**4. Vibration controlled transient elastography performance for fibrosis staging in HCV-infected patients**

As already mentioned, staging fibrosis is beneficial to determine the prognosis and follow-up of patients with chronic HCV infection. VCTE is the most validated elastographic modality in this regard. Several meta-analysis found an excellent diagnostic performance of VCTE in diagnosing hepatic cirrhosis, with an AUROC exceeding 0.90. However, the technique is less accurate in case of significant fibrosis (≥F2), with an AUROC ranging between 0.80 and 0.90 with overlapping cutoff values, so that the method is facing difficulties in distinguishing different stages of fibrosis [30–34]. Concerning CHC, two of these meta-analysis reported AUROC values of 0.83–0.85 and 0.96 for diagnosing significant fibrosis and cirrhosis, respectively [31, 33]. EASL guidelines suggest combining VCTE with serological markers for the assessment of moderate fibrosis (F2-F4) in patients with CHC [6].

A recent meta-analysis counting 24 articles evaluated the performance of VCTE for diagnosing liver cirrhosis in CHC patients. It estimated a sensitivity (Se) of 84% and a specificity (Sp) of 90%, with AUROC 0.95 [35]. Ganne-Carrié suggests in a study with 775 patients that VCTE should be particularly used for ruling out cirrhosis, given its high negative predictive value (NPV) (96%), rather than ruling it in, since the positive predictive value (PPV) was only 74%. Nevertheless, the excellent diagnostic performance for cirrhosis is hereby confirmed [36].

A recent study [37] compares the performance of VCTE with conventional B-mode ultrasound (US). VCTE is clearly superior in diagnosing severe fibrosis and subclinical cirrhosis, with an AUROC of 0.95 for severe fibrosis and 0.96 for cirrhosis versus 0.76 and 0.71, respectively, in the case of US (p < 0.001). Furthermore, combining the two methods does not significantly improve diagnostic accuracy compared with VCTE alone. The two would improve Sp (95.7% versus 76.7; p < 0.001) and PPV (94.3% versus 77.1%; p = 0.002) [37]. Another study by Berzigotti et al. [38] suggests that the two methods work complementary so that US is the preferred technique for ruling in cirrhosis, while VCTE should be used for ruling out the disease. Contrary to the first example, Benzigotti claims a better performance when the two are combined.

The diagnostic performance of VCTE in staging fibrosis is exemplified in **Table 2**, in reliance to our previous research [50]. Cutoff values range from 4.5 to 9.5 kPa for significant fibrosis (≥F2) and from 11.3 to 16.9 kPa for diagnosing cirrhosis (F4). These values vary considerably mainly according to the prevalence of fibrosis in each study group and the expected outcome [51].
