Deciding on interferon-free treatment for chronic hepatitis C

Updating liver stiffness cut-off values to maximize benefit

Agostino Colli, Mirella Fraquelli, Daniele Prati, Alessia Riva, Alessandra Berzuini, Dario Conte, Alessio Aghemo, Massimo Colombo, Giovanni Casazza

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Introduction: 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. Aim: 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 IFNfree 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.

Original languageEnglish
Article numbere0164452
JournalPLoS One
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

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chronic hepatitis C
Elasticity Imaging Techniques
Chronic Hepatitis C
interferons
Liver
Interferons
Stiffness
liver
Therapeutics
liver diseases
proteinase inhibitors
endpoints
Ribavirin
Protease Inhibitors
Blood Donors
economics
Liver Diseases
prediction
Blood
blood

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Deciding on interferon-free treatment for chronic hepatitis C : Updating liver stiffness cut-off values to maximize benefit. / Colli, Agostino; Fraquelli, Mirella; Prati, Daniele; Riva, Alessia; Berzuini, Alessandra; Conte, Dario; Aghemo, Alessio; Colombo, Massimo; Casazza, Giovanni.

In: PLoS One, Vol. 11, No. 10, e0164452, 01.10.2016.

Research output: Contribution to journalArticle

Colli, Agostino ; Fraquelli, Mirella ; Prati, Daniele ; Riva, Alessia ; Berzuini, Alessandra ; Conte, Dario ; Aghemo, Alessio ; Colombo, Massimo ; Casazza, Giovanni. / Deciding on interferon-free treatment for chronic hepatitis C : Updating liver stiffness cut-off values to maximize benefit. In: PLoS One. 2016 ; Vol. 11, No. 10.
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