Kinetics of Hepatitis B Surface Antigen Level in Chronic Hepatitis B Patients who Achieved Hepatitis B Surface Antigen Loss during Pegylated Interferon Alpha-2a Treatment

Background: Hepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B (CHB). This study aimed to assess the patterns of HBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon (PEG-IFN) &agr;-2a. Methods: A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen (HBeAg)-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN &agr;-2a180 &mgr;g/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during PEG-IFN &agr;-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1–3 months. Results: Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3% and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72–96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients (2.9 ± 1.1 log IU/ml) compared with HBeAg-negative patients (2.0 ± 1.3 log IU/ml; t = 4.733, P < 0.001), but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss. Conclusions: Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss.

[1]  W. Alexander,et al.  European Association for the Study of the Liver , 1968 .

[2]  A. Lok,et al.  Interferon Treatment for Hepatitis B. , 2016, Clinics in liver disease.

[3]  H. Nomura,et al.  Long‐term follow up of peginterferon‐α‐2a treatment of hepatitis B e‐antigen (HBeAg) positive and HBeAg negative chronic hepatitis B patients in phase II and III studies , 2016, Hepatology research : the official journal of the Japan Society of Hepatology.

[4]  Jun Cheng,et al.  Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a. , 2016, World journal of hepatology.

[5]  Xiaoyuan Xu,et al.  Dynamic Characteristics of Serum Hepatitis B Surface Antigen in Chinese Chronic Hepatitis B Patients Receiving 7 Years of Entecavir Therapy , 2016, Chinese medical journal.

[6]  H. Yim,et al.  A Decade-old Change in the Screening Rate for Hepatocellular Carcinoma Among a Hepatitis B Virus-infected Population in Korea , 2016, Chinese medical journal.

[7]  Yoshiyuki Suzuki,et al.  Long-term effects of peginterferon alfa-2a therapy in Japanese patients with chronic hepatitis B virus infection , 2015, Virology Journal.

[8]  Ming‐Lung Yu,et al.  Pegylated-Interferon Alpha Therapy for Treatment-Experienced Chronic Hepatitis B Patients , 2015, PLoS ONE.

[9]  F. Zoulim,et al.  Antiviral therapies and prospects for a cure of chronic hepatitis B. , 2015, Cold Spring Harbor perspectives in medicine.

[10]  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.

[11]  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.

[12]  Maggie Westby,et al.  Diagnosis and management of chronic hepatitis B in children, young people, and adults: summary of NICE guidance , 2013, BMJ.

[13]  H. Janssen,et al.  Close Monitoring of Hepatitis B Surface Antigen Levels Helps Classify Flares During Peginterferon Therapy and Predicts Treatment Response , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  Q. Mao,et al.  Efficacy of pegylated interferon α2a in patients without HBeAg loss after the withdrawal of long-term lamivudine therapy , 2013, Virology Journal.

[15]  P. Lampertico,et al.  Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B , 2012, Gut.

[16]  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.

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

[18]  P. Marcellin,et al.  Hepatitis B surface antigen: association with sustained response to peginterferon alfa-2a in hepatitis B e antigen-positive patients , 2013, Hepatology International.

[19]  F. Sanai,et al.  Efficacy of peginterferon α-2a and predictors of response in HBeAg-negative, genotype D-naive patients , 2011, Hepatology International.

[20]  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.

[21]  F. Liu,et al.  [High rates of HBsAg loss and seroconversion result from prolonged course of pegasys treatment]. , 2011, Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology.

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

[23]  Lai Wei,et al.  Quantitative serum HBsAg and HBeAg are strong predictors of sustained HBeAg seroconversion to pegylated interferon alfa‐2b in HBeAg‐positive patients , 2010, Journal of gastroenterology and hepatology.

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

[25]  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.

[26]  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.

[27]  M. Brunetto.  A new role for an old marker, HBsAg. , 2010, Journal of hepatology.

[28]  C. Chu,et al.  Hepatitis B surface antigen seroclearance during chronic HBV infection , 2010, Antiviral therapy.

[29]  T. Asselah,et al.  Early serum HBsAg drop: A strong predictor of sustained virological response to pegylated interferon alfa‐2a in HBeAg‐negative patients , 2009, Hepatology.

[30]  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.

[31]  K. Simon,et al.  Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b. , 2008, Gastroenterology.

[32]  R. Gish,et al.  A Pilot Study of Extended Duration Peginterferon Alfa-2a for Patients With Hepatitis B e Antigen-Negative Chronic Hepatitis B , 2007, The American Journal of Gastroenterology.

[33]  G. Fattovich,et al.  Long-term outcome of chronic hepatitis B in Caucasian patients: mortality after 25 years , 2007, Gut.

[34]  C. Chu,et al.  Spontaneous relapse of hepatitis in inactive HBsAg carriers , 2007, Hepatology international.

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

[36]  A. Schattner,et al.  Interferon treatment for hepatitis. , 1989, Israel journal of medical sciences.