Gut and Liver 2017; 11(4): 464-473 https://doi.org/10.5009/gnl16078 Ultrasonography for Noninvasive Assessment of Portal Hypertension
Author Information
Hitoshi Maruyama, and Osamu Yokosuka
Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan

Hitoshi Maruyama, Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan, Tel: +81-43-2262083, Fax: +81-43-2262088, E-mail: maru-cib@umin.ac.jp
© The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract

Portal hypertension is a major pathophysiology in patients with cirrhosis. Portal pressure is the gold standard to evaluate the severity of portal hypertension, and radiological intervention is the only procedure for pressure measurement. Ultrasound (US) is a simple and noninvasive imaging modality available worldwide. B-mode imaging allows broad applications for patients to detect and characterize chronic liver diseases and focal hepatic lesions. The Doppler technique offers real-time observation of blood flow with qualitative and quantitative assessments, and the application of microbubble-based contrast agents has improved the detectability of peripheral blood flow. In addition, elastography for the liver and spleen covers a wider field beyond the original purpose of fibrosis assessment. These developments enhance the practical use of US in the evaluation of portal hemodynamic abnormalities. This article reviews the recent progress of US in the assessment of portal hypertension.

Keywords: Ultrasonography, Doppler, Contrast media, Liver, Hypertension, portal
Abstract

Portal hypertension is a major pathophysiology in patients with cirrhosis. Portal pressure is the gold standard to evaluate the severity of portal hypertension, and radiological intervention is the only procedure for pressure measurement. Ultrasound (US) is a simple and noninvasive imaging modality available worldwide. B-mode imaging allows broad applications for patients to detect and characterize chronic liver diseases and focal hepatic lesions. The Doppler technique offers real-time observation of blood flow with qualitative and quantitative assessments, and the application of microbubble-based contrast agents has improved the detectability of peripheral blood flow. In addition, elastography for the liver and spleen covers a wider field beyond the original purpose of fibrosis assessment. These developments enhance the practical use of US in the evaluation of portal hemodynamic abnormalities. This article reviews the recent progress of US in the assessment of portal hypertension.

Keywords: Ultrasonography, Doppler, Contrast media, Liver, Hypertension, portal
INTRODUCTION

Because of the close relationship with disease severity, portal hemodynamics is the key pathophysiology in cirrhosis.13 The development of collateral vessels represents a portal abnormality, which results in gastroesophageal varices, ectopic varices, and hepatic encephalopathy; these are the major manifestations in cirrhosis.46 A proper management may be the key issue in clinical practice because the complications caused by portal hypertension affect the prognosis and quality of life of cirrhosis patients.7,8

The severity of portal hypertension is determined by the portal pressure.7,9 Performing interventional radiology (IVR) may be the only procedure to obtain the hepatic venous pressure gradient (HVPG), a surrogate marker for directly measured portal pressure. However, because of its invasiveness under radiation exposure, noninvasive markers available for repeated use during the long-term clinical course may be preferable.1,10

Because of simple and less-invasive evaluations, ultrasound (US) may be the most frequently used imaging procedure in the practical management of patients with chronic liver disease.4,5 Doppler mode enables real-time observation of blood flow under physiological conditions, and contrast-enhanced US with microbubble contrast agents allows detailed assessment of peripheral blood flow. In addition, elastography for liver and spleen shows broad application beyond the original purpose of fibrosis assessment. Clearly, such advancement is supported by the development of digital technologies and diffusion of information. With this background, this review article describes the recent progress of using US in the noninvasive assessment of portal hypertension.

B-MODE US

Recent developments in digital technology have introduced various imaging modes, color/power Doppler, harmonic imaging for contrast enhancement, three-dimensional visualization, and fusion imaging.1,4,11 However, fundamental tissue images are available only using B-mode sonography. The role of this simple technique for portal hypertension is to characterize cirrhosis, measure vessel diameter and spleen size, and identify the ascites and abnormal collateral route.1214 However, because they are indirect findings to suspect the presence of portal hypertension, benefits of B-mode US on the prediction of portal pressure and the assessment of the severity of portal hypertension are limited.

DOPPLER US

With the advantage of real-time observation of blood flow under physiological conditions, studies using Doppler US have been performed for evaluating the severity of liver disease and portal hypertension (Fig. 1).1,4,6,1518 Indeed, portal hemodynamics are predictive markers of outcomes in cirrhosis, lower velocity (<12.8 cm/s) in the portal trunk in compensated cirrhosis for decompensation, and reverse portal flow in decompensated cirrhosis for poor prognosis (Table 1).19 However, a major issue is the prediction of HVPG, which is a standard maker for the severity of portal hypertension. According to a Korean study, patients with a damping index (minimum velocity/maximum velocity of the hepatic vein waveform) >0.6 are significantly more likely to have severe portal hypertension (SPH; HVPG >12 mm Hg), with 76% sensitivity and 82% specificity, suggesting an effective parameter to predict the grade of portal hypertension (Table 1).20 In another study, in 66 patients with hepatitis C virus infection, there were significant correlations between HVPG and intraparenchymal splenic artery resistance index (SA-RI) (r=0.50, p<0.0001), superior mesenteric artery-pulsatility index (SMA-PI) (r=−0,48, p<0.0001), and right interlobar renal artery resistance index (RRA-RI) (r=0.51, p<0.0001) (Table 1).21 However, dividing patients according to the presence or absence of SPH, correlations between HVPG and intraparenchymal SARI (r=0.70, p<0.0001), SMA-PI (r=−0.49, p=0.02), and RRA-RI (r=0.66, p=0.0002) were observed only in patients with HVPG <12 mm Hg. The HVPG but not Doppler parameters correlated with the presence of esophageal varices (EV; p<0.0001). Indeed, the negative aspect of the Doppler US may be enhanced in late years because of less statistical power for the prediction of clinically significant portal hypertension (CSPH; HVPG >10 mm Hg) and EV.22 The effect of Doppler US to predict the severity of portal hypertension may still be debated due to the lack of a definitive parameter.

CONTRAST-ENHANCED US

1. Contrast-enhanced US and portal hypertension

With its simplicity and safety, contrast-enhanced US has become popular for assessing liver disease.2326 Currently, it is applied in the wide range of liver diseases to differentiate diffuse liver diseases and assess the severity of portal hypertension, in addition to the management of focal hepatic lesions.411

The interval time between vessels is a representative parameter for microbubble hemodynamics and shows close correlation with portal pressure, between free portal pressure and hepatic vein–hepatic artery interval time (r=−0.804, p=0.009) or the portal vein–hepatic artery interval time (r=0.506, p=0.036).27 More recent studies have demonstrated original parameters for portal pressure; the first study proposed “regional hepatic perfusion” using SonoVue, which correlated with HVPG (r=0.279, p=0.041) and hyperdynamic syndrome markers.28 The other study has shown that the portal vein/hepatic artery time-intensity curve ratio, portal vein/hepatic artery strength ratio, and portal vein/hepatic artery wash-in perfusion slope ratio have close correlation with portal pressure.29

2. Diagnostic ability for portal hypertension

Three studies reported the actual diagnostic value of contrast parameters for the severity of portal hypertension (Table 2). The first two studies, both from South Korea, used hepatic transit time as a contrast parameter. A study by Kim et al.30 reported that the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and area under the receiver operating curve (AUROC) of transit time from the venous access to the hepatic vein (hepatic vein arrival time, HVAT) using SonoVue (cutoff value, 14 seconds) were 92.7%, 86.7%, 90.5%, 89.7%, 6.95, 0.08, and 0.973, respectively, on the prediction of CSPH in compensated cirrhosis. The next study compared the two parameters using SonoVue, HVAT, and intrahepatic transit time in 53 cirrhosis patients. Both showed significant differences between patients <12 mm Hg and those ≥12 mm Hg; however, the diagnostic abilities were higher in the latter (sensitivity, 85.3%; specificity, 91.2%; AUROC, 0.94) than in the former (sensitivity, 58.1%; specificity, 62.8%; AUROC, 0.72).31 The last study focused on the splenic circulation (i.e., the traveling time of microbubbles from splenic artery to splenic vein).32 The AU-ROC was 0.76 for CSPH with best cutoff value of 13.5 seconds and 0.76 for SPH with best cutoff value of 14.5 seconds.

3. Subharmonic imaging

The subharmonic mode is a novel technique using a characteristic property of microbubble. An early study in canines reported the possibility of a subharmonic aided pressure estimation (SHAPE) in the estimation of portal pressure.33 The same group examined the clinical effect of the technique in human subjects and found a good overall agreement (r=0.82) between the SHAPE gradient (the portal and hepatic veins) and HVPG.34 The diagnostic abilities of the SHAPE were 89% sensitivity and 88% specificity for patients with CSPH and 100% sensitivity and 81% specificity for patients with SPH. These data suggest the potential of this novel parameter as a noninvasive marker for the severity of portal hypertension.

ELASTOGRAPHY

1. Transient elastography for liver stiffness

Although the original application of transient elastography (TE) was assessing the fibrosis grade in the liver, recent studies have expanded the use of TE to evaluate potential liver function, severity of portal hypertension, and risk of cancer development.1,10,35

A significant relationship between the HVPG and liver stiffness (LS) by TE has been reported,36 and its actual diagnostic ability may be acceptable because the AUROC is ≥0.8,3743 except for two studies showing an AUROC of 0.76 and 0.78 (Table 3).41,44 The accuracy of LS for SPH was significantly higher than that of Plt (platelet count)/Spl (spleen diameter) (AUROC: LS, 0.919 vs Plt/Spl, 0.828; p=0.038).45 However, some studies suggested that the linkage between LS and HVPG was dominant in mild or moderate grade portal hypertension, presented by HVPG <10–12 mm Hg, and not in the severe grade in hepatitis C virus-related cirrhosis patients.37,44 The reasons for the poor correlation in advanced portal hypertension may be the presence of extrahepatic changes in the portal hemodynamics and the influence of various factors, such as cholestasis and inflammation, on the LS value.46

The diagnostic ability by LS for EV was summarized in Table 4; even for large EV, the AUROC remains 0.75 to 0.87.38,47,48 These poor abilities are supported by a recent meta-analysis study: 87% sensitivity and 53% specificity for EV and 86% sensitivity and 59% specificity for large EV.49 Because of this insufficient ability, particularly poor specificity, replacement of endoscopy by TE alone may not be presently encouraged.

Recently, two studies focused on the other practical use of LS value, that is, the prediction of complications caused by portal hypertension. According to the study by Kitson et al.,40 although LS >29 kPa was effective to identify CSPH, the prediction of complications related to portal hypertension showed 100% sensitivity with only 40% specificity. Meanwhile, the optimal cutoff value of 34.5 kPa provided 75.0% sensitivity, 69.4% specificity, 52.5% PPV, 86.2% NPV, PLR 2.5, and NLR 0.36 for the prediction of complications. Furthermore, a study in 100 patients (mean follow-up period, 491 days) with chronic liver disease has shown that LS is as effective as HVPG in predicting clinical decompensation and complications caused by portal hypertension.50

Although the waveform patterns in the hepatic vein show a close relationship with the severity of liver disease, the underlying mechanism for various patterns had been undetermined. A study by Sekimoto et al.51 reported the linkage between waveform patterns and LS, which may be a major pathogenesis to determine the waveform patterns in the hepatic vein.

2. TE combined with other factors

The addition of other factors may increase the diagnostic performance of TE. The AUROC of LS and Liver stiffness, spleen size, and platelet count (LS×spleen size/platelet count) for CSPH was 0.883 and 0.918 in the training set and 0.901 and 0.906 in the validation set, respectively.52 Another study also reported that combining LS with platelet count improved diagnostic accuracy in the exclusion of CSPH; an LS >29.0 kPa predicted CSPH with 71.9% sensitivity, 100% specificity, 100% PPV, and 56.0% NPV. An LS <25.0 kPa in those with platelet count >150×109/L excluded CSPH with 91.7% sensitivity, 100% specificity, 100% PPV, and 90% NPV.40

As for the diagnosis of gastroesophageal varices, a combined model with LS and platelet count was more accurate for excluding the presence of high-risk gastroesophageal varices than either alone (training cohort AUROC: 0.87 [0.77–0.96] vs 0.78 [0.65–0.92] for LS and 0.71 [0.52–0.90] for platelets) with the combination of LS ≤25 kPa and platelets ≥100 having an NPV of 100% in both the training and validation cohorts.53 However, a more recent study performed in 219 alcoholic cirrhosis patients showed that none of the noninvasive tests, including aspartate aminotransferase-to-platelet ratio index, FIB-4, Forns index, Lok index, (platelet count)2/(monocyte fraction [%]×segmented neutrophil fraction [%]), and platelet count to spleen diameter ratio showed reliable performance (AUROCs of all investigated tests <0.70).54 According to the study by Procopet et al.,55 the use of artificial neural networks integrating different noninvasive tests did not increase the diagnostic accuracy of LS alone, which was the best way to assess the presence of cirrhosis, portal hypertension, and EV. Thus, the combined effect depends on the parameters, and further investigation may be required to seek better markers, particularly for the diagnosis and grading of EV.

3. Reliability in the TE measurement

It is generally believed that LS values obtained by TE are considered reliable with the traditional criteria, valid measurements of 10 times or more, a success rate >60%,56,57 and a quotient of interquartile range per median (IQR/M) <0.30.58 However, LS data are affected by several factors: sex,59 levels of aminotransferases,60,61 histological inflammation,62,63 extrahepatic cholestasis,64,65 liver steatosis,39,66,67 body mass index,68,69 fasting state,70,71 and central venous pressure.72 Therefore, further improvement of reliability is clearly required in TE measurement, and indeed, some studies have indicated problems in the traditional criteria and suggested room for improvement.69,7375

Boursier et al.76 proposed new reliability criteria: “very reliable” (IQR/M≤0.10), “reliable” (0.100.30 with LS median<7.1 kPa), and “poorly reliable” (IQR/M>0.30 with LS median≥7.1 kPa). A more recent study compared traditional and new TE quality criteria (very reliable by IQR/M<0.1, and reliable by IQR<0.3 or >0.3, if TE<7.1 kPa) regarding their diagnostic accuracy for cirrhosis and portal hypertension83 and found that the latter increases the number of patients with accurate measurements without affecting diagnostic performance for detecting cirrhosis and portal hypertension.

4. Acoustic radiation force impulse and share wave elastography

Acoustic radiation force impulse (ARFI) and share wave elastography (SWE) are modalities using US-based impulse instead of mechanical impulse for TE. An early study reported an increase of share wave velocity in parallel with the increase of the splenic index (ρ=0.409, p<0.01) and splenoportal index (ρ=0.451, p<0.01).84

In the study by Morishita et al.,80 AUROC values for the presence of EV and high-risk EVs by ARFI were 0.890 and 0.868, respectively, which had the highest diagnostic performance among factors, including serum fibrosis markers (Table 4). The diagnostic accuracy of LS by ARFI was comparable to TE and Fibrotest for the detection of complications in patients with cirrhosis.85 As for the portal pressure, data obtained by SWE (SuperSonic) showed significant correlation with the HVPG and feasibility to estimate the change in HVPG due to the medication by non-selective β-blocker in patients with portal hypertension.86

Another issue is the lack of reliability criteria for the measurement of real-time SWE. A recent study demonstrated that standard deviation/median ≤10 and/or depth <5.6 cm are considered reliable criteria in the assessment of CSPH.87

5. Spleen stiffness

Spleen is another target of elasticity measurement, and investigators have shown the benefits of spleen stiffness (SS) measurement. Two studies reported significant correlations between SS and HVPG, with SS (r=0.433, p=0.001), but not with LS (r=0.178, p=0.20) by Sharma et al.81 and with SS (r=0.885, p=0.0001) and LS (r=0.836, p=0.0001).45 In fact, SS appears to provide better diagnostic performances for detecting EV compared to other noninvasive markers (Table 4).

Prospective comparison of SS and LS by using SWE and TE for detection of portal hypertension in cirrhosis was conducted by Elkrief et al.41 In patients with advanced cirrhosis who are undergoing HVPG measurements, LS measurements obtained by using SWE have a higher technical success rate and a better diagnostic value than TE for CSPH. A more recent study has shown that SS can noninvasively assess changes in portal pressure after liver transplantation and decreases significantly when portal hypertension resolves.88

As expected, a combination of LS with SS may be effective to predict the severity of portal hypertension; the accuracy to predict significant EV was 69.6% to 70.8% using the formula with both LS and SS “−0.572+0.041×LS (m/s)+0.122×SS (m/s)+ 0.325×ascites (1, absent; 2, present).”89

CHALLENGES AND FUTURE DIRECTIONS

Strength/advantage and weakness/disadvantage of various US-based techniques are summarized in Table 5. Against their apparent benefits, there are still some limitations in each modality.

Unfortunately, the diagnostic ability of Doppler parameters for portal hypertension is unsatisfactory, making the clinical application limited, and therefore alternative parameters are required with a hard/software development.

As for the contrast-enhanced US, the major problem is the limited availability of contrast agents and still, there is no available agents in some countries. Next is that because the dynamics and metabolism of in vivo microbubble have not been fully examined, the interpretation of contrast findings needs further investigation.

An establishment of reliability criteria and an improved assessment for patients with unreliable data should be considered in the field of elastography.

And finally, noninvasive diagnosis of EV is facing poor diagnostic performance. There are still challenges in the research field, suggesting our future directions for the improvement of diagnostic ability by achieving the international study with large patient population.

CONCLUSIONS

The present review article clearly demonstrates various benefits of US in the assessment of portal hypertension. Because of a close relationship with impaired portal hemodynamics, Doppler measurement data are useful to understand the underlying pathogenesis in the portal system. However, as the currently available parameters are not definitive indicator for HVPG, continuous efforts are required to determine the appropriate Doppler markers.

As for contrast-enhanced US, quantitative evaluation of microbubble behavior allows comprehensive assessment of portal hemodynamics, resulting in the efficient prediction of severity of portal hypertension.

Elastography may have an advantage of simplicity and reproducibility over Doppler/contrast mode and shows improved diagnostic ability to estimate the severity of portal hypertension. Moreover, recent studies suggest that multiple factor-based combined parameters are superior to a single modality-based parameter in the diagnostic performance.

It is expected that further development of technology (hardware and software) would make the role of US dominant in the current IVR-based diagnosis and grading of portal hypertension.

Figures
Fig. 1. Pulsed Doppler image for portal trunk (68-year-old male, non-B, non-C cirrhosis). The portal trunk was demonstrated as a longitudinal view and sample volume was used with the optimal width to include the vessel. Time-averaged mean flow velocity was obtained from the waveform of the Doppler signal with the beam-vessel angle, which was 60 degrees or smaller. Flow volume was calculated by multiplying mean flow velocity by automatic cross-section of the vessel every 60 seconds.
Tables

Diagnostic Ability of Doppler Parameters

StudyPatients, no.EtiologyParameterCutoff valueDiagnosisSe/Sp/PPV/NPVAUROC
Kondo et al.19236MixVelocity12.8 cm/sDecompensation68/75/68/750.7395
Flow directionReversePrognosis21.8/99.3/70.6/60.6-
Kim et al.2076MixDamping index*0.6SPH75.9/81.8/91.1/58.10.860
Vizzutti et al.2166HCVSA-RI0.6SPH84.6/70.4/80/760.82
SMA-PI2.7SPH85.7/65.2/79/750.78
RRA-RI0.65SPH79.5/59.3/74/660.78

Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value; AUROC, area under the receiver operating curve; SPH, severe portal hypertension (hepatic venous pressure gradient >12 mm Hg); HCV, hepatitis C virus; SA-RI, intraparenchymal splenic artery resistance index; SMA-PI, superior mesenteric artery-pulsatility index; RRA-RI, right interlobar renal artery resistance index.

*Damping index=minimum velocity/maximum velocity of the hepatic vein waveform.

Comparison of Diagnostic Abilities in Contrast Parameters for Grading Portal Hypertension

Contrast agentPatients, no.Parameter (cutoff value)Reliability*Grade of PHSe/Sp/PPV/NPV/Ac/PLR/NLRAUROCStudy
Sonovue71HVAT (14 s)3.7%–3.9%, 2.7%–3.2%CSPH93/87/91/90/-/6.95/0.080.973Kim et al.30
35 (v)κ=0.870.953
SonoVue53HVAT (19 s)0.938 (ICC)SPH56/89/95/35/63/-/-, R10.72Jeong et al.31
(50/89/94/32/58/-/-, R2)0.71
ITT (6 s)0.860 (ICC)SPH91/89/97/73/91/-/-, R10.94
(85/78/94/58/84/-/-, R2)0.90
Sonazoid91SA-SV§ (13.5 s)4.9% (IOV)CSPH71/68/69/70/-/-/-0.76Shimada et al.32
SA-SV (14.5 s)SPH60/80/75/67/-/-/-0.76

The three studies show the diagnostic abilities of contrast parameters based on dynamic microbubbles for clinically significant portal hypertension (CSPH) and/or severe portal hypertension (SPH). The first study reported that hepatic vein arrival time (HVAT) showed area under the receiver operating curve (AUROC) 0.975/0.953 to diagnose CSPH; the second study compared two contrast parameters, HVAT and intrahepatic transit time (ITT) to diagnose SPH and found that ITT showed higher ability with AUROC 0.90/0.94. The third study proposed splenic circulation time using Sonazoid, and the AUROC for CSPH/SPH was 0.76.

PH, portal hypertension; Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value; Ac, accuracy; PLR, positive likelihood ratio; NLR, negative likelihood ratio; CSPH, clinically significant portal hypertension (hepatic venous pressure gradient ≥10 mm Hg); ICC, intraclass correlation coefficient; SPH, severe portal hypertension (hepatic venous pressure gradient ≥12 mm Hg); SA-SV, splenic artery-splenic vein; IOV, interobserver variability.

*Reliability was presented by interobserver/intraobserver variability, κ-value, or ICC, 3.7% and 3.9% for day-to-day intraobserver variability in the HVAT measurement, 2.7% and 3.2% for IOV of the drawing and interpretation of the time-intensity curve. κ=0.87, IOV. ICC for the interpretation, 0.938 (95% confidence interval, 0.894–0.964) for HVAT and 0.860 (0.769–0.917) for ITT. 4.9% for IOV;

Validation set;

R1, reader 1 and R2, reader 2

§The interval time from the contrast onset in the splenic artery to the time to reach the maximum intensity level in the splenic vein.

Comparison of Diagnostic Abilities of Elastography for Grading Portal Hypertension

EquipmentPatient no.Parameter (cutoff value)Grade of PHSe/Sp/PPV/NPV/Ac/PLR/NLRAUROCStudy
TE61 (HCV)LS (13.6 kPa)CSPH97/92/97/92/-/13.7/0.020.99Vizzutti et al.37
LS (17.6 kPa)SPH94/81/86/91/-/4.9/0.080.92
TE44 (HCV)LS (20.5 kPa)CSPH63/70/88/35/-/-/-0.76Lemoine et al.44
48 (alcohol)LS (34.9 kPa)CSPH90/88/97/64/-/-/-0.94
TE150LS (21 kPa)CSPH90/93/93/91/-/-/-0.945Bureau et al.38
TE38 (HIV-HCV)LS (14 kPa)CSPH93/50/84/71/-/3.5/0.60.80Sánchez-Conde et al.39
LS (23 kPa)SPH83/67/79/71/-/2.5/0.50.80
TE95LS (29 kPa)CSPH72/100/100/56/-/0.30.90Kitson et al.40
TE97 (C-P A, HCC)LS (13.6 kPa)CSPH91/57/59/90/-/2.13/0.16-Llop et al.36
LS (21 kPa)CSPH53/91/81/74/-/6.24/0.51-
TE79LS (65.3 kPa)CSPH52/100/100/21/57/-/-0.78Elkrief et al.41
RT-SWELS (24.5 kPa)CSPH81/88/98/35/82/-/-0.87Elkrief et al.41
RT-SWE92LS (15.2 kPa)CSPH86/80/96/52/85/-/-0.819Kim et al.42
LS (21.6 kPa)SPH83/81/92/66/83/-/-0.867
TE124 (HCV)LS (8.74 kPa)HVPG >6 mm Hg90/81/-/-/85/-/-0.93Carrión et al.43

Table 3 summarizes the diagnostic abilities of elastography for grading portal hypertension. Transient elastography (TE) showed area under the receiver operating curve (AUROC) 0.76–0.99 for clinically significant portal hypertension (CSPH) and 0.80/0.92 for severe portal hypertension (SPH), and real-time share wave elastography (RT-SWE) showed AUROC 0.819/0.87 for CSPH and 0.867 for SPH.

PH, portal hypertension; Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value; Ac, accuracy; PLR, positive likelihood ratio; NLR, negative likelihood ratio; HCV, hepatitis C virus; LS, liver stiffness; CSPH, clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] ≥10 mm Hg); SPH, severe portal hypertension (HVPG ≥12 mm Hg); HIV, human immunodeficiency virus; C-P A, Child-Pugh A.

Diagnostic Ability of Elastography for Esophageal Varices

StudyPatient no.EtiologyPrevalence of EV (%)AUROCAccuracyCutoffSe/Sp/PPV/NPVEndpoint
Liver stiffness by TE
 Vizzutti et al.3761HCV63.70.769017.690/43/77/66Any EV
 Kazemi et al.47165Mix41.20.84-13.995/43/57/91Any EV
0.83-1991/60/48/95Large EV
 Bureau et al.38150Mix720.85NA21.184/71/-/-Any EV
Mix480.76NA29.381/61/-/-Large EV
 Castéra et al.48298HCV360.84-21.576/78/68/84Any EV
190.87-30.577/85/56/94Large EV
 Pritchett et al.77211Mix62.6 (mild)0.74-19.576/66/82/56Any EV
37.4, large0.76-19.891/56/55/91Large (vs small)
 Nguyen-Khac et al.78183Mix22.4, large0.75-4873.2/73.2/44.1/90.4Large EV
 Malik et al.79124Mix50.8 (in cirrhosis)0.85NA20-/-/80/75Any EV
Liver stiffness by ARFI
 Morishita et al.80135HCV51.10.89-2.05 m/s83/76/78/81Any EV
33.70.868-2.39 m/s81/82/69/89Large EV
Spleen stiffness
 Sharma et al.81174Mix710.8988640.8 kPa94/76/91/84Any EV
0.819-54.5 kPa76/73/-/-Bleeder
 Colecchia et al.45100HCV530.941Any EV
Spleen stiffness by ARFI
 Takuma et al.82340Mix38.80.933753.1898.5/60.1/61/98.4Any EV
0.9372.13.398.9/62.9/47.8/99.4Large EV

The diagnostic ability of liver/spleen stiffness measurement for esophageal varices (EV) is summarized. Liver stiffness measurement showed area under the receiver operating curve (AUROC) 0.74–0.89 for a presence of EV and 0.75–0.87 for large varices. Spleen stiffness measurement showed AUROC 0.898–0.941 to detect a presence of EV, which was greater than that based on liver stiffness measurement.

Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value; TE, transient elastography; HCV, hepatitis C virus; NA, not available; ARFI, acoustic radiation force impulse imaging.

Summary of Ultrasound-Based Techniques

ApplicationStrength/advantageWeakness/disadvantage
Ultrasound
 B-modeFirst line approachSimple and noninvasiveAvailable only anatomical information
 Doppler (pulsed, color, power)Flow direction and velocity measurementReal-time observationPoor detection of slow blood flow
Reduced frame rate
 ContrastSecond line approach
Focal hepatic lesions (detection, characterization, therapeutic support)
Diffuse liver disease (characterization, grading fibrosis and portal hypertension)
Increased detectability of blood flow
Kupffer imaging (Sonazoid)
Invasiveness (agent injection)
Possible adverse events
Limited availability of agents
Cost
Transient elastographyGrading fibrosis and portal hypertension
Evaluation of complication
Simple and noninvasiveNo grey-scale image
Low technical success in patients with ascites
Share wave elastographyGrading fibrosis and portal hypertension
Evaluation of complication
Simple and noninvasive
Available grey-scale image
Technical success in patients with ascites
Small number of research
References
  1. Kim, MY, Jeong, WK, and Baik, SK (2014). Invasive and non-invasive diagnosis of cirrhosis and portal hypertension. World J Gastroenterol. 20, 4300-4315.
    Pubmed KoreaMed CrossRef
  2. Tsochatzis, EA, Bosch, J, and Burroughs, AK (2014). Liver cirrhosis. Lancet. 383, 1749-1761.
    Pubmed CrossRef
  3. Maruyama, H, and Sanyal, AJ (2012). Portal hypertension: non-surgical and surgical management. Schiff’s diseases of the liver, Schiff, ER, Maddrey, WC, and Sorrell, MF, ed. Oxford: Wiley-Blackwell, pp. 326-360
  4. Baik, SK (2010). Haemodynamic evaluation by Doppler ultrasonography in patients with portal hypertension: a review. Liver Int. 30, 1403-1413.
    Pubmed CrossRef
  5. Maruyama, H, Kamezaki, H, and Kondo, T (2013). Effects of inferior mesenteric vein flow in patients with cirrhosis. Clin Gastroenterol Hepatol. 11, 1648-1654.
    Pubmed CrossRef
  6. Maruyama, H, Kondo, T, Kiyono, S, Sekimoto, T, Takahashi, M, and Yokosuka, O (2015). Influence of splenorenal shunt on long-term outcomes in cirrhosis. Scand J Gastroenterol. 50, 593-600.
    Pubmed CrossRef
  7. Sanyal, AJ, Bosch, J, Blei, A, and Arroyo, V (2008). Portal hypertension and its complications. Gastroenterology. 134, 1715-1728.
    Pubmed CrossRef
  8. Maruyama, H, and Yokosuka, O (2012). Pathophysiology of portal hypertension and esophageal varices. Int J Hepatol. 2012, 895787.
    Pubmed KoreaMed CrossRef
  9. D’Amico, G, Garcia-Tsao, G, and Pagliaro, L (2006). Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 44, 217-231.
    CrossRef
  10. Thabut, D, Moreau, R, and Lebrec, D (2011). Noninvasive assessment of portal hypertension in patients with cirrhosis. Hepatology. 53, 683-694.
    Pubmed CrossRef
  11. Maruyama, H, Shiha, G, and Yokosuka, O (2016). Non-invasive assessment of portal hypertension and liver fibrosis using contrast-enhanced ultrasonography. Hepatol Int. 10, 267-276.
    CrossRef
  12. Oberti, F, Valsesia, E, and Pilette, C (1997). Noninvasive diagnosis of hepatic fibrosis or cirrhosis. Gastroenterology. 113, 1609-1616.
    Pubmed CrossRef
  13. Colli, A, Fraquelli, M, Andreoletti, M, Marino, B, Zuccoli, E, and Conte, D (2003). Severe liver fibrosis or cirrhosis: accuracy of US for detection: analysis of 300 cases. Radiology. 227, 89-94.
    Pubmed CrossRef
  14. Maruyama, H, Kondo, T, Sekimoto, T, and Yokosuka, O (2015). Differential clinical impact of ascites in cirrhosis and idiopathic portal hypertension. Medicine (Baltimore). 94, e1056.
    CrossRef
  15. Kondo, T, Maruyama, H, and Sekimoto, T (2014). Influence of paraumbilical vein patency on the portal hemodynamics of patients with cirrhosis. J Clin Gastroenterol. 48, 178-183.
    CrossRef
  16. Maruyama, H, Kamezaki, H, Kondo, T, Sekimoto, T, Takahashi, M, and Yokosuka, O (2014). Sonographic and clinical features of collateral vessels at the splenic hilum in cirrhosis. Clin Radiol. 69, e140-e145.
    CrossRef
  17. Kondo, T, Maruyama, H, Sekimoto, T, Shimada, T, Takahashi, M, and Yokosuka, O (2015). Reversed portal flow: clinical influence on the long-term outcomes in cirrhosis. World J Gastroenterol. 21, 8894-8902.
    Pubmed KoreaMed CrossRef
  18. Sudhamshu, KC, Matsutani, S, Maruyama, H, Akiike, T, and Saisho, H (2006). Doppler study of hepatic vein in cirrhotic patients: correlation with liver dysfunction and hepatic hemodynamics. World J Gastroenterol. 12, 5853-5858.
    Pubmed KoreaMed CrossRef
  19. Kondo, T, Maruyama, H, and Sekimoto, T (2016). Impact of portal hemodynamics on Doppler ultrasonography for predicting decompensation and long-term outcomes in patients with cirrhosis. Scand J Gastroenterol. 51, 236-244.
    CrossRef
  20. Kim, MY, Baik, SK, and Park, DH (2007). Damping index of Doppler hepatic vein waveform to assess the severity of portal hypertension and response to propranolol in liver cirrhosis: a prospective non-randomized study. Liver Int. 27, 1103-1110.
    Pubmed CrossRef
  21. Vizzutti, F, Arena, U, and Rega, L (2007). Performance of Doppler ultrasound in the prediction of severe portal hypertension in hepatitis C virus-related chronic liver disease. Liver Int. 27, 1379-1388.
    Pubmed
  22. Berzigotti, A, Gilabert, R, and Abraldes, JG (2008). Noninvasive prediction of clinically significant portal hypertension and esophageal varices in patients with compensated liver cirrhosis. Am J Gastroenterol. 103, 1159-1167.
    Pubmed CrossRef
  23. Quaia, E (2007). Microbubble ultrasound contrast agents: an update. Eur Radiol. 17, 1995-2008.
    Pubmed CrossRef
  24. Bouakaz, A, and de Jong, N (2007). WFUMB Safety Symposium on Echo-Contrast Agents: nature and types of ultrasound contrast agents. Ultrasound Med Biol. 33, 187-196.
    Pubmed CrossRef
  25. Claudon, M, Dietrich, CF, and Choi, BI (2013). Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver–update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultrasound Med Biol. 39, 187-210.
    CrossRef
  26. Maruyama, H, Sekimoto, T, and Yokosuka, O (2016). Role of contrast-enhanced ultrasonography with Sonazoid for hepatocellular carcinoma: evidence from a 10-year experience. J Gastroenterol. 51, 421-433.
    CrossRef
  27. Zhang, CX, Hu, J, Hu, KW, Zhang, C, Wang, L, and Xu, JM (2011). Noninvasive analysis of portal pressure by contrast-enhanced sonography in patients with cirrhosis. J Ultrasound Med. 30, 205-211.
    Pubmed CrossRef
  28. Berzigotti, A, Nicolau, C, and Bellot, P (2011). Evaluation of regional hepatic perfusion (RHP) by contrast-enhanced ultrasound in patients with cirrhosis. J Hepatol. 55, 307-314.
    CrossRef
  29. Qu, EZ, Zhang, YC, Li, ZY, Liu, Y, and Wang, JR (2014). Contrast-enhanced sonography for quantitative assessment of portal hypertension in patients with liver cirrhosis. J Ultrasound Med. 33, 1971-1977.
    Pubmed CrossRef
  30. Kim, MY, Suk, KT, and Baik, SK (2012). Hepatic vein arrival time as assessed by contrast-enhanced ultrasonography is useful for the assessment of portal hypertension in compensated cirrhosis. Hepatology. 56, 1053-1062.
    Pubmed CrossRef
  31. Jeong, WK, Kim, TY, Sohn, JH, Kim, Y, and Kim, J (2015). Severe portal hypertension in cirrhosis: evaluation of perfusion parameters with contrast-enhanced ultrasonography. PLoS One. 10, e0121601.
    Pubmed KoreaMed CrossRef
  32. Shimada, T, Maruyama, H, Kondo, T, Sekimoto, T, Takahashi, M, and Yokosuka, O (2015). Impact of splenic circulation: non-invasive microbubble-based assessment of portal hemodynamics. Eur Radiol. 25, 812-820.
    CrossRef
  33. Dave, JK, Halldorsdottir, VG, and Eisenbrey, JR (2012). Investigating the efficacy of subharmonic aided pressure estimation for portal vein pressures and portal hypertension monitoring. Ultrasound Med Biol. 38, 1784-1798.
    Pubmed KoreaMed CrossRef
  34. Eisenbrey, JR, Dave, JK, and Halldorsdottir, VG (2013). Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology. 268, 581-588.
    Pubmed KoreaMed CrossRef
  35. Castera, L, Pinzani, M, and Bosch, J (2012). Non invasive evaluation of portal hypertension using transient elastography. J Hepatol. 56, 696-703.
    CrossRef
  36. Llop, E, Berzigotti, A, and Reig, M (2012). Assessment of portal hypertension by transient elastography in patients with compensated cirrhosis and potentially resectable liver tumors. J Hepatol. 56, 103-108.
    CrossRef
  37. Vizzutti, F, Arena, U, and Romanelli, RG (2007). Liver stiffness measurement predicts severe portal hypertension in patients with HCV-related cirrhosis. Hepatology. 45, 1290-1297.
    Pubmed CrossRef
  38. Bureau, C, Metivier, S, and Peron, JM (2008). Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease. Aliment Pharmacol Ther. 27, 1261-1268.
    Pubmed CrossRef
  39. Sánchez-Conde, M, Montes Ramírez, ML, and Bellón Cano, JM (2011). Impact of liver steatosis on the correlation between liver stiffness and fibrosis measured by transient elastography in patients coinfected with human immunodeficiency virus and hepatitis C virus. J Viral Hepat. 18, e278-e283.
    CrossRef
  40. Kitson, MT, Roberts, SK, Colman, JC, Paul, E, Button, P, and Kemp, W (2015). Liver stiffness and the prediction of clinically significant portal hypertension and portal hypertensive complications. Scand J Gastroenterol. 50, 462-469.
    Pubmed CrossRef
  41. Elkrief, L, Rautou, PE, and Ronot, M (2015). Prospective comparison of spleen and liver stiffness by using shear-wave and transient elastography for detection of portal hypertension in cirrhosis. Radiology. 275, 589-598.
    CrossRef
  42. Kim, TY, Jeong, WK, Sohn, JH, Kim, J, Kim, MY, and Kim, Y (2015). Evaluation of portal hypertension by real-time shear wave elastography in cirrhotic patients. Liver Int. 35, 2416-2424.
    Pubmed CrossRef
  43. Carrión, JA, Navasa, M, Bosch, J, Bruguera, M, Gilabert, R, and Forns, X (2006). Transient elastography for diagnosis of advanced fibrosis and portal hypertension in patients with hepatitis C recurrence after liver transplantation. Liver Transpl. 12, 1791-1798.
    Pubmed CrossRef
  44. Lemoine, M, Katsahian, S, and Ziol, M (2008). Liver stiffness measurement as a predictive tool of clinically significant portal hypertension in patients with compensated hepatitis C virus or alcohol-related cirrhosis. Aliment Pharmacol Ther. 28, 1102-1110.
    Pubmed CrossRef
  45. Colecchia, A, Montrone, L, and Scaioli, E (2012). Measurement of spleen stiffness to evaluate portal hypertension and the presence of esophageal varices in patients with HCV-related cirrhosis. Gastroenterology. 143, 646-654.
    Pubmed CrossRef
  46. Mueller, S, and Sandrin, L (2010). Liver stiffness: a novel parameter for the diagnosis of liver disease. Hepat Med. 2, 49-67.
    Pubmed KoreaMed CrossRef
  47. Kazemi, F, Kettaneh, A, and N’kontchou, G (2006). Liver stiffness measurement selects patients with cirrhosis at risk of bearing large oesophageal varices. J Hepatol. 45, 230-235.
    Pubmed CrossRef
  48. Castéra, L, Le Bail, B, and Roudot-Thoraval, F (2009). Early detection in routine clinical practice of cirrhosis and oesophageal varices in chronic hepatitis C: comparison of transient elastography (FibroScan) with standard laboratory tests and non-invasive scores. J Hepatol. 50, 59-68.
    CrossRef
  49. Shi, KQ, Fan, YC, and Pan, ZZ (2013). Transient elastography: a meta-analysis of diagnostic accuracy in evaluation of portal hypertension in chronic liver disease. Liver Int. 33, 62-71.
    CrossRef
  50. Robic, MA, Procopet, B, and Métivier, S (2011). Liver stiffness accurately predicts portal hypertension related complications in patients with chronic liver disease: a prospective study. J Hepatol. 55, 1017-1024.
    Pubmed CrossRef
  51. Sekimoto, T, Maruyama, H, and Kiyono, S (2015). Liver stiffness: a significant relationship with the waveform pattern in the hepatic vein. Ultrasound Med Biol. 41, 1801-1807.
    Pubmed CrossRef
  52. Berzigotti, A, Seijo, S, and Arena, U (2013). Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology. 144, 102-111.e1.
    CrossRef
  53. Ding, NS, Nguyen, T, and Iser, DM (2016). Liver stiffness plus platelet count can be used to exclude high-risk oesophageal varices. Liver Int. 36, 240-245.
    CrossRef
  54. Cho, EJ, Kim, MY, and Lee, JH (2015). Diagnostic and prognostic values of noninvasive predictors of portal hypertension in patients with alcoholic cirrhosis. PLoS One. 10, e0133935.
    Pubmed KoreaMed CrossRef
  55. Procopet, B, Cristea, VM, and Robic, MA (2015). Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension. Dig Liver Dis. 47, 411-416.
    Pubmed CrossRef
  56. Ziol, M, Handra-Luca, A, and Kettaneh, A (2005). Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 41, 48-54.
    Pubmed CrossRef
  57. Castéra, L, Vergniol, J, and Foucher, J (2005). Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 128, 343-350.
    Pubmed CrossRef
  58. Fraquelli, M, Rigamonti, C, and Casazza, G (2007). Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease. Gut. 56, 968-973.
    Pubmed KoreaMed CrossRef
  59. Roulot, D, Czernichow, S, Le Clésiau, H, Costes, JL, Vergnaud, AC, and Beaugrand, M (2008). Liver stiffness values in apparently healthy subjects: influence of gender and metabolic syndrome. J Hepatol. 48, 606-613.
    Pubmed CrossRef
  60. Coco, B, Oliveri, F, and Maina, AM (2007). Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases. J Viral Hepat. 14, 360-369.
    Pubmed CrossRef
  61. Chan, HL, Wong, GL, and Choi, PC (2009). Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B. J Viral Hepat. 16, 36-44.
    CrossRef
  62. Lupşor, M, Badea, R, and Stefănescu, H (2008). Analysis of histopathological changes that influence liver stiffness in chronic hepatitis C: results from a cohort of 324 patients. J Gastrointestin Liver Dis. 17, 155-163.
  63. Arena, U, Vizzutti, F, and Abraldes, JG (2008). Reliability of transient elastography for the diagnosis of advanced fibrosis in chronic hepatitis C. Gut. 57, 1288-1293.
    Pubmed CrossRef
  64. Millonig, G, Reimann, FM, and Friedrich, S (2008). Extrahepatic cholestasis increases liver stiffness (FibroScan) irrespective of fibrosis. Hepatology. 48, 1718-1723.
    Pubmed CrossRef
  65. Harata, M, Hashimoto, S, and Kawabe, N (2011). Liver stiffness in extrahepatic cholestasis correlates positively with bilirubin and negatively with alanine aminotransferase. Hepatol Res. 41, 423-429.
    Pubmed CrossRef
  66. Lupsor, M, Badea, R, and Stefanescu, H (2010). Performance of unidimensional transient elastography in staging non-alcoholic steatohepatitis. J Gastrointestin Liver Dis. 19, 53-60.
    Pubmed
  67. Boursier, J, de Ledinghen, V, and Sturm, N (2014). Precise evaluation of liver histology by computerized morphometry shows that steatosis influences liver stiffness measured by transient elastography in chronic hepatitis C. J Gastroenterol. 49, 527-537.
    CrossRef
  68. Das, K, Sarkar, R, and Ahmed, SM (2012). “Normal” liver stiffness measure (LSM) values are higher in both lean and obese individuals: a population-based study from a developing country. Hepatology. 55, 584-593.
    CrossRef
  69. Myers, RP, Crotty, P, Pomier-Layrargues, G, Ma, M, Urbanski, SJ, and Elkashab, M (2010). Prevalence, risk factors and causes of discordance in fibrosis staging by transient elastography and liver biopsy. Liver Int. 30, 1471-1480.
    Pubmed CrossRef
  70. Berzigotti, A, De Gottardi, A, and Vukotic, R (2013). Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension. PLoS One. 8, e58742.
    Pubmed KoreaMed CrossRef
  71. Arena, U, Lupsor Platon, M, and Stasi, C (2013). Liver stiffness is influenced by a standardized meal in patients with chronic hepatitis C virus at different stages of fibrotic evolution. Hepatology. 58, 65-72.
    Pubmed CrossRef
  72. Millonig, G, Friedrich, S, and Adolf, S (2010). Liver stiffness is directly influenced by central venous pressure. J Hepatol. 52, 206-210.
    CrossRef
  73. Castéra, L, Foucher, J, and Bernard, PH (2010). Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology. 51, 828-835.
    Pubmed
  74. Sirli, R, Sporea, I, Bota, S, and Jurchiş, A (2013). Factors influencing reliability of liver stiffness measurements using transient elastography (M-probe)-monocentric experience. Eur J Radiol. 82, e313-e316.
    Pubmed CrossRef
  75. Lucidarme, D, Foucher, J, and Le Bail, B (2009). Factors of accuracy of transient elastography (fibroscan) for the diagnosis of liver fibrosis in chronic hepatitis C. Hepatology. 49, 1083-1089.
    Pubmed CrossRef
  76. Boursier, J, Zarski, JP, and de Ledinghen, V (2013). Determination of reliability criteria for liver stiffness evaluation by transient elastography. Hepatology. 57, 1182-1191.
    CrossRef
  77. Pritchett, S, Cardenas, A, Manning, D, Curry, M, and Afdhal, NH (2011). The optimal cut-off for predicting large oesophageal varices using transient elastography is disease specific. J Viral Hepat. 18, e75-e80.
    CrossRef
  78. Nguyen-Khac, E, Saint-Leger, P, Tramier, B, Coevoet, H, Capron, D, and Dupas, JL (2010). Noninvasive diagnosis of large esophageal varices by Fibroscan: strong influence of the cirrhosis etiology. Alcohol Clin Exp Res. 34, 1146-1153.
    Pubmed
  79. Malik, R, Lai, M, and Sadiq, A (2010). Comparison of transient elastography, serum markers and clinical signs for the diagnosis of compensated cirrhosis. J Gastroenterol Hepatol. 25, 1562-1568.
    Pubmed CrossRef
  80. Morishita, N, Hiramatsu, N, and Oze, T (2014). Liver stiffness measurement by acoustic radiation force impulse is useful in predicting the presence of esophageal varices or high-risk esophageal varices among patients with HCV-related cirrhosis. J Gastroenterol. 49, 1175-1182.
    CrossRef
  81. Sharma, P, Kirnake, V, and Tyagi, P (2013). Spleen stiffness in patients with cirrhosis in predicting esophageal varices. Am J Gastroenterol. 108, 1101-1107.
    Pubmed CrossRef
  82. Takuma, Y, Nouso, K, and Morimoto, Y (2013). Measurement of spleen stiffness by acoustic radiation force impulse imaging identifies cirrhotic patients with esophageal varices. Gastroenterology. 144, 92-101.e2.
    CrossRef
  83. Schwabl, P, Bota, S, and Salzl, P (2015). New reliability criteria for transient elastography increase the number of accurate measurements for screening of cirrhosis and portal hypertension. Liver Int. 35, 381-390.
    CrossRef
  84. Han, JY, Cho, JH, Kwon, HJ, and Nam, KJ (2012). Predicting portal hypertension as assessed by acoustic radiation force impulse: correlations with the Doppler ultrasound. Br J Radiol. 85, e404-e409.
    Pubmed KoreaMed CrossRef
  85. Vermehren, J, Polta, A, and Zimmermann, O (2012). Comparison of acoustic radiation force impulse imaging with transient elastography for the detection of complications in patients with cirrhosis. Liver Int. 32, 852-858.
    Pubmed CrossRef
  86. Choi, SY, Jeong, WK, Kim, Y, Kim, J, Kim, TY, and Sohn, JH (2014). Shear-wave elastography: a noninvasive tool for monitoring changing hepatic venous pressure gradients in patients with cirrhosis. Radiology. 273, 917-926.
    Pubmed CrossRef
  87. Procopet, B, Berzigotti, A, and Abraldes, JG (2015). Real-time shear-wave elastography: applicability, reliability and accuracy for clinically significant portal hypertension. J Hepatol. 62, 1068-1075.
    CrossRef
  88. Chin, JL, Chan, G, Ryan, JD, and McCormick, PA (2015). Spleen stiffness can non-invasively assess resolution of portal hypertension after liver transplantation. Liver Int. 35, 518-523.
    CrossRef
  89. Bota, S, Sporea, I, and Sirli, R (2012). Can ARFI elastography predict the presence of significant esophageal varices in newly diagnosed cirrhotic patients?. Ann Hepatol. 11, 519-525.
    Pubmed
Tables

Diagnostic Ability of Doppler Parameters

StudyPatients, no.EtiologyParameterCutoff valueDiagnosisSe/Sp/PPV/NPVAUROC
Kondo et al.19236MixVelocity12.8 cm/sDecompensation68/75/68/750.7395
Flow directionReversePrognosis21.8/99.3/70.6/60.6-
Kim et al.2076MixDamping index*0.6SPH75.9/81.8/91.1/58.10.860
Vizzutti et al.2166HCVSA-RI0.6SPH84.6/70.4/80/760.82
SMA-PI2.7SPH85.7/65.2/79/750.78
RRA-RI0.65SPH79.5/59.3/74/660.78

Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value; AUROC, area under the receiver operating curve; SPH, severe portal hypertension (hepatic venous pressure gradient >12 mm Hg); HCV, hepatitis C virus; SA-RI, intraparenchymal splenic artery resistance index; SMA-PI, superior mesenteric artery-pulsatility index; RRA-RI, right interlobar renal artery resistance index.

Damping index=minimum velocity/maximum velocity of the hepatic vein waveform.

Comparison of Diagnostic Abilities in Contrast Parameters for Grading Portal Hypertension

Contrast agentPatients, no.Parameter (cutoff value)Reliability*Grade of PHSe/Sp/PPV/NPV/Ac/PLR/NLRAUROCStudy
Sonovue71HVAT (14 s)3.7%–3.9%, 2.7%–3.2%CSPH93/87/91/90/-/6.95/0.080.973Kim et al.30
35 (v)κ=0.870.953
SonoVue53HVAT (19 s)0.938 (ICC)SPH56/89/95/35/63/-/-, R10.72Jeong et al.31
(50/89/94/32/58/-/-, R2)0.71
ITT (6 s)0.860 (ICC)SPH91/89/97/73/91/-/-, R10.94
(85/78/94/58/84/-/-, R2)0.90
Sonazoid91SA-SV§ (13.5 s)4.9% (IOV)CSPH71/68/69/70/-/-/-0.76Shimada et al.32
SA-SV (14.5 s)SPH60/80/75/67/-/-/-0.76

The three studies show the diagnostic abilities of contrast parameters based on dynamic microbubbles for clinically significant portal hypertension (CSPH) and/or severe portal hypertension (SPH). The first study reported that hepatic vein arrival time (HVAT) showed area under the receiver operating curve (AUROC) 0.975/0.953 to diagnose CSPH; the second study compared two contrast parameters, HVAT and intrahepatic transit time (ITT) to diagnose SPH and found that ITT showed higher ability with AUROC 0.90/0.94. The third study proposed splenic circulation time using Sonazoid, and the AUROC for CSPH/SPH was 0.76.

PH, portal hypertension; Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value; Ac, accuracy; PLR, positive likelihood ratio; NLR, negative likelihood ratio; CSPH, clinically significant portal hypertension (hepatic venous pressure gradient ≥10 mm Hg); ICC, intraclass correlation coefficient; SPH, severe portal hypertension (hepatic venous pressure gradient ≥12 mm Hg); SA-SV, splenic artery-splenic vein; IOV, interobserver variability.

Reliability was presented by interobserver/intraobserver variability, κ-value, or ICC, 3.7% and 3.9% for day-to-day intraobserver variability in the HVAT measurement, 2.7% and 3.2% for IOV of the drawing and interpretation of the time-intensity curve. κ=0.87, IOV. ICC for the interpretation, 0.938 (95% confidence interval, 0.894–0.964) for HVAT and 0.860 (0.769–0.917) for ITT. 4.9% for IOV;

Validation set;

R1, reader 1 and R2, reader 2

The interval time from the contrast onset in the splenic artery to the time to reach the maximum intensity level in the splenic vein.

Comparison of Diagnostic Abilities of Elastography for Grading Portal Hypertension

EquipmentPatient no.Parameter (cutoff value)Grade of PHSe/Sp/PPV/NPV/Ac/PLR/NLRAUROCStudy
TE61 (HCV)LS (13.6 kPa)CSPH97/92/97/92/-/13.7/0.020.99Vizzutti et al.37
LS (17.6 kPa)SPH94/81/86/91/-/4.9/0.080.92
TE44 (HCV)LS (20.5 kPa)CSPH63/70/88/35/-/-/-0.76Lemoine et al.44
48 (alcohol)LS (34.9 kPa)CSPH90/88/97/64/-/-/-0.94
TE150LS (21 kPa)CSPH90/93/93/91/-/-/-0.945Bureau et al.38
TE38 (HIV-HCV)LS (14 kPa)CSPH93/50/84/71/-/3.5/0.60.80Sánchez-Conde et al.39
LS (23 kPa)SPH83/67/79/71/-/2.5/0.50.80
TE95LS (29 kPa)CSPH72/100/100/56/-/0.30.90Kitson et al.40
TE97 (C-P A, HCC)LS (13.6 kPa)CSPH91/57/59/90/-/2.13/0.16-Llop et al.36
LS (21 kPa)CSPH53/91/81/74/-/6.24/0.51-
TE79LS (65.3 kPa)CSPH52/100/100/21/57/-/-0.78Elkrief et al.41
RT-SWELS (24.5 kPa)CSPH81/88/98/35/82/-/-0.87Elkrief et al.41
RT-SWE92LS (15.2 kPa)CSPH86/80/96/52/85/-/-0.819Kim et al.42
LS (21.6 kPa)SPH83/81/92/66/83/-/-0.867
TE124 (HCV)LS (8.74 kPa)HVPG >6 mm Hg90/81/-/-/85/-/-0.93Carrión et al.43

Table 3 summarizes the diagnostic abilities of elastography for grading portal hypertension. Transient elastography (TE) showed area under the receiver operating curve (AUROC) 0.76–0.99 for clinically significant portal hypertension (CSPH) and 0.80/0.92 for severe portal hypertension (SPH), and real-time share wave elastography (RT-SWE) showed AUROC 0.819/0.87 for CSPH and 0.867 for SPH.

PH, portal hypertension; Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value; Ac, accuracy; PLR, positive likelihood ratio; NLR, negative likelihood ratio; HCV, hepatitis C virus; LS, liver stiffness; CSPH, clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] ≥10 mm Hg); SPH, severe portal hypertension (HVPG ≥12 mm Hg); HIV, human immunodeficiency virus; C-P A, Child-Pugh A.

Diagnostic Ability of Elastography for Esophageal Varices

StudyPatient no.EtiologyPrevalence of EV (%)AUROCAccuracyCutoffSe/Sp/PPV/NPVEndpoint
Liver stiffness by TE
 Vizzutti et al.3761HCV63.70.769017.690/43/77/66Any EV
 Kazemi et al.47165Mix41.20.84-13.995/43/57/91Any EV
0.83-1991/60/48/95Large EV
 Bureau et al.38150Mix720.85NA21.184/71/-/-Any EV
Mix480.76NA29.381/61/-/-Large EV
 Castéra et al.48298HCV360.84-21.576/78/68/84Any EV
190.87-30.577/85/56/94Large EV
 Pritchett et al.77211Mix62.6 (mild)0.74-19.576/66/82/56Any EV
37.4, large0.76-19.891/56/55/91Large (vs small)
 Nguyen-Khac et al.78183Mix22.4, large0.75-4873.2/73.2/44.1/90.4Large EV
 Malik et al.79124Mix50.8 (in cirrhosis)0.85NA20-/-/80/75Any EV
Liver stiffness by ARFI
 Morishita et al.80135HCV51.10.89-2.05 m/s83/76/78/81Any EV
33.70.868-2.39 m/s81/82/69/89Large EV
Spleen stiffness
 Sharma et al.81174Mix710.8988640.8 kPa94/76/91/84Any EV
0.819-54.5 kPa76/73/-/-Bleeder
 Colecchia et al.45100HCV530.941Any EV
Spleen stiffness by ARFI
 Takuma et al.82340Mix38.80.933753.1898.5/60.1/61/98.4Any EV
0.9372.13.398.9/62.9/47.8/99.4Large EV

The diagnostic ability of liver/spleen stiffness measurement for esophageal varices (EV) is summarized. Liver stiffness measurement showed area under the receiver operating curve (AUROC) 0.74–0.89 for a presence of EV and 0.75–0.87 for large varices. Spleen stiffness measurement showed AUROC 0.898–0.941 to detect a presence of EV, which was greater than that based on liver stiffness measurement.

Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value; TE, transient elastography; HCV, hepatitis C virus; NA, not available; ARFI, acoustic radiation force impulse imaging.

Summary of Ultrasound-Based Techniques

ApplicationStrength/advantageWeakness/disadvantage
Ultrasound
 B-modeFirst line approachSimple and noninvasiveAvailable only anatomical information
 Doppler (pulsed, color, power)Flow direction and velocity measurementReal-time observationPoor detection of slow blood flow
Reduced frame rate
 ContrastSecond line approach
Focal hepatic lesions (detection, characterization, therapeutic support)
Diffuse liver disease (characterization, grading fibrosis and portal hypertension)
Increased detectability of blood flow
Kupffer imaging (Sonazoid)
Invasiveness (agent injection)
Possible adverse events
Limited availability of agents
Cost
Transient elastographyGrading fibrosis and portal hypertension
Evaluation of complication
Simple and noninvasiveNo grey-scale image
Low technical success in patients with ascites
Share wave elastographyGrading fibrosis and portal hypertension
Evaluation of complication
Simple and noninvasive
Available grey-scale image
Technical success in patients with ascites
Small number of research
Figures
Fig. 1. Pulsed Doppler image for portal trunk (68-year-old male, non-B, non-C cirrhosis). The portal trunk was demonstrated as a longitudinal view and sample volume was used with the optimal width to include the vessel. Time-averaged mean flow velocity was obtained from the waveform of the Doppler signal with the beam-vessel angle, which was 60 degrees or smaller. Flow volume was calculated by multiplying mean flow velocity by automatic cross-section of the vessel every 60 seconds.
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