Influence of Food Intake on 2-D Shear Wave Elastography Assessment of Liver Stiffness in Healthy Subjects

Abstract

Transient elastography and Acoustic Radiation Force Impulse imaging are useful non-invasive methods for liver stiffness estimation, although both are influenced by food intake. The aim of the work described here was to identify liver stiffness variation after a standardized meal using 2-D shear wave elastography. Liver stiffness was estimated in 31 apparently healthy subjects, under fasting conditions and after a standardized meal (20, 40, 60, 80, 100 and 120 min after food intake). In most of the cases, liver stiffness values increased between 20 and 40 min after the meal (p < 0.05) and then significantly decreased between 60 and 80 min (p < 0.05). At 120 min after food intake, liver stiffness values were significantly lower compared with liver stiffness values under fasting conditions (p < 0.05). Gender, but not body mass index, had an important role in liver stiffness variation after food intake (p < 0.01). In conclusion, to avoid the influence of food intake on liver stiffness estimation, 2-D shear wave elastography should be performed only under fasting conditions.

Introduction

Liver fibrosis occurs as a consequence of chronic liver injuries and is most commonly encountered in chronic viral hepatitis and alcoholic and non-alcoholic steatohepatitis (Sebastiani et al. 2011). One of the main goals of ongoing research is to improve the patient's quality of life by identifying fibrosis associated with the underlying disease so that measures that would delay the associated complications can be undertaken. In chronic viral hepatitis, fibrosis stage ≥F2 is an important element in recommending antiviral treatment (Wang et al., 2012a, Ziol et al., 2005).

Liver biopsy is considered the method of choice for diagnosing and staging liver fibrosis despite its recognized limitations, such as ≤30% false-negative results and high inter- and intra-observer variability (Bedossa et al., 2003, Regev et al., 2002). Also, post-procedural complications cannot be neglected: in about 1%–3% of cases; complications requiring medical care, caused mainly by hypotension and pain, have been reported (Bravo et al. 2001). Today, the research in this domain is progressively focused on developing and improving non-invasive methods for estimating liver fibrosis, such as serologic markers and imaging technologies.

Among all non-invasive methods used for liver stiffness estimation, elastography is the one most commonly used, with a good predictability for liver fibrosis (Chon et al., 2012, Friedrich-Rust et al., 2008, Friedrich-Rust et al., 2012, Samir et al., 2014, Wang et al., 2012b). A complete classification of the elastography methods, according to the EFSUMB Guidelines and Recommendations, is detailed in Table 1 (Bamber et al. 2013).

Some factors have already been proven to influence liver stiffness estimation using elastography techniques. To avoid misleading increased liver stiffness assessment, all confounding factors must be taken into account and excluded as much as possible. Among these factors, food intake has an important role in defining liver stiffness because of changes in intrahepatic vascularization (Dauzat et al., 1994, Zardi et al., 2008). Both transient elastography (TE) and Acoustic Radiation Force Impulse (ARFI) imaging are influenced by food intake; liver stiffness values increase starting 15 min after meal and return to baseline values about 2–3 h after the meal (Arena et al., 2013, Goertz et al., 2012, Mederacke et al., 2009, Popescu et al., 2013).

It is well documented that about 15–40 min after food intake, hemodynamic changes occur in splanchnic vessels, with differences between healthy subjects and patients with cirrhosis (Dauzat et al., 1994, Zardi et al., 2008). Because of these changes, liver stiffness prediction with TE and ARFI methods is not reliable immediately after food intake (Arena et al., 2013, Goertz et al., 2012, Mederacke et al., 2009, Popescu et al., 2013).

Using transient elastography, Mederacke et al. (2009), in 12 apparently healthy subjects, measured an overall increase in liver stiffness of 20% immediately after a meal (from 4 ± 0.7 to 4.8 ± 0.9 kPa), with a mean peak value up to 24% after food intake (4.0 ± 0.7 to 5.1 ± 0.9 kPa).

Arena et al. (2013) found that liver stiffness increases more conspicuously in patients with cirrhosis than in healthy subjects or patients with chronic hepatitis, as predicted by TE. In the same study, mean liver stiffness values increased 30 min post-prandially by up to 24% of baseline values in patients with chronic hepatitis stage F0–F1, with mean peak values up to 33%; then, 120 min after the meal, liver stiffness returned to baseline values. In the control group, which had water instead of food, the mean values of liver stiffness were not modified at all, and the mean peak values were only 3.7% higher for all measurements (Arena et al. 2013).

Popescu et al. (2013) used ARFI elastography to analyze liver stiffness before and after a standardized meal in healthy volunteers. The authors described a significant increase in liver stiffness values (>15% of baseline values) 1 h after the meal in 45.7% of the subjects. At the same time, in 50.8% of cases, they observed modest increases in liver stiffness (≤15% of baseline values). In the remaining 3.5% of cases, there were lower liver stiffness values 1 h after the meal compared with fasting conditions (>15% of baseline values). Within 3 h after the meal, liver stiffness values did not significantly differ from the values in the control study (Popescu et al. 2013); liver measurements made only under fasting conditions and 1 and 3 h after the meal and the complete curve of the liver stiffness after food intake could not be established. In the study group, mean liver stiffness before the meal was 1.27 ± 0.23 m/s, within 1 h after the meal it was 1.51 ± 0.40 m/s, and within 3 h after the meal, mean liver stiffness was 1.46 ± 0.51 m/s (Popescu et al. 2013). Within 1 h after the meal, mean liver stiffness measured by ARFI elastography increased by 19% compared with fasting conditions. In the control group, 1 h after the first measurement, the mean stiffness was similar to the first measurement (1.28 ± 0.21 m/s vs. 1.22 ± 0.19 m/s). It is worth noting that maintaining the same depth for each measurement per subject was not mentioned in the study design, which is an important parameter for multiple liver stiffness measurements with ARFI and 2-D shear wave elastography (SWE) (Huang et al., 2014, Potthoff et al., 2013).

In a similar study, Goertz et al. (2012) compared liver stiffness values of the same patients before and after food intake. At 30 min after the meal, the authors reported a significantly higher (≤8.74%) mean liver stiffness value (1.03 ± 0.10 m/s vs. 1.12 ± 0.11 m/s).

Two-dimensional shear-wave elastography is a relatively new elastographic ultrasound technique, with promising results in prediction, assessment and diagnosis of significant liver fibrosis (Samir et al. 2014). Liver stiffness estimation using 2-D SWE performed on the same day has been reported to have an intra-class correlation coefficient (ICC) ≤0.95 (Yoon et al. 2014). This type of elastography is able to express hepatic elasticity both as the velocity of the shear wave (m/s) and in absolute elasticity modulus units (kPa).

To the best of our knowledge, there are no published studies on the influence of food intake on liver stiffness values, as measured by SWE with an Aixplorer ultrasound system (SuperSonic Imagine). The aims of this study were to assess the influence of food intake on liver stiffness values estimated by 2-D SWE and to explore the importance of body mass index (BMI) and gender on liver stiffness variation after a standardized meal.