title: Randomized clinical trial:  a pilot study investigating the safety and effectiveness of an escalating dose of peginterferon α-2a monotherapy for 48 weeks compared with standard clinical care in patients with hepatitis C cirrhosis.
abstract: BACKGROUND
  A substantial proportion of patients with chronic hepatitis C virus (HCV) cirrhosis fail to eradicate infection and develop liver-related complications. Despite evidence that interferon-α has an antifibrotic effect, clinical trials have demonstrated that low-dose maintenance interferon does not improve outcomes in patients with compensated HCV cirrhosis following a lead-in phase of interferon. In a pilot study, we have investigated the efficacy of an escalating dose of pegylated interferon α-2a (PEG-IFN2a) as compared with standard clinical care in patients with more advanced HCV Child's A or B cirrhosis without a lead-in phase.
  
  
  METHODS
  In a prospective study, 40 patients were randomized to receive either standard clinical care (no further antiviral therapy) or 48 weeks of treatment with PEG-IFN2a starting at 90 mcg and escalating to 180 mcg weekly if tolerated. Patients were thereafter followed for a mean duration of 41 months. The primary outcome variables were liver-related death, all-cause mortality and sustained virological response. The secondary outcomes were 'liver-related events' and health-related quality of life.
  
  
  RESULTS
  Both groups were well matched, with treatment well tolerated. The incidences of all-cause mortality (P=0.024) and nononcological liver morbidity (P=0.04) were significantly higher in the control arm after a mean of 47 months of follow-up.
  
  
  CONCLUSIONS
  A 48-week escalating dose of PEG-IFN2a is associated with a significant reduction in all-cause mortality and nononcological liver-related morbidity in this trial. Further investigation of PEG-IFN2a is warranted for patients with advanced HCV-related cirrhosis for whom there is no other treatment and where transplantation is associated with rapid progression to cirrhosis.
authors.affiliation: Department of Medicine, Centre for Hepatology, University College London, London, UK. sudeep.tanwar@nhs.net
authors.forename: Sudeep
authors.initials: S
authors.lastname: Tanwar
authors.forename: Mark
authors.initials: M
authors.lastname: Wright
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Ryder
authors.forename: Peter R
authors.initials: PR
authors.lastname: Mills
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Cramp
authors.forename: Julie
authors.initials: J
authors.lastname: Parkes
authors.forename: William M
authors.initials: WM
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D011788:Quality of Life; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a