Hemodynamic Evaluation of Portal Hypertension

REVIEW ARTICLE

Haemodynamic evaluation byDoppler ultrasonography in patientswithportal hypertension: a reviewSoon Koo Baik

Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea

Keywords

Doppler ultrasonography – haemodynamics –

portal hypertension

Abbreviations:

CD EUS, colour Doppler endoscopic

ultrasonography; DI, damping index; HV,

hepatic vein waveform; HVPG, hepatic

venous pressure gradient; HVTT, hepatic vein

transit time; IHCT, intrahepatic circulatory

time; PI, pulsatility index; PVV, portal vein

velocity; RI, resistive index; US,

ultrasonography.

Correspondence

Dr Soon Koo Baik, Department of Internal

Medicine, Yonsei University, Wonju College of

Medicine, 162, Ilsan-dong, Wonju, Korea

Tel: 182 33 741 1223

Fax: 182 33 741 1228

e-mail: [email protected]

Received 24 February 2010

Accepted 21 July 2010

DOI:10.1111/j.1478-3231.2010.02326.x

AbstractDoppler ultrasonography (US) has an advantage of being non-invasive;therefore, several attempts have been made to investigate the haemodynamicalterations in cirrhosis and the response to medical treatment of portalhypertension. Doppler indices, which have been commonly used for theevaluation of portal hypertension, include the measurement of portal andsplenic venous blood velocity and flows, and the resistive and pulsatility indexat hepatic, splenic, renal, superior mesenteric artery. Although many positiveevidences have been suggested, its clinical usefulness in portal hypertensionremains unsettled because of being plagued by lack of reproducibility andaccuracy characterized by intra- and interobserver variation. However, re-cently, Doppler’s usefulness in assessment of severity of portal hypertension interms of reproducibility, technical ease and accuracy and response to drugsthat reduce the portal pressure has been proposed. In addition, because mostof the patients with cirrhosis and portal hypertension have intrahepaticshunts, they show a decrease in intrahepatic circulatory time (IHCT). DopplerUS using microbubble contrast agents allows measurement of IHCT. There-fore, application of contrast-enhanced Doppler US can be prospective for theassessment of the severity of portal hypertension. Several reports havedemonstrated that colour Doppler endoscopic US enable haemodynamicstudy to assess the portal hypertension and has a role of guidance to measurethe imaging-based variceal pressure. We have reviewed briefly the clinicalusefulness of Doppler US in assessing the severity of portal hypertension andits response to treatment.

Portal hypertension leads to serious complications suchas variceal bleeding and is responsible for significantmorbidity and mortality in patients with cirrhosis(1–5). Precise assessment of the severity of portal hyper-tension will be very useful in the management of patientswith portal hypertension and cirrhosis. Even thoughmeasurement of the hepatic venous pressure gradient(HVPG) has been accepted as the gold standard forassessing the degree of portal hypertension, because ofits invasiveness, it is not suitable for widespread routineclinical use (6–8). Doppler ultrasonography (US) allowsus to examine haemodynamics of abdominal vesselsincluding the hepatic and portal system. Thus, manyinvestigators have attempted to confirm the usefulness ofDoppler US in assessing portal hypertension in patientswith cirrhosis. In particular, it would be highly desirableto have any Doppler parameter be a suitable substitutefor the invasive current gold standard of measuringHVPG for assessing portal hypertension (7–10). How-ever, previous reports on the usefulness of Doppler USfor assessing portal hypertension showed conflicting

results in patients with cirrhosis (8–15). Recently, favour-able results of Doppler US examination focusing onhepatic vein (HV) have been demonstrated (7, 16).Furthermore, there is a high hope of utilizing DopplerUS using microbubble contrast agents to assess theseverity of portal hypertension as well as to diagnosecirrhosis (17, 18).

The purpose of this article is to review the clinicalusefulness of haemodynamic evaluation by Doppler USfocusing on novel and conventional techniques throughrecently published data for Doppler US in portal hyper-tension.

Measurements of Doppler ultrasound indices forportal haemodynamics

Blood velocity and flow

Doppler examinations allow the measurement of bloodvelocity and flow in vessel. This method is simple andconfers technical ease that its clinical application inportal hypertension has been attempted. During the

Liver International (2010)c� 2010 John Wiley & Sons A/S 1403

Liver International ISSN 1478-3223

mailto:[email protected]

measurement of velocity, the angle between the Dopplerbeam and the long axis of vessel should be o 601 foraccuracy (19–21). Applications of measuring blood velo-city and flow are almost always possible at portal andsplenic veins; however at the artery, it is impossible,except at the superior mesenteric artery. To obtain portalvein velocity (PVV) and flow, the portal vein is imagedlongitudinally in the supine position, and the Dopplersample volume is set at its crossing point with the hepaticartery. When the sample point is adjusted to the centre ofthe portal vein, the PVV is recorded in a suspendedexpiration and is averaged over a few seconds (Fig. 1).Portal venous flow is determined by the formula, cross-sectional area�mean velocity� 60 (19–22). The meanPVV in cirrhotic patients is relatively low compared withthat in healthy subjects because of increased intrahepaticvascular resistance (outflow resistance). Zironi and col-leagues reported that the mean velocity of portal vein incirrhosis and normal subjects were 13.0� 3.2 vs.19.6� 2.6 cm/s respectively. The cut-off value of 15 cm/sshowed a sensitivity and specificity of 88 and 96%,respectively (23). However, as portal hypertensive pa-tients with cirrhosis have various portosystemic shunts,some show a high level of PVV similar to normalsubjects. Indeed, we previously found that there was nosignificant correlation between PVV and HVPG (8). Inother words, portal blood velocity and flow may differbetween patients with similar portal pressures because ofsignificant variability in portosystemic collateral pat-terns. This notion is supported by the study of Merkeland colleagues, who examined the correlation between

HVPG and portal venous flow and velocity in 39cirrhotic patients, in which no significant correlationwas found (9). Variabilities in PVV measurement includeequipment-related, intra- and interobserver variance.Acceptable levels, o 8–10%, of intra- and interobservervariability have been reported previously (24–28). A co-operative training programme may reduce the intra- andinterobserver variability in PVV measurement (29).

The velocity and cross-sectional area of splenic veinare measured at the splenic hilum.

Both splenic venous velocity and flow increase inportal hypertensive patients associated with dilated sple-nic vein and enlarged spleen (Fig. 2). It has been reportedthat the splenic venous flow exceeding portal venous flowis related to the formation of portosystemic varices and ahigh risk of variceal bleeding (30).

Measurement of blood velocity and flow by DopplerUS is useful for the evaluation of patency of stent aftertransjugular intrahepatic shunt (TIPS). Patent shunts arecharacterized by stent velocity in excess of 70 cm/s andhepatofugal flow in portal circulation distal to shunt withthe presence of cardiac pulsatility (31, 32). It is knownthat stent velocity between 50 and 60 cm/s is all that isrequired to diagnose shunt stenosis (33–36).

Resistance by measuring resistive and pulsatility index

Regardless of the incidence angle, the resistances in thehepatic, splenic and renal artery can be evaluated bymeasuring the resistive index (RI) and pulsatility index(PI) if the vessel is identified by colour Doppler (8, 11, 14,

Fig. 1. Measurement of the portal venous velocity. Doppler ultrasonography shows that the portal venous velocity measured at the crossingpoint of portal vein with hepatic artery is 10.7 cm/s in a patient with cirrhosis.

Liver International (2010)1404 c� 2010 John Wiley & Sons A/S

Haemodynamic evaluation by Doppler ultrasonography Baik

37). For measuring RI and PI of the hepatic artery, underthe right intercostal scanning of the liver, the branch ofthe hepatic artery around the portal hilus is identifiedusing colour Doppler. After the Doppler sample volumeis located in the branch of the hepatic artery, the time–velocity wave of the Doppler signal is recorded (Fig. 3).The peak systolic velocity, the end diastolic velocityand the mean velocity are measured. From these mea-surements, the hepatic RI [(peak systolic velocity� enddiastolic velocity)/peak systolic velocity] and the hepaticPI [(peak systolic velocity� end diastolic velocity)/meanvelocity] are determined (8, 14, 37) (Fig. 4). With higherarterial resistance, there is increase in the peak systolicvelocity and a decrease in the peak diastolic velocity.Therefore, RI and PI increase with higher arterial resis-tance (38–40). PI is different from RI in that it uses meanvelocity as its denominator instead of the peak velocitylike RI. PI is superior to RI when arterial resistance isextremely high that the end diastolic velocity is close to0 (8). Colour Doppler allows the identification of themain branches of the splenic artery at the splenic hilus.The time–velocity wave is recorded after the Dopplersample volume is placed inside these vessels and the RIand PI are determined using the same method used forthe hepatic artery (11, 19). Similarly, the RI and PI of therenal artery are determined at the interlobar artery of thekidney (5, 38). It has been reported that the splenic RIand the hepatic PI increase parallel to the increase in theHVPG, that is, a Doppler ultrasonic determination ofthese indices may contribute to a non-invasive evaluation

of portal hypertension (11, 37). However, other studieshave reported that the RI of the hepatic artery did notcorrelate with portal hypertension (8, 13, 14). Eventhough the kidney is an extrahepatic organ, measure-ment of RI and PI in kidney can be useful in the diagnosisof portal hypertension and cirrhosis. Renal RI and PI areincreased in patients with portal hypertension and cir-rhosis, specifically those in advanced states, because renalvasoconstriction is modulated by a decrease in effectivecirculatory volume and increase in sympathetic tone incirrhosis (Fig. 5) (5, 38–40).

In terms of measuring the RI and PI, which is knownto have an advantage in measuring the vascular resistanceregardless of the incidence angle, acquiring the samearterial branch by colour Doppler in each patient isdifficult. Therefore, it is difficult to evaluate the RI andPI under the same conditions for the enrolled patients.Hence, the accuracy and reproducibility of arterial RI andPIs have been questioned (8, 41).

Hepatic vein waveform analysis

The Doppler HV waveform in healthy subjects is tripha-sic (two negative waves and one positive), and thispattern is the consequence of variations in the centralvenous pressure because of the cardiac cycle. In patientswith cirrhosis, the presence of abnormal biphasic ormonophasic HV waveforms has been incontrovertiblydemonstrated by a number of studies (7, 42–44).In addition, previous work has shown that the

Fig. 2. Splenic venous velocity and flow. Doppler ultrasonography shows that velocity of splenic vein in the splenic hilum is 16.1 cm/s, and flowis calculated as 1486.3 ml/min in a patient with cirrhosis.


Baik Haemodynamic evaluation by Doppler ultrasonography

monophasic waveform is correlated with higher Child–Pugh scores and decreased survival rates (45). ForDoppler HV examination, HV can be easily visualizedalong its longitudinal axis by colour flow mapping at thesupine position. The flow in HV displays the blue colourin colour flow mapping because it is away from theultrasonic probe. Thereafter, Doppler shift signals areobtained from the hepatic vein at a distance of 3–6 cmfrom the junction of the vein with the inferior vena cava(Fig. 6). To determine whether HV waveform analysismight be useful in the assessment of portal hypertension,Baik et al. (7) prospectively examined the relationship

between waveforms and the severity of portal hyperten-sion measured by HVPG in 78 cirrhotic patients whoexperienced variceal bleeding. A correlation was foundbetween abnormalities in HV waveforms and HVPG,i.e. with increasing HVPG, the HV waveform tendedto flatten. Furthermore, the monophasic waveformwas associated with severe portal hypertension (HVPG4 15 mmHg) with relatively high sensitivity and specifi-city in that study population. Hence, flattening of the HVwaveform observed in the cirrhotic patients indicates ahigh likelihood of severe portal hypertension. In addition,the change in the HV waveform following vasoactive agent

Fig. 4. Measurement of resistive and pulsaltility index. Resistive index = [(peak systolic velocity – end diastolic velocity)/peak systolic velocity].Pulsatility index = [(peak systolic velocity – end diastolic velocity)/mean velocity].

Fig. 3. Hepatic arterial resistance. Under the right intercostal scanning of the liver, the branch of the hepatic artery around the portal hilus isidentified using colour Doppler. After the Doppler sample volume is located in the branch of the hepatic artery, the time–velocity wave of theDoppler signal is recorded.



administration, which reduces the portal pressure, alsosignificantly correlated with that of HVPG.

Although the above HV waveform analysis is useful,evaluation with lack of a quantitative value reduces theclinical value in the assessment of portal hypertensionand in response to drug treatment. In this view, assess-ment of damping index (DI) allows the quantification ofthe extent of the abnormal HV waveform (loss ofpulsatility).

Kim and colleagues prospectively evaluated the corre-lation between the extent of abnormal Doppler HVwaveforms, expressed as DI, and the HVPG, and re-sponse to propranolol in patients with cirrhosis. DI iscalculated by dividing the minimum velocity over themaximum velocity of the HV waveform (Fig. 7) (16).Abnormal HV waveforms were seen in 66 out of 76patients (86.8%). DI significantly correlated with the

grade of HVPG, i.e. with higher HVPG, an increase inDI was observed (Po 0.01). By logistic regression analy-sis, DI4 0.6 was significantly more likely to be severeportal hypertension (odds ratio: 14.19, 95% CI:4.07–49.55). The ROC curve according to the value of0.6 of DI showed a sensitivity of 75.9% and a specificityof 81.8% for the presence of severe portal hypertension.The positive and negative predictive values according to aDI of 0.6 were 91.1 and 58.1% respectively.

Regarding the evaluation of response to drug, changeof DI following propranolol treatment also significantlycorrelated with that of HVPG (Po 0.01) (Fig. 8). In theresponder group, which showed a decrease in HVPG ofmore than 20% compared with baseline or a decrease invalue to below 12 mmHg after propranolol treatment,the mean decreased value of DI was 0.23, correspondingto a 33.6% reduction from baseline. Hence, these resultssuggest that the evaluation of Doppler HV waveformcould be a valuable supplementary tool to assess thetherapeutic response to vasoactive drugs used to treatportal hypertension, when HVPG measurement is un-feasible or unavailable.

The exact cause of these changes in the Dopplerhepatic vein waveform remains unclear. Some investiga-tors have suggested that the hepatic vein wall is thin andsurrounded by liver parenchyma, and so its compliancecan be easily reduced by parenchymal fibrosis and fatinfiltration (44, 45). However, our vasoactive agent-induced improvement in the waveforms suggests that ahaemodynamic effect of high portal pressure, rather thana fixed structural abnormality, is the pathogenic mechan-ism responsible for the abnormal waveforms (7, 16). It issupported by a recent preliminary study that reports thatabnormal HV waveform in cirrhotic patients is asso-ciated with earlier hepatic vein transit time using micro-bubble contrast agents, which means the presence ofintrahepatic shunts (17). In other words, flattening ofthe HV wave can be attributed to an increase in HVinflow from intrahepatic shunts implicated in portalhypertension, which results in haemodynamically blunt-ing the effect of variations in central venous pressureduring the cardiac cycle, rather than lack of liver

Fig. 5. Renal arterial resistance. In a Child–Pugh class A cirrhotic patient, Doppler ultrasonography shows a pulsatility index of 0.78 (a),whereas it shows a pulsatility index of 2.48 in a Child–Pugh class C cirrhotic patient (b).

Fig. 6. Classification of Doppler hepatic vein waveform withschematic drawing.



compliance. Alterations of haemodynamic parameters inportal hypertension with cirrhosis found on Doppler USare summarized in Table 1.

Colour Doppler endoscopic ultrasound

Colour Doppler endoscopic ultrasound (CD EUS) canprovide significant information regarding haemody-namics as well as morphological change in varix. Mor-phological and haemodynamic changes of the azygosvein and the left gastric vein occur in patients with portalhypertension. Haemodynamic study and visualization of

the azygos vein and the left gastric vein can be performedwell with CD EUS to assess portal hypertension. It has beensuggested that a higher hepatofugal flow of the left gastricvein with CD EUS is associated with the development ofoesophageal varix (46). Maximal blood velocity of theazygos vein is increased in patients with portal hyperten-sion. Azygos vein flow has been found to be four to sixtimes higher in patients with portal hypertension andcirrhosis than in normal subjects and is directly related topressure in the portal system. CD EUS is also useful inassessing azygos blood flow and in monitoring the effect ofvasoactive agents in portal hypertension (47).

Fig. 7. Measurement of damping index (DI) of the hepatic vein waveform. DI is calculated by dividing the minimum velocity over the maximumvelocity of the downward hepatic vein wave. (a) A patient with cirrhosis shows 0.26 of DI with 7 mmHg of hepatic venous pressure gradient. (b)Another patient with cirrhosis shows 0.72 of DI with 15 mmHg of hepatic venous pressure gradient.

Fig. 8. Change in the hepatic vein waveform and damping index (DI) at baseline (a) and 3 months (b) after propranolol treatment in a patientwith cirrhosis. Quantitative measurement of DI decreased from 0.61 to 0.33 in association with a decrease in the hepatic venous pressuregradient from 18 to 11 mmHg.



Oesophageal variceal pressure assessed by CD EUS-guided manometry significantly correlated with portalpressure by HVPG in vitro study. Therefore, CD EUS-guided manometry of oesophageal varices for theassessment of portal haemodynamics appears promising;however, further validation studies are required (48).Hence, CD EUS and imaging-based variceal pressuremeasurement can be useful as a supplementary tool forthe assessment of portal haemodynamics and risk ofvariceal bleeding.

Future opportunity and challenges: Doppler ultrasoundusing microbubble contrast agents

Opportunity: intrahepatic circulatory time and hepaticvein transit time using microbubble contrast agents

Several reports have suggested that analysis of intrahepa-tic circulatory time (IHCT) is useful for the diagnosis ofcirrhosis and can assess the severity of chronic liverdisease (49–51). IHCT can be calculated from the differ-ence between the arrival time of the microbubbles in thehepatic vein and that in the portal vein or hepatic artery.IHCT and severity of liver disease have an inverserelation, where a decrease in IHCT is accompanied byan increase in the severity of liver disease, which resultsfrom the presence of arteriovenous and portovenousshunts in cirrhotic liver. Similarly, measurement ofhepatic vein transit time (HVTT) using a quantificationsoftware package is also useful in diagnosing cirrhosis,which is calculated as the time from injection to asustained increase in Doppler signal to more than 10%above baseline. An HVTT value of o 21 s has a sensitiv-ity of 100% and a specificity of 80% for the diagnosis ofcirrhosis in 78 patients with chronic liver disease

(51–53). In this regard, we assume that the HVTT valueby Doppler US using microbubble contrast agent mayrepresent the degree of portal pressure, i.e. with increas-ing HVPG, HVTT decreases (Fig. 9).

In a preliminary study with 41 cirrhotic patients, wefound a significant negative correlation between HVTTmeasured by a Doppler microbubble contrast agent andHVPG (Po 0.001, r2 = 0.543) (Fig. 10). The AUROC forthe prediction of severe portal hypertension(HVPGZ12 mmHg) was 0.948, and the sensitivity, spe-cificity, positive predictive value and negative predictivevalue according to an HVTT cutoff value of 17.0 s were78.6, 83.3, 91.7 and 62.5% respectively. HVTT alsoshowed significant correlation with the grade of oeso-phageal varices (F0–F1: 18.0� 3.3 s vs. F2–F3:15.8� 2.5 s, Po 0.05), Child–Pugh’s score and MELDscore (Po 0.05) (unpublished data). A large study deal-ing with the relationship between the measurement ofHVTT by contrast Doppler US and HVPG is expected tostrongly determine the value of HVTT in assessment ofseverity of portal hypertension. Therefore, microbubblecontrast agents may be potentially a supplementaryadjunct to Doppler US for the diagnosis of portalhypertension and cirrhosis.

Challenges: measurement of intravascular pressure usingmicrobubble contrast agents

A new experimental method for noninvasive intravascu-lar pressure measurement, based on the disappearancetime of free gas bubble, was proposed. By transmitting alow frequency, high acoustic amplitude US burst, encap-sulated bubbles ruptured and free gas bubbles werereleased into the desired region, i.e. portal vein where

Table 1. Alterations of haemodynamic parameter in cirrhosis found on Doppler ultrasound

Cirrhosis with PH(compared with normal)

Accuracy andreproducibility Clinical usefulness

Haemodynamic parametersPVV Decreased CV: 3–8% PVV o 15 cm/s is associated with a sensitivity and a

specificity of 88 and 96% for PHPVF IncreasedSVV Increased CV: 8% SPI threshold of 3.0 predict presence of EV in 92% of

patientsSVF IncreasedHA resistance (RI, PI) Increased or no change – ControversialSA resistance (RI, PI) Increased or no change – ControversialRA resistance (RI, PI) Increased – Renal PI4 1.14 is associated with poor prognosis.

Higher than normal renal RI and PI have a high PPV(84–100%) for detection of severe PH.

SMA resistance (RI, PI) Decreased – With liver dysfunction and cirrhosis progress, SMAresistance decrease while SMA flow increase.SMA flow Increased –

HV waveform Flattened CV: 7–10% Monophasic wave form is associated with severe PH, witha sensitivity of 74% and a specificity of 95%.

DI of HV Increased CV: 7% DI4 0.6 predict severe PH (HVPG412 mmHg) with aPPV of 91%

CV, coefficient of variation (calculated by dividing the standard deviation by the mean and multiplying by 100); DI, damping index; HA, hepatic artery;

HV, hepatic vein; PH, portal hypertension; PVV, portal venous velocity; PVF, portal venous flow; RA, renal artery; SA, splenic artey; SMA, superior

mesenteric artery; SPI, splenoportal index; SVF, splenic venous flow; SVV, splenic venous velocity; –, never been reported.



the local pressure can be measured. Higher value of localintravascular pressure results in a quicker disappearancetime of free gas bubbles (54, 55). Microbubble contrastagents are capable of enhancing Doppler US signals.Therefore, changes in ambient pressure affects the re-flectivity of contrast microbubbles, leading to a significantcorrelation between subharmonic signals and hydrostaticpressure (56, 57). This is another candidate of newtechniques for noninvasive intravascular pressure mea-surement using microbubble contrast agents. Althoughthese methods are still in investigative stages, they arenonetheless potential alternatives to Doppler in measuringthe severity of liver diseases, especially portal hypertension.

Conclusions

Conventional Doppler US indices including the portaland splenic venous blood velocity and flow, and arterialRI and PI at hepatic, splenic, superior mesenteric andrenal arteries do not seem to be sensitive enough for theaccurate diagnosis of portal hypertension because of theconflicting results it yields.

There are two important reasons why clinical useful-ness of the above conventional Doppler US indices is stillquestioned.

Firstly, most cirrhotic patients have portosystemicshunts arising from portal hypertension, and the shunt

Fig. 9. Microbubble arriving in the hepatic vein. Ultrasonographical image shows the hepatic vein (white arrows) before the contrast injection(a), and arrival of microbubbles in the hepatic vein (black arrows) after contrast enhancement (b).

Fig. 10. Illustration of measurement of hepatic vein transit time. After an intravenous bolus injection of 2.4 ml of microbubble contrast agent(SonoVues), a recorded time Doppler intensity profile shows early HVTT (13 s) in a patient with 21 mmHg of hepatic venous pressure gradient(a), whereas it shows 28 s of HVTT in a patient with 7 mmHg of hepatic venous pressure gradient (b).



patterns are not unique but vary in complexity in eachpatient. Therefore, the value of Doppler index may differeven between patients with similar portal pressuresbecause of significant variability in portosystemic collat-eral patterns.

In contrast, the presence of intrahepatic shunts result-ing from portal hypertension can be helpful to diagnoseportal hypertension through novel characteristic, such asDoppler US index. It has been recently suggested that theextent of abnormality in Doppler HV waveform isassociated with the degree of HVPG, and a change inthe HV waveform is closely correlated with that ofHVPG. Abnormal flattened HV waveform is thoughtto be because of haemodynamically blunting the effectof variations in central venous pressure during thecardiac cycle, which arises from increased HV inflow viaintrahepatic shunts secondary to portal hypertension.Moreover, under the microbubble contrast enhance-ment, Doppler US detection of decreased hepatic veintransit time (similar to IHCT) because of the presence ofintrahepatic shunts can be useful to assess the severity ofportal hypertension.

Secondly, Doppler US has relatively poor reproduci-bility and accuracy during measurements of Doppler USindices. To reproduce and improve accuracy, cooperativetraining programmes for operators with strict examina-tion protocols would prove to be helpful in reducing therate of intra-and inter-observer variation.

Colour Doppler endoscopic ultrasound focusing onhaemodynamics and visualization of the azygos vein andthe left gastric vein have the potential to be adjunctivemethods for assessment of portal haemodynamics andrisk of variceal bleeding.

Consequently, developments of novel Doppler USindices and techniques are ongoing in order to overcomethe limitations of conventional Doppler US methods inthe diagnosis of portal hypertension and some of themhave the potential to be clinically useful.

In conclusion, haemodynamic evaluation by DopplerUS would be of value as a supplementary tool for theassessment of portal hypertension and response to treat-ment, specifically when HVPG is not feasible or adequateto potentially allow widespread clinical use.

Acknowledgement

This work was supported by a grant from the Ministryfor Health, Welfare and Family Affairs, Republic of Korea(no.A050021).

References

1. Kim MY, Choi H, Baik SK, et al. Portal hypertensivegastropathy: correlation with portal hypertension and prog-nosis in cirrhosis. Dig Dis Sci 2010; 21: 1221–6.

2. Kim MY, Baik SK, Yea CJ, et al. Hepatic venous pressuregradient can predict the development of hepatocellular

carcinoma and hyponatremia in decompensated alcoholiccirrhosis. Eur J Gastroenterol Hepatol 2009; 21: 1241–6.

3. Kim MY, Baik SK. Hyperdynamic circulation in patientswith liver cirrhosis and portal hypertension. Korean JGastroenterol 2009; 54: 143–8.

4. Kim MY, Baik SK, Suk KT, et al. Measurement of hepaticvenous pressure gradient in liver cirrhosis: relationshipwith the status of cirrhosis, varices, and ascites in Korea.Korean J Hepatol 2008; 14: 150–8.

5. Baik SK, Jee MG, Jeong PH, et al. Relationship of hemody-namic indices and prognosis in patients with liver cirrhosis.Korean J Intern Med 2004; 19: 165–70.

6. Lebrec D. Methods to evaluate portal hypertension. Gastro-enterol Clin North Am 1992; 21: 41–59.

7. Baik SK, Kim JW, Kim HS, et al. Recent variceal bleeding:Doppler US hepatic vein waveform in assessment ofseverity of portal hypertension and vasoactive drug re-sponse. Radiology 2006; 240: 574–80.

8. Choi YJ, Baik SK, Park DH, et al. Comparison of Dopplerultrasonography and the hepatic venous pressure gradientin assessing portal hypertension in liver cirrhosis. J Gastro-enterol Hepatol 2003; 18: 424–9.

9. Merkel C, Sacerdoti D, Bolognesi M, et al. Dopplersonography and hepatic vein catheterization in portalhypertension: assessment of agreement in evaluating sever-ity and response to treatment. J Hepatol 1998; 28: 622–30.

10. Schepke M, Raab P, Hoppe A, et al. Comparison of portalvein velocity and the hepatic venous pressure gradient inassessing the acute portal hemodynamic response to pro-pranolol in patients with cirrhosis. Am J Gastroenterol 2000;95: 2905–9.

11. Sato S, Ohnishi K, Sugita S, et al. Splenic artery andsuperior mesenteric artery blood flow: nonsurgical Dop-pler US measurement in healthy subjects and patients withchronic liver disease. Radiology 1987; 164: 347–52.

12. Schneider AW, Kalk JF, Klein CP. Hepatic arterial pulsatilityindex in cirrhosis: correlation with portal pressure.J Hepatol 1999; 30: 876–81.

13. Taourel P, Blanc P, Dauzat M, et al. Doppler study ofmesenteric, hepatic, and portal circulation in alcoholiccirrhosis: relationship between quantitative Doppler mea-surements and the severity of portal hypertension andhepatic failure. Hepatology 1998; 28: 932–6.

14. Vizzutti F, Arena U, Rega L, et al. Performance of Dopplerultrasound in the prediction of severe portal hypertensionin hepatitis C virus-related chronic liver disease. Liver Int2007; 27: 1379–88.

15. Singal AK, Ahmad M, Soloway RD. Duplex Dopplerultrasound examination of the portal venous system: anemerging novel technique for the estimation of portal veinpressure. Dig Dis Sci 2010; 55: 1230–40.

16. Kim MY, Baik SK, Park DH, et al. Damping index ofDoppler hepatic vein waveform to assess the severity ofportal hypertension and response to propranolol in livercirrhosis: a prospective nonrandomized study. Liver Int2007; 27: 1103–10.

17. Siciliani L, Sorbo AR, Pompili M, et al. Hepatic vein transittime(HVTT) of II generation ultrasound contrast agent



(USCA): new tool in assessment of portal hypertension?Preliminary results. Hepatology 2009; 50: 485A–6.

18. Halpern EJ. Science to practice: noninvasive assessment ofportal hypertension – can US aid in the prediction of portalpressure and monitoring of therapy? Radiology 2006; 240:309–10.

19. Baik SK, Choi YJ, Kwon SO, et al. Splanchnic and extra-splanchnic vascular hemodynamics in liver cirrhosis. Kor-ean J Gastroenterol 2000; 35: 466–74.

20. Baik SK, Park DH, Kim MY, et al. Captopril reduces portalpressure effectively in portal hypertensive patients with lowportal venous velocity. J Gastroenterol 2003; 38: 1150–4.

21. Baik SK, Jeong PH, Ji SW, et al. Acute hemodynamic effectsof octreotide and terlipressin in patients with cirrhosis: arandomized comparison. Am J Gastroenterol 2005; 100:631–5.

22. Suk KT, Kim MY, Park DH, et al. Effect of propranolol onportal pressure and systemic hemodynamics in patientswith liver cirrhosis and portal hypertension: a prospectivestudy. Gut Liver 2007; 1: 159–64.

23. Zironi G, Gaiani S, Fenyves D, et al. Value of measurementof mean portal flow velocity by Doppler flowmetry in thediagnosis of portal hypertension. J Hepatol 1992; 16:298–303.

24. Kayacetin E, Efe D, Dogan C. Portal and splenic hemody-namics in cirrhotic patients: relationship between esopha-geal variceal bleeding and the severity of hepatic failure.J Gastroenterol 2004; 39: 661–7.

25. Bolondi L, Gaiani S, Barbara L. Accuracy and reproduci-bility of portal flow measurement by Doppler US. J Hepatol1991; 13: 269–73.

26. Ohnishi K, Saito M, Koen H, et al. Pulsed Doppler flow as acriterion of portal venous velocity: comparison with ci-neangiographic measurements. Radiology 1985; 154: 495–8.

27. Zoli M, Marchesini G, Brunori A, et al. Portal venous flowin response to acute beta-blocker and vasodilatatory treat-ment in patients with liver cirrhosis. Hepatology 1986; 6:1248–51.

28. Gaiani S, Bolondi L, Li Bassi S, et al. Effect of meal onportal hemodynamics in healthy humans and in patientswith chronic liver disease. Hepatology 1989; 9: 815–9.

29. Sabba C, Merkel C, Zoli M, et al. Interobserver andinterequipment variability of echo-Doppler examinationof the portal vein: effect of a cooperative training program.Hepatology 1995; 21: 428–33.

30. Nelson RC, Sherbourne GM, Spencer HB, et al. Splenicvenous flow exceeding portal venous flow at Dopplersonography: relationship to portosystemic varices. Am JRoentgenol 1993; 161: 563–7.

31. Chong WK, Malisch TW, Mazer MJ. Sonography of trans-jugular intrahepatic portosystemic shunts. Semin Ultra-sound CT MR 1995; 16: 69–80.

32. Surratt RS, Middleton WD, Darcy MD, et al. Morphologicand hemodynamic findings at sonography before and aftercreation of a transjugular intrahepatic portosystemic shunt.Am J Roentgenol 1993; 160: 627–30.

33. Foshager MC, Ferral H, Nazarian GK, et al. Duplexsonography after transjugular intrahepatic portosystemic

shunts (TIPS): normal hemodynamic findings and efficacyin predicting shunt patency and stenosis. Am J Roentgenol1995; 165: 1–7.

34. Chong WK, Malisch TA, Mazer MJ, et al. Transjugularintrahepatic portosystemic shunt: US assessment withmaximum flow velocity. Radiology 1993; 189: 789–93.

35. Feldstein VA, Patel MD, LaBerge JM. Transjugular intrahe-patic portosystemic shunts: accuracy of Doppler US indetermination of patency and detection of stenoses. Radi-ology 1996; 201: 141–7.

36. Middleton WD, Teefey SA, Darcy MD. Doppler evaluationof transjugular intrahepatic portosystemic shunts. Ultra-sound Q 2003; 19: 56–70.

37. Zhang L, Duan YY, Li JM, et al. Hemodynamic features ofDoppler ultrasonography in patients with portal hyperten-sion: intraoperative direct measurement of portal pressurein the portal venous system. J Ultrasound Med 2007; 26:1689–96.

38. Baik SK, Kim KH, Jeong YS, et al. Pulsatility index of renalartery in patients with liver cirrhosis. J Korean Soc MedUltrasound 2000; 19: 71–6.

39. Seo JI, Baik SK, Kim JW, et al. Renal function indicespredicting the prognosis of patients with liver cirrhosis.Korean J Hepatol 2001; 7: 140–6.

40. Berzigotti A, Casadei A, Magalotti D, et al. Renovascularimpedance correlates with portal pressure in patients withliver cirrhosis. Radiology 2006; 240: 581–6.

41. Sacerdoti D, Gaiani S, Buonamico P, et al. Interobserverand interequipment variability of hepatic, splenic, andrenal arterial Doppler resistance indices in normal subjectsand patients with cirrhosis. J Hepatol 1997; 27: 986–92.

42. Bolondi L, Li Bassi S, Gaiani S, et al. Liver cirrhosis: changesof Doppler waveform of hepatic veins. Radiology 1991; 178:513–6.

43. Ohta M, Hashizume M, Tomikawa M, et al. Analysis ofhepatic vein waveform by Doppler ultrasonography in 100patients with portal hypertension. Am J Gastroenterol 1994;89: 170–5.

44. Colli A, Cocciolo M, Riva C, et al. Abnormalities ofDoppler waveform of the hepatic veins in patients withchronic liver disease: correlation with histologic findings.Am J Roentgenol 1994; 162: 833–7.

45. Ohta M, Hashizume M, Kawanaka H, et al. Prognosticsignificance of hepatic vein waveform by Doppler ultra-sonography in cirrhotic patients with portal hypertension.Am J Gastroenterol 1995; 90: 1853–7.

46. Hino S, Kakutani H, Ikeda K, et al. Hemodynamic assess-ment of the left gastric vein in patients with esophagealvarices with color Doppler EUS: factors affecting develop-ment of esophageal varices. Gastrointest Endosc 2002; 55:512–7.

47. Lee YT, Sung JJ, Yung MY, et al. Use of color Doppler EUSin assessing azygos blood flow for patients with portalhypertension. Gastrointest Endosc 1999; 50: 47–52.

48. Pontes JM, Leitao MC, Portela F, et al. EndosonographicDoppler-guided manometry of esophageal varices: experi-mental validation and clinical feasibility. Endoscopy 2002;34: 966–72.



49. Searle J, Mendelson R, Zelesco M, et al. Non-invasiveprediction of the degree of liver fibrosis in patients withhepatitis C using an ultrasound contrast agent. A pilotstudy. J Med Imaging Radiat Oncol 2008; 52: 130–3.

50. Staub F, Tournoux-Facon C, Roumy J, et al. Liver fibrosisstaging with contrast-enhanced ultrasonography: prospec-tive multicenter study compared with METAVIR scoring.Eur Radiol 2009; 19: 1991–7.

51. Goyal N, Jain N, Rachapalli V, et al. Non-invasive evalua-tion of liver cirrhosis using ultrasound. Clin Radiol 2009;64: 1056–66.

52. Blomley MJ, Lim AK, Harvey CJ, et al. Liver microbubbletransit time compared with histology and Child-Pugh scorein diffuse liver disease: a cross sectional study. Gut 2003; 52:1188–93.

53. Lim AK, Taylor-Robinson SD, Patel N, et al. Hepatic veintransit times using a microbubble agent can predict disease

severity non-invasively in patients with hepatitis C. Gut2005; 54: 128–33.

54. Bouakaz A, Frinking PJ, de Jong N, et al. Noninvasivemeasurement of the hydrostatic pressure in a fluid-filledcavity based on the disappearance time of micrometer-sized free gas bubbles. Ultrasound Med Biol 1999; 25:1407–15.

55. Frinking PJA, De Jong N, Cespedes EI. Scattering proper-ties of encapsulated gas bubbles at high ultrasound pres-sures. J Acoust Soc Am 1999; 105: 1989–96.

56. Forsberg F, Liu JB, Shi WT, et al. In vivo pressure estimationusing subharmonic contrast microbubble signals: proof ofconcept. IEEE Trans Ultrason Ferroelectr Freq Control 2005;52: 581–3.

57. Shi WT, Forsberg F, Raichlen JS, et al. Pressure dependenceof subharmonic signals from contrast microbubbles. Ultra-sound Med Biol 1999; 25: 275–83.



Hemodynamic Evaluation of Portal Hypertension

Documents

Transcript of Hemodynamic Evaluation of Portal Hypertension