title: Long-term therapy of chronic delta hepatitis with peginterferon alfa.
abstract: BACKGROUND
  Chronic delta hepatitis virus (HDV) infection rapidly progresses to cirrhosis. Treatment with peginterferon for up to 2 years is often without durable response.
  
  
  OBJECTIVE
  To examine the efficacy and safety of long-term peginterferon in achieving a durable response.
  
  
  METHODS
  Treatment was initiated with 180 μg/week of peginterferon alfa-2a with titration to a maximal tolerable dose, for up to 5 years. Liver biopsies and hepatic venous pressure gradients (HVPG) were evaluated at baseline, 1, 3 and 5 years. The primary endpoint was histological improvement or loss of serum HDV and HBsAg at 3 years.
  
  
  RESULTS
  Thirteen patients were treated for a median of 140 weeks (6-260) with an average peginterferon dose of 180 μg/week (90-270). At baseline, most had advanced disease (median Ishak fibrosis = 3) with portal hypertension (HVPG = 10.2 ± 6 mmHg). Five of 13 patients (39%) achieved the primary endpoint, with three seroconverting for HBsAg after 24, 37 and 202 weeks of treatment. Histological inflammation improved after 1 year, (median HAI: 10 vs. 7, P = 0.01) with persistence in 4/5 patients at 3 years (median HAI: 7.5). Greatest improvements occurred in the first year. Baseline bilirubin and HBsAg levels were significantly lower in virological responders than nonresponders. After 12 weeks, virological responders had a significant decline in HBsAg (1.5 log10 IU/mL, P = 0.05).
  
  
  CONCLUSIONS
  Despite increased doses and duration of therapy, treatment of chronic HDV with peginterferon remains unsatisfactory. Quantitative measures of HBsAg may be an important biomarker of early response to peginterferon therapy in chronic delta hepatitis virus infection.
authors.affiliation: Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Heller
authors.forename: Y
authors.initials: Y
authors.lastname: Rotman
authors.forename: C
authors.initials: C
authors.lastname: Koh
authors.forename: S
authors.initials: S
authors.lastname: Clark
authors.forename: V
authors.initials: V
authors.lastname: Haynes-Williams
authors.forename: R
authors.initials: R
authors.lastname: Chang
authors.forename: R
authors.initials: R
authors.lastname: McBurney
authors.forename: P
authors.initials: P
authors.lastname: Schmid
authors.forename: J
authors.initials: J
authors.lastname: Albrecht
authors.forename: D E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: M G
authors.initials: MG
authors.lastname: Ghany
authors.forename: T J
authors.initials: TJ
authors.lastname: Liang
authors.forename: J H
authors.initials: JH
authors.lastname: Hoofnagle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D019701:Hepatitis D, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000209:etiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a