**9. Controlled attenuation parameter (CAP) for the noninvasive estimation of steatosis in HCV-infected patients**

Steatosis is a common histological feature and has an important role in the evolution of CHC, in particular in HCV genotype 3 infections [109, 110]. According to a meta-analysis counting 25 studies and 6400 patients, the prevalence of steatosis in CHC patients is estimated at 55.54%, in most cases affecting less than 33% of hepatocytes [111, 112].

Steatosis seems to accelerate fibrosis in the early stages of the disease, reduce treatment response and promote oncogenesis [2, 113, 114]. A recent retrospective study with 515 CHC patients undergoing DAA treatment found a significant correlation between the grade of steatosis and mortality of any cause or HCC development. Furthermore, steatosis surpasses advanced fibrosis regarding the prediction of a poor response to treatment [115]. Steatosis is thus a simple and important predictor of progression in chronic HCV patients.

US is the commonest imaging technique used in clinical practice to diagnose steatosis due to its high accessibility and low cost. However, it is operator- and machine-dependent and the performance is questionable [116, 117]. There is an increasing interest in developing novel tools for steatosis evaluation. At present, the non-invasive parameter, called controlled attenuation parameter (CAP), available on the FibroScan system, is the most validated one. Using the postulate that fat content is directly related to US beam attenuation, CAP enables the diagnosis and quantification of steatosis [118]. Results are expressed in decibels per meter (dB/m), with values ranging from 100 to 400 dB/m.

Several meta-analysis assessed the CAP performance for detecting and grading hepatic steatosis using LB as reference standard [119, 120]. One of the most important meta-analysis dates from 2017 and includes 2735 patients (36.5% with HCV infection) [119]. Results are consistent, so that CAP provided an AUROC of 0.823 (Se = 68.8%, Sp = 82.2%) for detecting mild steatosis (≥S1), 0.865 (Se = 77.3%, Sp = 81.2%) for moderate steatosis (≥S2) and 0.882 (Se = 88.2%, Sp = 77.6%) for severe steatosis (≥S3) [119].

Concerning CHC, we cite 3 studies, one with 854 CHC patients, the other with 115 patients with chronic hepatitis, 76% of them being infected with HCV, and the latter with 201 patients with 118 (58.7%) subjects with HCV infection [121–123]. CAP had good diagnostic accuracy for detecting steatosis and for differentiating between different grades at least two grades apart, independently of fibrosis stage or activity grade. Optimal cutoff values were similar and are presented in **Table 5**. Further validation in large cohorts is however needed in order to validate proper cutoff values. CAP could be ideal as a screening test, as the NPV was high, 0.89–0.87 for ≥S1.


**Table 5.**

*Diagnostic performance of CAP in HCV-infected patients.*

#### **10. Perspectives**

Since shear wave propagation spectroscopy can also provide additional mechanical information on soft tissues, such as viscosity, it might be possible to achieve additional data regarding the utility of 2D-SWE (SSI) for viscosity quantification, a potential marker for necroinflammatory activity [124]. Nonetheless, large cohort prospective studies are required in order to assess the performance of such parameters in biopsied HCV-infected patients.

#### **11. Conclusions**

Elastography-based imaging methods are of high interest nowadays. HCV patients can greatly benefit from VCTE due to its numerous qualities- rapid, noninvasive, repeatable for longitudinal evaluation, and cost-effectiveness. It has great discriminative power for fibrosis assessment, performing better at ruling out cirrhosis rather than diagnosing it, because of high specificity and negative predictive value. In addition, CAP is a precious tool for the noninvasive quantification of steatosis. Further validation in large cohorts is still needed in order to validate cutoff values in CHC patients. Among other elastographic techniques, pSWE and 2D-SWE proved to have the similar diagnostic performance to VCTE for the prediction of fibrosis severity in HCV-infected patients. One of the main advantages of non-invasive techniques is that they opened a new era in HCV management, since it can be easily executed when deemed necessary before antiviral therapy and after HCV eradication, as a repeatable surveillance method. Since the introduction of DAAs in HCV therapy, many patients achieve SVR, which is associated with a reduction in fibrosis. However, clinical practice guidelines do not currently recommend using elastography for the assessment of fibrosis decrease after treatment. Moreover, patients should continue surveillance for decompensation and HCC after SVR, regardless of the result of noninvasive methods.

It is essential that further studies focus on establishing standardized cutoff values of LS for adequate prediction of HCC risk in HCV patients, which is considered to be of great importance in current clinical practice.
