The New Era for Liver Fibrosis: The Non Invasive Assessment in Hepatitis C Virus Infected Patients

Editorial

The term “elastography” refers to a variety of techniques able to characterize the response and mechanical properties of tissues using non-invasive methods. Hepatic elastography has been shown to be an effective technique for diagnosing of severe fibrosis and for excluding a significant fibrosis. It may be used as a “diagnostic discriminator” to establish clinical priorities and reduce the number of liver biopsies [1].

New treatments for HCV infection require an accurate assessment of liver fibrosis for a correct therapeutic approach. The assessment of liver stiffness by Transient Elastography (TE) is a good option to evaluate liver fibrosis by non invasive method for accurate selection of patients’ treatment. Its accuracy for the diagnosis of liver fibrosis largely depends on the choice of correct cut-offs values. Recently, Ferraioli et al [2]. Compared results of liver stiffness measurement obtained in 246 patients (79.3% HCV) with those of a recent metaanalysis by Tsochatzis et al [3]. The cut-offs of the single centre study by Ferraioli et al [2]. were comparable to those obtained in the metaanalysis that included 40 studies. In this meta-analysis the cut-offs values were 7.6 (range 5.1–10.1), 10.9 (8.0–15.4), and 15.3 (11.9–26.5) kPa for F = 2, 3, and 4, respectively.

The meal can affect the reliability of stiffness values in the diagnosis of fibrosis stage in patients with chronic HCV infection [3, 4]. A recent study [5] suggests that should be observed a fasting period of 120 min before liver stiffness measurements. In this study liver stiffness was performed in 125 consecutive patients with chronic HCV infection in different stages of fibrotic evolution. Stiffness values were measured at different time point after a standardized liquid meal. A peak in the increase of stiffness values were observed between 15-45 minutes after the start of the meal with a return to pre-meal baseline values within 120 minutes in all patients. Several studies [6-11] have evaluated the utility of TE for the assessment of short- and long-term longitudinal changes in liver fibrosis before, during, and after antiviral treatment in patients with chronic HCV infection. The results of these studies show that this technique may detect changes of liver fibrosis during treatment thus may be useful for the clinical management of chronic liver disease. Moreover, Stasi et al. [11,12] showed that high liver stiffness values may also be considered as a negative

predictive value of response to treatment. In these studies [11,12], patients with stiffness values greater than 12 kPa had a significant lower response to antiviral therapy, suggesting that measurement of liver stiffness could be considered together with other predictors of response when considering treatment [11,13]. The assessment of liver stiffness in patients with HCV-mixed cryoglobulinemia syndrome undergoing Rituximab treatment, in whom antiviral treatment was contraindicated or not tolerated, showed a reduction of liver stiffness, strictly associated with the B-cell depletion, at month 3 after therapy compared to baseline values. This data suggest a role of liver infiltrates and subsequent liver necro-inflammation, as already shown in previous study [14,15].

An international multicentre study [16] compared the accuracy of Acustic Radiation Force Impulse (ARFI) elastography in the detection of fibrosis in comparison with liver biopsy and TE. The results of this study showed that TE was more accurate for all stage of Fibrosis (F=1) and cirrhosis, while the accuracy of ARFI and TE was similar when these were used to predict significant (F=2) and severe fibrosis (F=3).

The accuracy of abdominal ultrasound, computer tomography or MR imaging, in the diagnosis of liver fibrosis is limited. MR imaging does not visualize the precirrhotic stage of liver fibrosis and the early cirrhosis. In these conditions, in MR imaging liver parenchyma appear normal. The assessment of liver fibrosis improve trough the administration of contrast agents. In particular, double contrastenhanced MR imaging causes high image contrast between the lowsignal- intensity fibrotic reticulations. However, the main limitation of this technique is the high cost and the inconvenience related with the use of two contrasts [17].

MR elastography is a new technique that quantifies stiffness of the liver with a sufficient reproducibility [18,19] and high diagnostic accuracy for staging liver fibrosis. Ichikawa et al [20] compared the ability of MR elastography and serum fibrosis markers to discriminate different stages of fibrosis. They found that mean stiffness value of the liver increased as liver fibrosis stage progressed. In comparison with TE, the advantage of MR elastography is that this technique visualizes the whole liver and does not require a specific acoustic window. Its main limitations are the high cost and inconvenience associated with confounding factors such us hepatic inflammation [21], hepatic vascular congestion, cholestasis and portal hypertension [17]. Although steatosis itself does not affect the stiffness measurements, fat deposition can cause inflammation, with consequent increase of liver stiffness, even before the onset of fibrosis [21]. Moreover, as already shown for TE, even in MR, the meal can affect the reliability of stiffness measurements, suggesting the need of fasting prior to perform the exam [22].

In conclusion, the results of several studies suggest that the wider availability of non invasive test for the assessment of liver fibrosis may soon date the way for a reduced need of liver biopsy in patients with chronic liver disease HCV-related.

Acknowledgement

I would like to gratefully and sincerely thank Prof. Milani S. for critically reviewing the manuscript.

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