Deciding on Interferon-Free Treatment for Chronic Hepatitis C: Updating Liver Stiffness Cut-Off Values to Maximize Benefit

2016 PLoS ONE 11;10 (e0164452)

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.