title: Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta.
abstract: Interferon alpha is the only treatment option for hepatitis delta virus (HDV). Trials investigating the efficacy of pegylated interferon alpha (PEG-IFNa) showed HDV RNA negativity rates of 25-30% 24 weeks after therapy. However, the clinical and virological long-term outcome of HDV-infected patients treated with PEG-IFNa is unknown. We performed a retrospective-prospective follow-up of 77 patients treated for 48 weeks with either PEG-alfa-2a and adefovir (ADV) or either drug alone in the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-1) trial. Long-term follow-up data were available for 58 out of 77 patients (75%) with a median time of follow-up of 4.5 (0.5-5.5) years and a median 3 visits per patient. Patients treated with ADV alone received retreatment with PEG-IFNa (48% versus 19%; P = 0.02) more often. Hepatitis B virus surface antigen (HBsAg) became negative in six PEG-IFNa-treated patients until the end of long-term follow-up (10%). Sixteen patients tested HDV RNA-negative 6 months after PEG-IFNa treatment who were entered in the long-term follow-up study. Out of these, nine individuals tested HDV RNA-positive at least once during further long-term follow-up, with seven patients being HDV RNA-positive at the most recent visit. Clinical endpoints (liver-related death, liver transplantation, hepatic decompensation, hepatocellular carcinoma) were observed in three PEG-IFNa-treated (8%) and three ADV-treated (14%) patients during posttreatment long-term follow-up with an overall annual event rate of 2.5% (4.9% in cirrhosis). Sequencing confirmed the reappearance of pretreatment virus strains in all cases.
  
  
  CONCLUSIONS
  Late HDV RNA relapses may occur after PEG-IFNa therapy of hepatitis delta and thus the term sustained virological response should be avoided in HDV infection. The annual posttreatment rate of clinical events in hepatitis delta patients eligible for PEG-IFNa therapy is about 2.5% and 4.9% in patients with cirrhosis.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), partner site, Hannover-Braunschweig, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Heidrich
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydın
authors.forename: Gökhan
authors.initials: G
authors.lastname: Kabaçam
authors.forename: Boris A
authors.initials: BA
authors.lastname: Ratsch
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Zachou
authors.forename: Birgit
authors.initials: B
authors.lastname: Bremer
authors.forename: George N
authors.initials: GN
authors.lastname: Dalekos
authors.forename: Andreas
authors.initials: A
authors.lastname: Erhardt
authors.forename: Fehmi
authors.initials: F
authors.lastname: Tabak
authors.forename: Kendal
authors.initials: K
authors.lastname: Yalcin
authors.forename: Selim
authors.initials: S
authors.lastname: Gürel
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.forename: C-Thomas
authors.initials: CT
authors.lastname: Bock
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D019701:Hepatitis D, Chronic / Q000188:drug therapy* / Q000401:mortality / Q000821:virology*; D003698:Hepatitis Delta Virus / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a