title: Association Between Level of Hepatitis D Virus RNA at Week 24 of Pegylated Interferon Therapy and Outcome.
abstract: OBJECTIVE
  Interferon is the only effective treatment for chronic hepatitis D virus (HDV) infection. No rules have been set for stopping treatment based on viral kinetics. We analyzed data from an international study of hepatitis D treatment to identify factors associated with outcomes of pegylated interferon treatment, with and without adefovir.
  
  
  METHODS
  We analyzed data from the Hep-Net-International Delta Hepatitis Intervention Trial on 50 patients with compensated liver disease who tested positive for anti-HDV and HDV RNA. Subjects received pegylated interferon α 2a, with adefovir or placebo, or only adefovir, for 48 weeks. Twenty-four weeks after treatment ended, 41 patients were evaluated for levels of HDV RNA and DNA, liver enzymes, and hepatitis B surface antigen (HBsAg); liver biopsy specimens were analyzed for fibrosis. Response to therapy was defined as end-of-treatment response or post-treatment week 24 virologic response. In both cases virologic response was associated with undetectable HDV RNA levels. Patients with less than a 1 log decrease in HDV RNA at the end of treatment were considered null responders.
  
  
  RESULTS
  Based on univariate and multivariate analysis, the level of HDV RNA at week 24 of treatment was associated more strongly with response to therapy than other factors analyzed. The level of HBsAg at week 24 of treatment was associated with a response to therapy only in univariate analysis. Lack of HDV RNA at week 24 of treatment, or end of treatment, identified responders with positive predicted values of 71% and 100%, respectively. At 24 weeks after treatment, a decrease in HDV RNA level of less than 1 log, combined with no decrease in HBsAg level, identified null responders with a positive predictive value of 83%. A decrease in HDV RNA level of more than 2 log at week 24 of treatment identified null responders with a negative predictive value of 95%.
  
  
  CONCLUSIONS
  Based on an analysis of data from a large clinical trial, the level of HDV RNA at week 24 of treatment with pegylated interferon, with or without adefovir for 48 weeks, can identify patients who will test negative for HDV RNA 24 weeks after the end of treatment. This information can be used to help physicians manage patients receiving therapy for chronic hepatitis D.
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Onur
authors.initials: O
authors.lastname: Keskin
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Tüzün
authors.affiliation: Department of Internal Medicine, Academic Liver Unit and Research Labarotory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Zachou
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Xheni
authors.initials: X
authors.lastname: Deda
authors.affiliation: Department of Internal Medicine, Academic Liver Unit and Research Labarotory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece.
authors.forename: George N
authors.initials: GN
authors.lastname: Dalekos
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Heidrich
authors.affiliation: Department of Biostatistics, University of Yildirim Beyazit Medical School, Ankara, Turkey.
authors.forename: Selcen
authors.initials: S
authors.lastname: Pehlivan
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Frankfurt Medical School, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Department of Gastroenterology, Dicle University, Diyarbakir, Turkey.
authors.forename: Kendal
authors.initials: K
authors.lastname: Yalçın
authors.affiliation: Department of Gastroenterology, Uludağ University, Bursa, Turkey.
authors.forename: Selim
authors.initials: S
authors.lastname: Gürel
authors.affiliation: Department of Infectious Diseases, Cerrahpaşa Medical School, University of Istanbul, Istanbul, Turkey.
authors.forename: Fehmi
authors.initials: F
authors.lastname: Tabak
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Idilman
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Bozkaya
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Manns
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey; Hepatology Institute, University of Ankara, Ankara, Turkey. Electronic address: cihan.yurdaydin@medicine.ankara.edu.tr.
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydin
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood; D019701:Hepatitis D, Chronic / Q000188:drug therapy*; D003698:Hepatitis Delta Virus / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D010919:Placebos / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins / Q000627:therapeutic use; D000637:Transaminases / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D063065:Organophosphonates; D010919:Placebos; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C053001:adefovir; D000637:Transaminases; D000225:Adenine; C100416:peginterferon alfa-2a
keywords: Chronic Delta Hepatitis; On-Treatment HDV RNA; Pegylated Interferon Treatment; Treatment Outcome Prediction