title: Pegylated-interferon alpha therapy for treatment-experienced chronic hepatitis B patients.
abstract: BACKGROUND
  Studies are limited on pegylated interferon (Peg-IFN) therapy for chronic hepatitis B (CHB) patients who failed or relapsed on previous antiviral therapy.
  
  
  OBJECTIVE
  We aimed to investigate the effect of Peg-IFN therapy in treatment-experienced CHB patients.
  
  
  METHODS
  A total of 57 treatment-experienced CHB patients at two medical centers were enrolled. All of the patients were treated with Peg-IFN α-2a at 180 μg weekly for 24 or 48 weeks. The hepatitis B serological markers and viral loads were tested every 3 months until 1 year after stopping Peg-IFN therapy. The endpoints were HBV DNA <2000IU/mL, hepatitis B e antigen (HBeAg) seroconversion, and a hepatitis B surface antigen (HBsAg) loss at 12 months post-treatment.
  
  
  RESULTS
  In HBeAg-positive patients, 25.0%, 29.2%, and 12.5% of the patients achieved HBeAg seroconversion, HBV DNA <2000 IU/mL and a combined response, respectively, at 12 months post-treatment. Prior IFN therapy, a high baseline ALT level, a low creatinine level, undetectable HBV DNA at 12 weeks and a decline in HBV DNA >2 log10 IU/mL at 12 weeks of therapy were factors associated with treatment response. In HBeAg-negative patients, 9.1%, 15.2%, and 6.1% of the patients achieved undetectable HBV DNA, HBV DNA <2000 IU/mL, and an HBsAg loss, respectively, at 12 months post-treatment. No factor was significantly associated with the treatment response in the HBeAg-negative patients. The median HBsAg level declined from 3.4 to 2.6 log10 IU/mL in all the patients, and the 5-year cumulative rate of the HBsAg loss was 9.8% in the HBeAg-negative patients. Overall, none of the patients prematurely discontinued the Peg-IFN therapy.
  
  
  CONCLUSIONS
  Peg-IFN re-treatment is effective for a proportion of HBeAg-positive treatment-experienced patients; it has limited efficacy for HBeAg-negative treatment-experienced patients. Peg-IFN might facilitate HBsAg loss in HBeAg-negative treatment-experienced patients.
authors.affiliation: Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Lun
authors.initials: ML
authors.lastname: Yeh
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Peng
authors.affiliation: Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Hsueh-Chou
authors.initials: HC
authors.lastname: Lai
authors.affiliation: Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Departmentof Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Yen
authors.initials: MY
authors.lastname: Hsieh
authors.affiliation: Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Departmentof Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jee-Fu
authors.initials: JF
authors.lastname: Huang
authors.affiliation: Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shinn-Cherng
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
authors.affiliation: Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D004279:DNA, Viral / Q000037:antagonists & inhibitors* / Q000235:genetics; D004334:Drug Administration Schedule; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D003404:Creatinine; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a
references.citation: Hepatology. 2009 Apr;49(4):1151-7
references.pmid: 19115222
references.citation: J Gastroenterol Hepatol. 2011 Mar;26(3):456-60
references.pmid: 21332542
references.citation: J Hepatol. 2011 Nov;55(5):1121-31
references.pmid: 21718667
references.citation: J Gastroenterol Hepatol. 2010 Sep;25(9):1498-506
references.pmid: 20796146
references.citation: Hepatology. 2013 Nov;58(5):1537-47
references.pmid: 23389810
references.citation: Aliment Pharmacol Ther. 2012 Feb;35(4):458-68
references.pmid: 22225574
references.citation: J Hepatol. 2007 Jan;46(1):45-52
references.pmid: 17107734
references.citation: Hepatology. 2011 Nov;54(5):1591-9
references.pmid: 22045673
references.citation: Hepatology. 2013 Dec;58(6):1888-96
references.pmid: 23744454
references.citation: Hepatol Int. 2013 Mar;7(1):88-97
references.pmid: 23518903
references.citation: Hepatology. 2013 Jul;58(1):98-107
references.pmid: 23213040
references.citation: Aliment Pharmacol Ther. 2010 Dec;32(11-12):1323-31
references.pmid: 21050234
references.citation: J Hepatol. 2012 May;56(5):1006-11
references.pmid: 22245886
references.citation: Aliment Pharmacol Ther. 2013 Jul;38(2):98-106
references.pmid: 23713520
references.citation: N Engl J Med. 2008 Oct 2;359(14):1486-500
references.pmid: 18832247
references.citation: J Hepatol. 2013 Dec;59(6):1153-9
references.pmid: 23872601
references.citation: Hepatology. 2010 Oct;52(4):1251-7
references.pmid: 20830787
references.citation: Hepatol Int. 2013 Jun;7(2):429-36
references.pmid: 21701902
references.citation: Gastroenterology. 2010 Aug;139(2):491-8
references.pmid: 20381492
references.citation: N Engl J Med. 2006 Mar 9;354(10):1001-10
references.pmid: 16525137
references.citation: N Engl J Med. 2005 Jun 30;352(26):2682-95
references.pmid: 15987917
references.citation: N Engl J Med. 2004 Sep 16;351(12):1206-17
references.pmid: 15371578
references.citation: FEBS Lett. 1999 Apr 30;450(1-2):66-71
references.pmid: 10350059
references.citation: Hepatology. 2009 Apr;49(4):1141-50
references.pmid: 19338056