**6. Optimizing the non-invasive diagnosis of portal hypertension using spleen stiffness measurements**

Splenomegaly is a common finding in liver cirrhosis that should determine changes in spleen density as well, because of tissue hyperplasia and fibrosis [85, 86], and/or because of portal and splenic congestion due to the splanchnic hyper-dynamic state [87]. These changes might be quantified by elastography. Until recently, only magnetic resonance elastography (MRE) was used with encouraging results in this respect [88]. The preliminary data showed a highly significant correlation between liver and spleen stiffness in patients with portal hy‐ pertension, but, according to the authors, the validity of spleen stiffness as noninvasive measure of portal venous pressure is not reliable enough [89].

#### **6.1. Principle of TE for Spleen Stiffness Measurements (SSM) and technique assessment**

Our group proposed for the first time the use of FibroScan® for spleen stiffness measure‐ ment (SSM) [90]. For the measurement itself we proposed the same procedure as for the liv‐ er stiffness measurement, with the sole exception that the patient had his left arm in maximum abduction and the transducer was placed in the left intercostal spaces, usually on the posterior axillary line. For better locating the splenic parenchyma, we also used ultra‐ sound guidance, so that we could choose the best location for performing the analysis.

#### **6.2. Efficacy of spleen stiffness measurements for the evaluation of the presence and the grade of esophageal varices**

In another more recent study [91], another group demonstrated that SSM also correlates with HVPG values, suggesting that this new elastographic technique may become a valua‐

Non-Invasive Evaluation of Liver Steatosis, Fibrosis and Cirrhosis in Hepatitis C Virus Infected Patients Using

Unidimensional Transient Elastography (Fibroscan®)

http://dx.doi.org/10.5772/52621

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Regarding the spleen stiffness measurement itself, we observed that the results seem to be influenced by the intrinsic characteristics of the machine (FibroScan). Regardless of the vari‐ ceal status of the patients, or the grade of the varices, SSM reached the maximum value that can be measured by the machine (75 KPa). This is an important drawback, because we have to face a significant interpolation between the patients groups. If the FibroScan had been able to determine values beyond 75 KPa, we may have obtained better figures. In order to overcome this situation, we cooperated with the manufacturer of the device for developing a new calculation algorithm, not available on the commercial device, which allows stiffness measurements of up to 150 kPa. In a validation study [54], using the new calculation algo‐ rithm, we could differentiate between any classes of esophageal varices, except V1 vs V2 (p<0.005) and could select patients with V3 (V012 vs V3 = 63.49 vs 116.08 kPa, p<0.005), the

**7. Noninvasive evaluation of liver steatosis using Controlled Attenuation**

Even though liver stiffness provides an alternative to liver biopsy for fibrosis staging, it can identify very important histologic features such as macrovesicular steatosis, ballooned hepa‐

**Figure 4.** Boxplots representing mean SSM values according to the esophageal varices grade using the original (A) or

Knowing that fat interferes with ultrasound propagation, a novel attenuation parameter has been developed to detect and quantify liver steatosis. This parameter is based on the ultra‐

**6.3. Improving diagnostic accuracy for esophageal varices by modifying the SSM**

ble noninvasive method for liver cirrhosis patients

ones that are at higher risk for bleeding (figure 4).

**calculation algorithm**

**Parameter (CAP)**

tocytes, inflammation, etc [68].

the modified (B) calculation algorithm.

In the above mentioned study, we demonstrated that spleen stiffness can be assessed using transient elastography, the sole factor influencing the measurement being the spleen size. Spleen stiffness increases as the liver disease worsens, from normal to chronic hepatitis and to liver cirrhosis (figure 2).

**Figure 2.** A - Box plots of spleen stiffness values for controls (0), chronic hepatitis (1) and cirrhosis patients (2). The top and the bottom of the boxes are the first and third quartiles, respectively. The length of the box thus represents the interquartile range within which 50% of the values were located. The line through the middle of each box represents the median. The error shows the minimum and maximum values (range); B - Graphic representation of the significant increase of SSM in healthy controls and patients with chronic hepatitis and liver cirrhosis, respectively.

In liver cirrhosis patients, the spleen stiffness measurement, can predict the presence, but not the grade of esophageal varices. Therefore, for a cutoff value of 46.4 kPa, we managed to predict the presence of esophageal varices with a diagnostic accuracy of 80.45% and an AU‐ ROC of 0.781 (figure 3).

**Figure 3.** A - Box plots showing the increase of SSM in liver cirrhosis patients with esophageal varices as compared with those without; B - ROC curve representation of SSM in distinguishing LC patients with or without EV.

In another more recent study [91], another group demonstrated that SSM also correlates with HVPG values, suggesting that this new elastographic technique may become a valua‐ ble noninvasive method for liver cirrhosis patients

#### **6.3. Improving diagnostic accuracy for esophageal varices by modifying the SSM calculation algorithm**

**6.2. Efficacy of spleen stiffness measurements for the evaluation of the presence and the**

In the above mentioned study, we demonstrated that spleen stiffness can be assessed using transient elastography, the sole factor influencing the measurement being the spleen size. Spleen stiffness increases as the liver disease worsens, from normal to chronic hepatitis and

**Figure 2.** A - Box plots of spleen stiffness values for controls (0), chronic hepatitis (1) and cirrhosis patients (2). The top and the bottom of the boxes are the first and third quartiles, respectively. The length of the box thus represents the interquartile range within which 50% of the values were located. The line through the middle of each box represents the median. The error shows the minimum and maximum values (range); B - Graphic representation of the significant

In liver cirrhosis patients, the spleen stiffness measurement, can predict the presence, but not the grade of esophageal varices. Therefore, for a cutoff value of 46.4 kPa, we managed to predict the presence of esophageal varices with a diagnostic accuracy of 80.45% and an AU‐

**Figure 3.** A - Box plots showing the increase of SSM in liver cirrhosis patients with esophageal varices as compared

with those without; B - ROC curve representation of SSM in distinguishing LC patients with or without EV.

increase of SSM in healthy controls and patients with chronic hepatitis and liver cirrhosis, respectively.

**grade of esophageal varices**

222 Liver Biopsy – Indications, Procedures, Results

to liver cirrhosis (figure 2).

ROC of 0.781 (figure 3).

Regarding the spleen stiffness measurement itself, we observed that the results seem to be influenced by the intrinsic characteristics of the machine (FibroScan). Regardless of the vari‐ ceal status of the patients, or the grade of the varices, SSM reached the maximum value that can be measured by the machine (75 KPa). This is an important drawback, because we have to face a significant interpolation between the patients groups. If the FibroScan had been able to determine values beyond 75 KPa, we may have obtained better figures. In order to overcome this situation, we cooperated with the manufacturer of the device for developing a new calculation algorithm, not available on the commercial device, which allows stiffness measurements of up to 150 kPa. In a validation study [54], using the new calculation algo‐ rithm, we could differentiate between any classes of esophageal varices, except V1 vs V2 (p<0.005) and could select patients with V3 (V012 vs V3 = 63.49 vs 116.08 kPa, p<0.005), the ones that are at higher risk for bleeding (figure 4).
