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 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.