Treatment of Patients with Chronic Hepatitis B who have Failed Previous Antiviral Treatment with Pegylated Interferon α2a (40 kDa; PEGASYS®)

Background Although nucleot(s)ide analogues can effectively suppress hepatitis B virus (HBV) replication, many patients experience relapse of hepatitis after cessation of treatment. We aimed to investigate the efficacy of pegylated interferon α2a (PEG-IFN-α2a) in these difficult-to-treat patients. Methods Chronic hepatitis B patients who have received antiviral drugs for ≥12 months and stopped for ≥6 months were treated by 48-week PEG-IFN-α2a. Virological response was defined as HBV DNA <10,000 copies/ml and hepatitis B e antigen (HBeAg) seroconversion (for HBeAg-positive patients). Results A total of 40 patients, 29 HBeAg-positive and 11 HBeAg-negative, with median log10 HBV DNA 7.3 copies/ml and alanine aminotransferase 110 IU/ml were studied. The last antiviral treatment was given for 92 +61 weeks and stopped for 176 +88 weeks. At the end of treatment, 22 (12 HBeAg-positive and 10 HBeAg-negative; 55%) patients had virological response and 16 (7 HBeAg-positive and 9 HBeAg-negative; 40%) patients had undetectable HBV DNA (<100 copies/ml). At 24 weeks post-treatment, 14 (8 HBeAg-positive and 6 HBeAg-negative; 35%) patients had virological response and 9 (5 HBeAg-positive and 4 HBeAg-negative; 23%) patients had undetectable HBV DNA. Two (5%) patients had lost hepatitis B surface antigen. HBV DNA levels at week 24 best predicted sustained virological response (area under curve 0.76, 95% confidence interval 0.60–0.92, P=0.007). At HBV DNA cutoffs of 3 logs and 5 logs at week 24, the sensitivity/specificity for sustained virological response were 50%/85% and 86%/62%, respectively. Conclusions PEG-IFN-α2a was effective in the treatment of chronic hepatitis B patients who have failed previous antiviral treatment.

[1]  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.

[2]  V. Wong,et al.  High viral load and hepatitis B virus subgenotype ce are associated with increased risk of hepatocellular carcinoma. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  V. Wong,et al.  High viral load and hepatitis B virus subgenotype ce are associated with increased risk of hepatocellular carcinoma. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  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.

[5]  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.

[6]  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.

[7]  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.

[8]  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.

[9]  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.

[10]  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.

[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]  Hao Wang,et al.  Two-year Lamivudine treatment for Hepatitis B e Antigen-Negative Chronic Hepatitis B: A Double-Blind, Placebo-Controlled Trial , 2006, Antiviral therapy.

[13]  Hao Wang,et al.  Two-year Lamivudine treatment for Hepatitis B e Antigen-Negative Chronic Hepatitis B: A Double-Blind, Placebo-Controlled Trial , 2006, Antiviral therapy.

[14]  P. Loehrer,et al.  Risk of Hepatocellular Carcinoma Across a Biological Gradient of Serum Hepatitis B Virus DNA Level , 2007 .

[15]  P. Loehrer,et al.  Risk of Hepatocellular Carcinoma Across a Biological Gradient of Serum Hepatitis B Virus DNA Level , 2007 .

[16]  H. Janssen,et al.  Successful Treatment with Peginterferon alfa-2b of HBeAg-positive HBV Non-Responders to Standard Interferon or Lamivudine , 2006, The American Journal of Gastroenterology.

[17]  H. Janssen,et al.  Successful Treatment with Peginterferon alfa-2b of HBeAg-positive HBV Non-Responders to Standard Interferon or Lamivudine , 2006, The American Journal of Gastroenterology.

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

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

[20]  E. Schiff,et al.  A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. , 2006, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[21]  E. Schiff,et al.  A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. , 2006, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[22]  A. Lok,et al.  Sensitive Line Probe Assay That Simultaneously Detects Mutations Conveying Resistance to Lamivudine and Adefovir , 2006, Journal of Clinical Microbiology.

[23]  A. Lok,et al.  Sensitive Line Probe Assay That Simultaneously Detects Mutations Conveying Resistance to Lamivudine and Adefovir , 2006, Journal of Clinical Microbiology.

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

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

[26]  V. Wong,et al.  Long-Term Lamivudine Treatment is Associated with a Good Maintained Response in Severe Acute Exacerbation of Chronic Hbeag-Negative Hepatitis B , 2005, Antiviral therapy.

[27]  V. Wong,et al.  Long-Term Lamivudine Treatment is Associated with a Good Maintained Response in Severe Acute Exacerbation of Chronic Hbeag-Negative Hepatitis B , 2005, Antiviral therapy.

[28]  H. Chan,et al.  Systematic review: treatment of chronic hepatitis B virus infection by pegylated interferon , 2005, Alimentary pharmacology & therapeutics.

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

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

[31]  Y. Liaw,et al.  Asian‐Pacific consensus statement on the management of chronic hepatitis B: a 2005 update , 2005, Liver international : official journal of the International Association for the Study of the Liver.

[32]  Y. Liaw,et al.  Asian‐Pacific consensus statement on the management of chronic hepatitis B: a 2005 update , 2005, Liver international : official journal of the International Association for the Study of the Liver.

[33]  V. Wong,et al.  Long‐term follow‐up of peginterferon and lamivudine combination treatment in HBeAg‐positive chronic hepatitis B , 2005, Hepatology.

[34]  V. Wong,et al.  Long‐term follow‐up of peginterferon and lamivudine combination treatment in HBeAg‐positive chronic hepatitis B , 2005, Hepatology.

[35]  V. Wong,et al.  Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy. , 2005, Gastroenterology.

[36]  V. Wong,et al.  Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy. , 2005, Gastroenterology.

[37]  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.

[38]  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.

[39]  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.

[40]  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.

[41]  Y. Liaw,et al.  Maximal early HBV suppression is predictive of optimal virologic and clinical efficacy in nucleoside-treated hepatitis B patients: scientific observations from a large multinational trial (the GLOBE study) , 2005 .

[42]  Y. Liaw,et al.  Maximal early HBV suppression is predictive of optimal virologic and clinical efficacy in nucleoside-treated hepatitis B patients: scientific observations from a large multinational trial (the GLOBE study) , 2005 .

[43]  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.

[44]  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.

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

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

[47]  R. D. de Man,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 , 2003, Gut.

[48]  R. D. de Man,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 , 2003, Gut.

[49]  G. Davis Monitoring of viral levels during therapy of hepatitis C , 2002, Hepatology.

[50]  G. Davis Monitoring of viral levels during therapy of hepatitis C , 2002, Hepatology.

[51]  W. Lau,et al.  Factors associated with viral breakthrough in lamivudine monoprophylaxis of hepatitis B virus recurrence after liver transplantation , 2002, Journal of medical virology.

[52]  W. Lau,et al.  Factors associated with viral breakthrough in lamivudine monoprophylaxis of hepatitis B virus recurrence after liver transplantation , 2002, Journal of medical virology.

[53]  H. Kim,et al.  Effect of virological response on post‐treatment durability of lamivudine‐induced HBeAg seroconversion , 2002, Journal of viral hepatitis.

[54]  H. Kim,et al.  Effect of virological response on post‐treatment durability of lamivudine‐induced HBeAg seroconversion , 2002, Journal of viral hepatitis.

[55]  J. Sung,et al.  Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection , 2002, American Journal of Gastroenterology.

[56]  J. Sung,et al.  Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection , 2002, American Journal of Gastroenterology.

[57]  B. McMahon,et al.  Chronic hepatitis B , 2001, Hepatology.

[58]  S. Nair,et al.  Serum alanine aminotransferase flares during interferon treatment of chronic hepatitis B: Is sustained clearance of HBV DNA dependent on levels of pretreatment viremia? , 2001, Hepatology.

[59]  S. Nair,et al.  Serum alanine aminotransferase flares during interferon treatment of chronic hepatitis B: Is sustained clearance of HBV DNA dependent on levels of pretreatment viremia? , 2001, Hepatology.

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

[61]  H. Lee,et al.  Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea , 2000, Hepatology.

[62]  H. Lee,et al.  Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea , 2000, Hepatology.

[63]  K. Loeb,et al.  High‐Throughput Quantitative Analysis of Hepatitis B Virus DNA in Serum Using the TaqMan Fluorogenic Detection System , 2000, Hepatology.

[64]  K. Loeb,et al.  High‐Throughput Quantitative Analysis of Hepatitis B Virus DNA in Serum Using the TaqMan Fluorogenic Detection System , 2000, Hepatology.

[65]  P. Rosenthal,et al.  American Association for the Study of Liver Diseases , 1993, IDrugs : the investigational drugs journal.

[66]  P. Rosenthal,et al.  American Association for the Study of Liver Diseases , 1993, IDrugs : the investigational drugs journal.

[67]  M Lindh,et al.  Genotypes, nt 1858 variants, and geographic origin of hepatitis B virus--large-scale analysis using a new genotyping method. , 1997, The Journal of infectious diseases.

[68]  M Lindh,et al.  Genotypes, nt 1858 variants, and geographic origin of hepatitis B virus--large-scale analysis using a new genotyping method. , 1997, The Journal of infectious diseases.