title: Deciding on Interferon-Free Treatment for Chronic Hepatitis C: Updating Liver Stiffness Cut-Off Values to Maximize Benefit.
abstract: BACKGROUND
  In a perspective of economic constraints the prioritizing of patients to IFN-free regimens is mainly based on the determination of liver stiffness by transient elastography (TE). Being a continuous variable the interpretation of TE results requires the identification of cut-off values, to date set to maximize diagnostic accuracy even if such values should be better based on more helpful outcome prediction endpoints.
  
  
  OBJECTIVE
  To define the TE cut-off values in different clinical scenarios, including new IFN-free regimens, and to balance the clinical benefits versus harms in treated and untreated patients.
  
  
  METHODS
  We assessed the accuracy of TE in staging 728 consecutive HCV patients and the distribution of TE values in 1,001 blood donors. Ten experts quantified the expected harm/benefit ratio for 6 scenarios resulting from 2 stages of liver disease (F≥2 or F≥3) and 3 treatment regimens: PEGIFN+ribavirin, PEGIFN+RBV+first-generation protease inhibitor, and IFN-free regimens. The optimal TE cut-off values were identified using the Metz equation.
  
  
  RESULTS
  The estimated mean expected harm/benefit ratio for IFN-free regimens was 1/8.3 in patients with F≥2 and 1/10 in those with F≥3. The resulting optimal cut-off values were respectively 4.5 kPa with sensitivity at 99% and specificity at 12%, and 6.8 kPa with sensitivity at 94% and specificity at 41%. These cut-off values are lower than those maximizing accuracy and allow to reduce the number of false negative results.
  
  
  CONCLUSIONS
  The optimal TE cut-off values to prioritize patients for IFN-free regimens, are sensibly lower than those used to maximize diagnostic accuracy.
authors.affiliation: Department of Internal Medicine, Ospedale A. Manzoni, Lecco, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Colli
authors.affiliation: Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Fraquelli
authors.affiliation: Department of Transfusion Medicine and Hematology, Ospedale A Manzoni, Lecco, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Prati
authors.affiliation: Department of Internal Medicine, Ospedale A. Manzoni, Lecco, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Riva
authors.affiliation: Department of Transfusion Medicine and Hematology, Ospedale A Manzoni, Lecco, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Berzuini
authors.affiliation: Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Conte
authors.affiliation: Gastroenterology and Hepatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Aghemo
authors.affiliation: Gastroenterology and Hepatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Casazza
mesh_terms: D000328:Adult; D000368:Aged; D054459:Elasticity Imaging Techniques; D005260:Female; D019698:Hepatitis C, Chronic / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D006801:Humans; D007372:Interferons; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008875:Middle Aged
chemical_list: D007372:Interferons