title: Maintenance therapy with peginterferon alfa-2b does not prevent hepatocellular carcinoma in cirrhotic patients with chronic hepatitis C.
abstract: OBJECTIVE
  Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma (HCC) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC)3 program.
  
  
  METHODS
  Data were analyzed from an open-label randomized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin. All patients had compensated cirrhosis with no evidence of HCC. Patients received peginterferon alfa-2b (0.5 μg/kg/week; n=311) or no treatment (controls, n=315) for a maximum period of 5 years or until 98 patients had a clinical event (hepatic decompensation, HCC, death, or liver transplantation). The primary measure of efficacy was time until the first clinical event.
  
  
  RESULTS
  There was no significant difference in time to first clinical event among patients who received peginterferon alfa-2b compared with controls (hazard ratio [HR], 1.452; 95% confidence interval [CI]: 0.880-2.396). There was no decrease in the development of HCC with therapy. The time to disease progression (clinical events or new or enlarged varices) was significantly longer for patients who received peginterferon alfa-2b compared with controls (HR, 1.564; 95% CI: 1.130-2.166). In a prospectively defined subanalysis of patients with baseline portal hypertension, peginterferon alfa-2b significantly increased the time to first clinical event compared with controls (P=.016). There were no new safety observations.
  
  
  CONCLUSIONS
  Maintenance therapy with peginterferon alfa-2b is not warranted in all patients and does not prevent HCC. However, there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension.
authors.affiliation: BCLC Group, Liver Unit, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red de Hepatología y Enfermedades Digestivas, Barcelona, Spain. jbruix@clinic.ub.es
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruix
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.forename: Eugene
authors.initials: E
authors.lastname: Schiff
authors.forename: Kelly
authors.initials: K
authors.lastname: Burak
authors.forename: Elizabeth J L
authors.initials: EJ
authors.lastname: Heathcote
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Jorge-Luis
authors.initials: JL
authors.lastname: Poo
authors.forename: Carlos Brandao
authors.initials: CB
authors.lastname: Mello
authors.forename: Rainer
authors.initials: R
authors.lastname: Guenther
authors.forename: Claus
authors.initials: C
authors.lastname: Niederau
authors.forename: Ruben
authors.initials: R
authors.lastname: Terg
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.forename: Navdeep
authors.initials: N
authors.lastname: Boparai
authors.forename: Louis H
authors.initials: LH
authors.lastname: Griffel
authors.forename: Margaret
authors.initials: M
authors.lastname: Burroughs
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Brass
authors.forename: Janice K
authors.initials: JK
authors.lastname: Albrecht
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy / Q000821:virology; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D008113:Liver Neoplasms / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009656:North America; D018579:Patient Selection; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D018570:Risk Assessment; D012307:Risk Factors; D013020:South America; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b