

[112]  A. Rieger,et al.  Viral determinants predicting hepatitis B surface antigen (HBsAg) seroclearance in HIV‐/HBV‐coinfected patients , 2014, Journal of viral hepatitis.

[113]  Wenhui Li,et al.  Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus , 2012, eLife.

[114]  H. Zentgraf,et al.  Hepatitis B virus genome is organized into nucleosomes in the nucleus of the infected cell , 1994, Virus Genes.

[115]  J. Pawlotsky,et al.  Long-term hepatitis B surface antigen (HBsAg) kinetics during nucleoside/nucleotide analogue therapy: finite treatment duration unlikely. , 2013, Journal of hepatology.

[116]  C. Gibbs,et al.  Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. , 2004, Gastroenterology.

[117]  F. Zoulim,et al.  New antiviral targets for innovative treatment concepts for hepatitis B virus and hepatitis delta virus. , 2016, Journal of hepatology.

[118]  G. Zang,et al.  Serum hepatitis B surface antigen quantification as a useful assessment for significant fibrosis in hepatitis B e antigen‐positive hepatitis B virus carriers , 2013, Journal of gastroenterology and hepatology.

[119]  S. Lewin,et al.  Serum hepatitis B surface antigen and hepatitis B e antigen titers: Disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers , 2010, Hepatology.

[120]  I. Hung,et al.  Patterns of hepatitis B surface antigen decline and HBV DNA suppression in Asian treatment-experienced chronic hepatitis B patients after three years of tenofovir treatment. , 2013, Journal of hepatology.

[121]  M. Manns,et al.  Correlation between the Elecsys HBsAg II assay and the Architect assay for the quantification of hepatitis B surface antigen (HBsAg) in the serum. , 2011, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[122]  C. Boucher,et al.  Prediction of sustained response to peginterferon alfa‐2b for hepatitis B e antigen–positive chronic hepatitis B using on‐treatment hepatitis B surface antigen decline , 2010, Hepatology.

[123]  K. Simon,et al.  Presence of precore and core promoter mutants limits the probability of response to peginterferon in hepatitis B e antigen‐positive chronic hepatitis B , 2012, Hepatology.