ultrasound examination portal hypertension by EFSUMB

Document for the EFSUMB Education and Professional Standard Committee.

Clinical recommendations for the performance and reporting of ultrasound examination for portal hypertension Annalisa Berzigotti1,2 , Fabio Piscaglia3 and the EFSUMB Education and Professional Standard Committee

Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomediques

August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd); 2Abdominal Imaging Section, Centre Diagnostic per la Imatge (CDIC), Hospital Clinic i Provincial, c/Villarroel 170, 08036, Barcelona, Spain. 3

Division of Internal Medicine, Department of Digestive Disease and Internal Medicine,

General and University Hospital S.Orsola-Malpighi, Bologna, Italy

Address for correspondence: Annalisa Berzigotti, M.D., Ph.D., Abdominal Imaging Section, Centre Diagnostic per la Imatge (CDIC), Hospital Clinic i Provincial c/Villarroel 170 08036, Barcelona, Spain e-mail: aberzigo@clinic.ub.es

2 Preface This document contains clinical recommendations about how to perform and report ultrasound examinations in patients with suspected or previously diagnosed portal hypertension. To ensure an updated content, a bibliographic research on studies involving ultrasound in this specific field was conducted (Medline, last updated in March 2011). The document, which is intended as straightforward and concise, has been structured as follows: -

Introduction containing the essential clinical background of portal hypertension

Main clinical information derived from US in this field (further commented in Table 1, Table 2 and Table 4)

Technical details of US-Doppler examination in this field (further commented in Table 3)

EFSUMB endorsed recommendations on how reports of US examinations have to be arranged. In particular a list of parameters related to presence of clinically significant portal hypertension (CSPH) which should be included in all US report according to the level of care of the ultrasound unit in which the patients is investigated (primary, secondary or tertiary referral center; Table 4 and 5)

All the contents are expanded and discussed in a free access CME-article to be published in Ultraschall in der Medizin-European Journal of Ultrasound, which also contains US images to illustrate the most important aspects of duplex-US assessment in portal hypertension.

3 Introduction Portal hypertension (PH) is a frequent clinical syndrome hemodynamically defined by an increase in the portal pressure gradient (difference between portal vein pressure and inferior vena cava pressure) over the normal limit of 5 mmHg (1). The clinical features of this syndrome include gastroesophageal varices formation and rupture, ascites and hepato-renal syndrome, which are the main causes of death and liver transplantation in patients with cirrhosis. In Western countries 90% of cases of PH are due to liver cirrhosis, which is its main intrahepatic cause, while rarer etiologies include pre-hepatic causes such as portal vein thrombosis (more common in children), and post-hepatic causes, such as hepatic veins thrombosis (Table 1). In parenchymal chronic liver diseases PH begins to develop as a consequence of the architectural disarrangement induced by scarring and nodules, which induce an increased resistance to blood inflow. In later phases, when PH is already established, it is maintained by splanchnic vasodilatation and formation of porto-systemic collaterals which induce an increase in porto-collateral blood flow (for similarity and generalization of Ohmâ&#x20AC;&#x2122;s law: Voltage = Resistance by Current, in hemodynamics it can be considered Pressure=Resistance * Flow) (1). The gold standard for PH assessment in cirrhosis is the invasive measurement of hepatic venous pressure gradient (difference between wedged hepatic venous pressure and free hepatic venous pressure, HVPG) by means of hepatic vein catheterization. HVPG over 10-12 mmHg defines clinically significant portal hypertension (CSPH), since all complications can occur when pressure increases above this threshold (1). The development of clinically significant portal hypertension (CSPH, HVPG â&#x2030;Ľ 10 mmHg) is a key prognostic step in the natural history of cirrhosis; even in patients with compensated cirrhosis and no gastroesophageal varices, the presence of CSPH is an independent predictor of clinical decompensation (namely: ascites, variceal bleeding, hepatic encephalopathy, jaundice, hepato-renal syndrome, spontaneous bacterial peritonitis) and death (2). Therefore, in patients with chronic liver diseases CSPH should be diagnosed promptly to allow accurate risk stratification and to provide appropriate clinical management, including endoscopy screening for esophageal varices and pharmacological treatment when indicated. Even if HVPG gives irreplaceable information, it is invasive, relatively expensive in terms of

4 disposable and need for angiography room occupancy and its use is currently restricted to tertiary care hospitals.

Ultrasound (US) is the first line imaging technique used in patients with suspected PH, since it is non-invasive, repeatable and cheap. Therefore, all US examiners should be able to detect and report correctly the most important signs of PH. Most US signs of PH are independent of its underlying cause, and their interpretation should always be integrated with clinical information. On the other hand, when patients show overt clinical features of PH and no other data is available, US examination facilitates the classification of PH. These recommendations are intended as a guide for standardizing and ensuring a high-quality examination and reporting of US in patients with suspected/established portal hypertension.

Clinical scenario, indications and main information derived from US in this field There are four main clinical scenarios of application of US in the field of portal hypertension: 1. Patients with clinical/laboratory findings of PH in the absence of known chronic liver disease (CLD) The chance of encountering non-cirrhotic causes of PH is increased in these patients, and special attention should be paid in the assessment of vascular patency, since portal vein thrombosis and hepatic veins thrombosis are the most frequent causes of non-cirrhotic portal hypertension. Colour (and Power)-Doppler US (CDUS) is > 90% accurate for diagnosing portal vein thrombosis/portal cavernoma and hepatic veins thrombosis (Budd-Chiari syndrome); cardiac causes, and arterioportal fistulae can be also identified. Rarer causes of PH (including idiopathic portal hypertension or nodular regenerative hyperplasia) should be suspected in patients with signs of PH and no other apparent cause, and should be investigated with appropriate invasive means.

5 RECOMMENDATION In patients with clear clinical signs of portal hypertension duplex-Doppler US is an accurate method to establish the causes of portal hypertension.

Specifically, portal vein thrombosis and hepatic vein thrombosis can be identified or ruled-out by duplex-Doppler US

2. US assessment of PH in patients with known compensated chronic liver disease (CLD) Up to 70% of patients with compensated cirrhosis have CSPH (defined as HVPGď&#x201A;ł10 mmHg). Therefore, signs of cirrhosis should be always investigated; the most accurate single sign of cirrhosis is liver surface nodularity examined by a linear transducer (1, 3, 4). Table 2 shows the most important US signs of PH. US signs are highly specific for the non-invasive diagnosis of CSPH, but their sensitivity is moderate. The fundamental signs are: -

Porto-systemic abdominal collaterals

Splenomegaly

Portal vein, splenic vein and mesenteric vein dilatation

Reduction of the respiratory variations of splenic and mesenteric vein diameter

Hepatofugal flow in the portal vein system

Reduction of portal vein blood velocity

Subclinical ascites

Ancillary US parameters of PH are the congestion index of the portal vein (5); flattening of physiologic phasicity of hepatic veins Doppler flow pattern (6, 7) and arterial parameters (renal Doppler impedance indexes, splenic artery Doppler impedance indexes and superior mesenteric artery Doppler impedance indexes) (8, 9). Even if the signs listed above, especially when combined, can reliably diagnose CSPH, none of them allows an exact numerical estimation of the HVPG. Portal vein thrombosis and/or to hepatocellular carcinoma can cause abrupt increases in portal pressure leading to episodes of clinical decompensation.

6 Therefore, anytime new clinical events occur, patients should be re-assessed by USDoppler to rule-out these complications.

RECOMMENDATION All patients with chronic liver diseases should undergo a US-Doppler examination at the time of first diagnosis to assess the presence of signs of cirrhosis and portal hypertension, since US signs hold a satisfactory sensitivity and a high specificity for the diagnosis of these conditions.

The essential parameters to be described are: signs of cirrhosis; portal vein patency, diameter and direction of flow; splenic vein and mesenteric vein diameter and its respiratory variation, and direction of flow, spleen size, presence/absence of porto-systemic abdominal collaterals and presence/absence of ascites.

Most US-Doppler signs show high specificity for the diagnosis of CSPH. Since US-Doppler is non-invasive and repeatable, the search of these specific findings according to the level of care reported in Table 3 is recommended.

In patients with cirrhosis US-Doppler examination should be repeated every time a new clinical event occurs, to rule out portal vein thrombosis and hepatocellular carcinoma, which are frequent causes of worsening of portal hypertension and clinical decompensation.

3. Prognostic information provided by US findings in patients with cirrhosis and PH Porto-systemic collaterals are associated with an increased prevalence of esopheageal varices, with a higher risk of first clinical decompensation of cirrhosis (10), and with the onset of hepatocellular carcinoma (11). The development/increase in number of porto-systemic collaterals, and spleen enlargement on follow-up have been associated with a greater proportion of variceal formation and growth (12, 13). Increased congestion index of the portal vein

7 independently predicted first variceal bleeding in the following 6 months (but not on the long-term) in one study (14). A slow portal vein flow (averaged maximum velocity <15 cm/s) was the only variable independently associated with a higher risk of developing non-malignant (bland) portal vein thrombosis in a recent prospective study in cirrhotic patients (15). Increased intrarenal arteriolar Doppler RI (RI â&#x2030;Ľ0.70) indicates downstream arterial vasoconstriction and is a useful sign contributing to diagnosing hepato-renal syndrome (16, 17). A small liver size, spleen size over 14.5 cm, mean portal vein velocity < 10 cm/s and loss of pulsatility of hepatic veins have all been associated to higher mortality on follow-up in patients with compensated cirrhosis. A more detailed discussion of these parameters can be found in the CME-article.

4. Follow-up of patients receiving treatment for portal hypertension Treatment aiming at decreasing portal pressure are a) pharmacological treatment, mainly consisting in betablockers or betablockers plus nitrates, b) surgical portosystemic shunts and c) transjugular intrahepatic portosystemic shuns (TIPS). Doppler ultrasound has an established clinical role in the assessment of the two latter situations (see Table 3), whereas its usefulness in the former is uncertain. RECOMMENDATION Doppler-US does not provide accurate information on the hemodynamic response to beta-blockers in patients with cirrhosis and portal hypertension.

Doppler-US is useful and recommended to non-invasively follow-up patients with TIPS or porto-systemic surgical shunts.

Technical details: how to conduct US and Doppler US examinations of the liver, spleen and portal venous system (Table 3). US and Doppler-US examination should be performed after at least 6 hour fast, by using real-time scanners provided with pulsed and colour/power Doppler modules (convex transducers; mean frequencies used are between 3.5 and 5 MHz; linear high-frequency transducers 7.5-10 MHz are useful to assess liver surface).

8 For Doppler parameters at least three consistent consecutive measurements should be taken, and their average used as the final result. Note that the normal values described in the table have been set according to the data of published studies, which are mostly case series or case-control studies; randomized controlled trials in this field are lacking, and better evidence cannot be provided.

List of parameters related to presence of CSPH which should be included in all US report grouped according to the level of care of the ultrasound unit in which the patients is investigated (primary, secondary or tertiary referral center) Table 4 and Table 5 summarize the information which should be given in US reports according to the level of care of the referral center. A list of parameters which should be intended for research use and not for clinical practice is also provided.

9 Table 1. Causes of portal hypertension according to the site of increased resistance to portal blood flow, and usefulness of US and Doppler-US for diagnosis. Site of increased resistance to portal blood flow

Prehepatic

Main causes • Thrombosis of the portal system • Congenital stenosis of the portal vein • Arteriovenous fistulae (splenic, aortomesenteric, aortoportal, and hepatic artery-portal vein) • Partial nodular transformation • Nodular regenerative hyperplasia • Congenital hepatic fibrosis • Peliosis hepatis

Presinusoidal

Intrahepatic

Ultrasound usefulness for specific diagnosis Yes: Lack of patency or abnormal morphology of portal vein system; visualization of fistulae or of their hemodynamic consequences Only in some cases (underlined in the causes column):

• Polycystic liver disease

Multiple hepatic cysts

• Schistosomiasis

Wall thickening and increased echogenicity of the portal veins and its branches; anechoic portal vein surrounded by echogenic fibrous tissue configuring the typical “bull’s eye” (18)

• Idiopathic portal hypertension • Hypervitaminosis A • Arsenic, copper sulfate, and vinyl chloride monomer poisoning • Sarcoidosis • Tuberculosis • • Amyloidosis • Acute fatty liver of pregnancy • Liver cirrhosis (alcoholic, viral, etc...)

In the remaining: nonspecific liver alterations Yes In cirrhosis: liver surface irregularity and changes of liver morphology

Sinusoidal • Sinusoidal obstruction syndrome (SOS)* also known as venoocclusive disease

Intrahepatic

• Budd-Chiari syndrome

Posthepatic

• Congenital malformations and thrombosis of the IVC • Constrictive pericarditis • Tricuspid valve diseases

In SOS: hepatomegaly, ascites, gallbladder wall thickening and decreased or reversed portal venous flow(19) Yes Lack of patency of hepatic veins

Postsinusoidal Yes Lack of patency of IVC Dilatation and abnormal flow pattern of hepatic veins

10 Table 2. Main reported US and Doppler-US signs of portal hypertension in patients with chronic liver diseases. Accuracy in populations including patients with other relevant comorbidity (cardiac disease, haematologic diseases) is unknown. *Gold standard for PH diagnosis: HVPG measurement or direct measurement; sensitivity efers to patients with HVPG  12 mmHg.

Refs Dilatation of portal vein (13 mm) Portal venous system

(20, 21)

(22, 23) Dilatation of splenic vein (SV) and superior mesenteric vein (SMV) (11 mm)

Sensitivity <50%

Specificity 90-100%

72%

100%

80-88%

80-96%

Not reported; sign prevalence: 8.3% of unselected pts 67-95%

100%

Reduction of portal vein blood flow velocity (Time Averaged Max Vel < 16 cm/s; mean vel < 10 cm/ s) Reversal of portal vein blood flow

(24, 25)

Increased portal vein congestion index (0.08)

(5, 25)*

Reduction of respiratory variation of diameter in SV or SMV (<40%)

(20)

79.7%

100%

Spleen

Splenomegaly (diameter > 12 cm and/or area 45 cm2)

(27)*

93%

36%

Splenic artery

Increased Doppler impedance indexes in the intraparenchymal branches (RI ≥0.63, PI≥1.00)

(28)*(29, 30)

84.6%

70.4%

Hepatic artery

Increased Doppler resistive index in the intrahepatic branches (>0.78)

(30, 31)

50%

100%

Renal artery

Increased Doppler resistive index of the right interlobar renal artery ( 0.65)

(28)*

79.5%

59.3%

(28)*

85.7%

65.2%

(32)*

83%

100%

SMA

Decreased Doppler pulsatility index ( 2.70) Presence of porto-systemic collateral circulation

(26)

100%

Table 3. Technical details of US examination for portal hypertension.

Where to measure

Diameter

Portal vein (PV)

Velocity

How to measure and normal values

- Measure PV diameter as distance from inner anterior wall to inner posterior wall, perpendicular to the long portal axis, at the cross with hepatic artery or slightly downstream (but ≥2 cm upstream from portal bifurcation) wherever the vessel walls are best visualized: aim to a large angle between US waves and portal walls. - Diameter is to be preferably measured with grey scale B-mode ultrasound, since CDUS, despite facilitating identification of the vessel, also implies a risk of overestimation of diameter, related to the size of the color pixels. Oblique-transversal - Measured during normal suspended respiration in the supine position (forced inspiration or left side decubitus make measurement unreliable) scan in - Normal < 12 mm (diameter increases according to body surface) epigastrium/right - Place sample volume (≥50% of the diameter of PV) in the middle of the lumen at the cross with hepatic artery (33) subcostal region to - Doppler angle preferably set at 55°, but keep it always 60º visualize PV along its - Doppler flowmetry, recommended PRF=4 kHz; wall filter=100 Hz (decrease to longitudinal axis for at 50 Hz if very slow flow) - concurrent display of colour-Doppler image and Doppler flowmetry least 3-4 cm measurement if feasible (top equipments) or freeze B-mode image while displaying Doppler flowmetry tracings - Manual tracing of Doppler signal for at least 2 cardiac cycles or ≥2-3 seconds; mean maximum velocity is calculated by the equipment in cm/s; mean velocity can be approximated as time averaged max vel*0.57. Direct measurement of mean portal vein velocity is technically feasible but strongly influenced by Doppler setting, resulting in low reproducibility. Measurement of time averaged maximal velocity is recommended - Normal time averaged maximum vel > 20-24cm/s$

Calculated as PV cross sectional area (diameter/2*diameter/2*) / mean portal flow velocity Normal < 0.075

Congestion index Transversal scan in Splenic vein

Diameter

epigastrium, to visualize SV longitudinal axis Longitudinal scan in

Superior mes. vein

Diameter

epigastrium, to visualize SMV longitudinal axis

Measure SV diameter at about 1-2 cm upstream the spleno-portal confluence, during suspended normal respiration in supine position Diameter ≥ 10 mm is to be considered enlarged

Measure SMV diameter at about 1-2 cm upstream the mesenteric-portal confluence, during suspended normal respiration in supine position Diameter ≥ 10 mm is to be considered enlarged

At least the following vessels should be actively looked for by US and color-Doppler US: Portocollateral circulation

Presence or absence

Paraumbilical vein: falciform ligament Left gastric vein: epigastric region posterior to left hepatic lobe. Check also flow direction. Short gastric veins: left hypcondrium posterior to the upper pole of the spleen Spleno-renal circulation: left hypocondrium between the lower half of the spleen and the left kidney

Hepatic

Diameter and

veins

patency

Right subcostal or right intercostal scan (the Normal diameter ≤ 1 cm latter especially for Doppler flow tracing

Phasicity of flow

measurement) allowing Sample volume should be about the same as diameter of the vein; quantitative a main axis information (flow velocity) is restricted to selected cases (stenosis) visualization Sampling at 1-3 cm Normal triphasic flow. Flow tracings to be assessed during suspended normal from IVC respiration (forced inspiration may flatten the tracing, however, if regularly triphasic during forced inspiration a normal tracing is anyway ascertained). Assessment at best in supine position, but in left decubitus also acceptable. Transversal/longitudina

Inferior

Diameter and

vena cava

patency

l scans from the thoraco-abdominal

Normal tri-quadriphasic flow; tend to collaps in expiration. Caliber <2 cm.

region (intercostal and subcostal) Color-Doppler helps in finding the site of measurement, adjacent to the lobar branches of the portal vein. Right branch visualized usually at best through an intercostal scan at its entrance in the liver, left branch through an epigastric scan,

Hepatic artery

Intraparenchymal Main lobar branches in Impedance indexes the right and left lobe

either during suspended normal respiration or during forced inspiration (to be kept no longer than approximately 10 seconds, otherwise hypoxia induces vasodilatation). Increase PRF to improve Doppler tracings, aiming at having a trace occupying approximately Âž of the screen height. At least 2 identical consecutive complete arterial tracings are required (at best â&#x2030;Ľ3) to confirm that no change in pulsed Doppler insonation angle occurred during the recording of

tracings in any cardiac cycle. Normal: RI < 0.65-0.70; PI <1.20 Color-Doppler helps in finding the site of measurement, usually parallel to the intrasplenic veins. Adjust PRF to improve Doppler tracings, aiming at having a trace occupying approximately ¾ of the screen height, after having lowered the zero Doppler line. Angle of insonation preferable between 20° and 60°. Splenic

Intraparenchymal

artery

Impedance indexes

Main branches 1 cm

Measurements through a left intercostal space in the supine position during either

after entering the

suspended normal respiration or forced inspiration (to be kept no longer than

parenchyma

approximately 10 seconds, otherwise hypoxia induces vasodilation). Sample volume usually 2-4 mm, often larger than arterial diameter. At least 2 identical complete arterial tracings are required (at best ≥3) to confirm that no change in pulsed Doppler insonation angle occurred during the tracing of any cardiac cycle. Normal: RI < 0.63; PI <1.00 Site of assessment. 3-5 cm distal to the origin, at best shortly after the initial

Superior mesenteric artery

Diameter and

Longitudinal scan in

curve, where the course is straight. Sample volume set as large as the artery.

epigastrium, to

Adjust PRF to improve Doppler tracings, aiming at having a trace occupying

impedance indexes visualize SMA longitudinal axis

approximately ¾ of the screen height. Normal in fasting state: RI > 0.84; PI >3.20. Diameter ≤6 mm. At least 2 identical consecutive complete arterial tracings are required (at best ≥3) to confirm that no change in pulsed Doppler

insonation angle occurred during the tracing of any cardiac cycle.

Visualize the kidney as superficial as possible (usually through a rather posterior approach). Preliminary CDUS is strongly recommended to visualize the arterial tree. Keep CDUS PRF low (700-800 Hz). Measurements taken either during suspended normal respiration or forced inspiration (to be kept no longer than approximately 10 seconds, otherwise hypoxia induces vasodilation). Sample Renal arteries

Intraparenchymal Interlobar (or

volume usually 2-4 mm, larger than artery diameter. Adjust PRF to improve

Impedance indexes interlobular) arteries

Doppler tracings, aiming at having a trace occupying approximately Âž of the screen height, after having lowered the zero Doppler line. At least 2 identical consecutive complete arterial tracings are required (at best â&#x2030;Ľ3) to confirm that no change in pulsed Doppler insonation angle occurred during the tracing of any cardiac cycle. Normal: RI <0.70 (in adult patients); PI <1.15-1.20

TIPS

Patency

Intercostal scan

- Assess TIPS patency (presence of flow) by colour-Doppler

allowing TIPS

- Assess flow velocity within TIPS (proximal, medium and distal part); a focal

visualization from the portal vein up to the

increase in velocity suggests TIPS dysfunction/stenosis - Evaluate the direction of flow within the intrahepatic branches of portal vein;

hepatic vein

hepatofugal (reversed) flow is associated with normal TIPS function, while the re-appearance of hepatopetal flow (if previously reversed) in the follow-up is associated with TIPS dysfunction - Measure portal vein velocity: a progressive reduction in subsequent controls suggests TIPS dysfunction - Presence of ascites is highly suggestive of TIPS dysfunction

Transverse and longitudinal scan in the anatomical site Surgical shunts

Patency

B-mode and Colour Doppler examination if possible; if not feasible due to

according to the type of abdominal gas evaluate indirect signs of patency: absence of ascites and reversal shunt (spleno-renal

of flow in the portal vein (porto- and meso-cava shunt) or in the splenic vein

shunt; porto-caval

(proximal spleno-renal shunt) suggest patency

shunt; meso-cava shunt) $

Normality range should be assessed for every US equipment, since interequipment variability is large.

Table 4. Information to be included in all US reports of any patient with a request to investigate presence of portal hypertension or any patient in whom chronic liver disease or ascites of unknown origin is diagnosed, subgrouped according to the level of care of the ultrasound unit providing the examination.

US/ US-Doppler Parameter

Presence/absence of signs of cirrhosis (at least the

Primary

Secondary

Tertiary

Intended for research use

referral

and not for clinical

center

practice

pattern of liver surface, preferentially with a linear probe, and liver echotexture) and focal lesions in the liver Patency of hepatic veins (HV) Course (linearity) and diameter of HV (semiquantitative:

decreased, normal or increased) Morphology of HV Doppler flow In case of Budd-Chiari syndrome: assessment of the presence of intrahepatic collateral circulation and enlargement of short hepatic veins in the caudate lobe; use of contrast agents to confirm the diagnosis

Portal vein flow velocity

In case of thrombosis: assess whether it is partial or

Patency and diameter of portal vein

Patency of intrahepatic main and segmental branches of portal vein Direction of flow into the portal vein

total; if partial thrombosis state, approximately, the percent of lumen occupied by thrombosis Use of CDUS + CEUS with contrast agents to confirm

the diagnosis of portal thrombosis in difficult cases and to characterize the thrombus (benign vs. malignant thrombus) Portal blood flow volume

X X

Patency, diameter and flow direction in splenic vein and superior mesenteric vein Assessment of respiratory variation of the diameter of splenic vein and superior mesenteric vein Spleen size (longitudinal diameter and/or cross sectional area) Presence or absence of portosystemic collateral vessels

(if present, location is to be reported) Presence or absence of ascites Semi-quantitative assessment of the amount of ascites

(minimal, mild, moderate, massive) Diameter of main hepatic artery; hepatic artery velocity

Intrahepatic artery Doppler pulsatility and resistance

index (right and left lobe) Hepatic artery blood flow

Total hepatic blood flow

Diameter of splenic artery; splenic artery velocity

Diameter of superior mesenteric artery; SMA velocity

Intraparenchymal splenic artery Doppler pulsatility and

resistance indexes Intraparenchymal renal (interlobar artery) Doppler

pulsatility and resistance indexes Superior mesenteric artery Doppler pulsatility and

resistance indexes Liver vascular index (34)

Portal hypertension index (30)

Porto-hepatic transit time of contrast medium by CEUS

(35) Regional hepatic perfusion by CEUS (36)

Table 5. Summary of parameters to be reported according to the level of the Ultrasound Unit, and clinical correlates. Recommendation endorsed by the EFSUMB Education and Professional Standard Committee. Level of US examination

Parameters to be assessed

Clinical correlates of the US and Doppler US findings

1) Porto-systemic collaterals are pathognomonic features of Clinically Significant Portal Hypertension (CSPH), regardless of the presence of cirrhosis, suggests the presence of gastroesophageal varices and has been associated with a higher risk of first clinical decompensation of cirrhosis; development/increase in number of porto-systemic collaterals has been associated with a greater proportion of variceal formation and growth

Primary level

Signs of cirrhosis (liver profiles, hepatic morphology changes and echotexture); focal liver lesions; patency and diameter of hepatic veins; patency, diameter and flow direction of the portal vein; presence of ascites; presence of portal systemic collaterals; spleen size

2) Portal vein thrombosis is diagnostic of portal hypertension (in the absence of cirrhosis its etiologic assessment requires specific investigations). 3) Reversal of flow within any main vessel of portal system is diagnostic of portal hypertension 4) Splenomegaly, ascites and portal vein dilation are all highly suggestive of CSPH only in patients with cirrhosis; in the absence of cirrhosis and hepatic/portal veins obstruction other causes are to be intensively seeked for. 5) Increased spleen size is predictive of mortality in cirrhosis, and spleen enlargement on follow-up has been associated with a greater proportion

of variceal formation and growth, and with a higher risk of first clinical decompensation of cirrhosis 5) Obstruction of hepatic veins in the absence of liver tumors is pathognomonic of Budd-Chiari syndrome (whose etiologic assessment requires specific investigations). 6) Enlargement of the hepatic veins (and inferior vena cava) suggests a post-hepatic cause of CSPH (cardiac liver). 7) A small liver size is associated with mortality in cirrhosis All the above, plus: 1) Reversal of flow in the right portal vein or in the splenic or superior mesenteric veins are diagnostic of CSPH

Secondary level

All parameters of primary level plus: course, diameter and flow Doppler tracing in hepatic veins; patency and flow direction in the intrahepatic portal branches and in splenic and superior mesenteric veins; portal vein flow velocity; portal vein thrombus extension; assessment of respiratory variations of caliber in the splenic and superior mesenteric veins.

2) Increased congestion index of the portal vein independently predicted 6-moths risk of first variceal bleeding 3) Decrease in portal vein flow velocity contributes to the diagnosis of cirrhosis in compensated chronic liver disease; severe decrease in portal vein flow velocity indicates CSPH, is a negative prognostic factor in compensated cirrhosis, and might predict the risk of non-malignant portal vein thrombosis 4) Ridigity (absence of respiratory variations) of splenic and superior mesenteric veins is highly suggestive for portal hypertension 5) Presence of portal vein thrombosis, even if partial and not involving the portal trunk (splenic vein or superior mesenteric vein, and lobar

intrahepatic branches), is pathognomonic of portal hypertension 6) flattening of hepatic vein flow tracing occurs in chronic liver disease; when occurring in cirrhosis has a negative prognostic value

All the above, plus: 1) increase in splenic artery impedance indexes is highly suggestive of CSPH in patients with cirrhosis Tertiary (referral) level

All parameters of primary and secondary levels plus: splenic and renal arteries; characterization and study of extension of portal vein thrombosis; thorough assessment of hepatic veins.

2) increase in renal artery impedances indexes is an independent predictor of hepato-renal syndrome 3) distinction between bland and malignant portal vein thrombosis 4) complete overview of the vascular situation in patients with BuddChiari syndrome, including thorough assessment of hemodynamics. 5) Diagnosis of non-cirrhotic causes of portal hypertension (fistulae, cardiac causes, etc.)

References 1. Bosch J, Garcia-Pagan JC, Berzigotti A, Abraldes JG. Measurement of portal pressure and its role in the management of chronic liver disease. Semin Liver Dis 2006 Nov;26(4):348-362. 2. D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 2006 Jan;44(1):217-231. 3. Colli A, Fraquelli M, Andreoletti M, Marino B, Zuccoli E, Conte D. Severe liver fibrosis or cirrhosis: accuracy of US for detection-analysis of 300 cases. Radiology 2003 Apr;227(1):89-94. 4. Bonekamp S, Kamel I, Solga S, Clark J. Can imaging modalities diagnose and stage hepatic fibrosis and cirrhosis accurately? J Hepatol 2009 Jan;50(1):17-35. 5. Moriyasu F, Nishida O, Ban N, Nakamura T, Sakai M, Miyake T, et al. "Congestion index" of the portal vein. AJR Am J Roentgenol 1986 Apr;146(4):735-739. 6. Bolondi L, Li Bassi S, Gaiani S, Zironi G, Benzi G, Santi V, et al. Liver cirrhosis: changes of Doppler waveform of hepatic veins. Radiology 1991 Feb;178(2):513-516. 7. Kim MY, Baik SK, Park DH, Lim DW, Kim JW, Kim HS, et al. Damping index of Doppler hepatic vein waveform to assess the severity of portal hypertension and response to propranolol in liver cirrhosis: a prospective nonrandomized study. Liver Int 2007 Oct;27(8):1103-1110. 8. Piscaglia F, Gaiani S, Gramantieri L, Zironi G, Siringo S, Bolondi L. Superior mesenteric artery impedance in chronic liver diseases: relationship with disease severity and portal circulation. Am J Gastroenterol 1998 Oct;93(10):1925-1930. 9. Taourel P, Blanc P, Dauzat M, Chabre M, Pradel J, Gallix B, et al. Doppler study of mesenteric, hepatic, and portal circulation in alcoholic cirrhosis: relationship between quantitative Doppler measurements and the severity of portal hypertension and hepatic failure. Hepatology 1998 Oct;28(4):932-936.

10. Berzigotti A, Rossi V, Tiani C, Pierpaoli L, Zappoli P, Riili A, et al. Prognostic value of a single HVPG measurement and Dopplerultrasound evaluation in patients with cirrhosis and portal hypertension. J Gastroenterol 2011 May;46(5):687-695. 11. Tarantino G, Citro V, Conca P, Riccio A, Tarantino M, Capone D, et al. What are the implications of the spontaneous spleno-renal shunts in liver cirrhosis? BMC Gastroenterol 2009;9:89. 12. Berzigotti A, Merkel C, Magalotti D, Tiani C, Gaiani S, Sacerdoti D, et al. New abdominal collaterals at ultrasound: a clue of progression of portal hypertension. Dig Liver Dis 2008 Jan;40(1):62-67. 13. Berzigotti A, Zappoli P, Magalotti D, Tiani C, Rossi V, Zoli M. Spleen enlargement on follow-up evaluation: a noninvasive predictor of complications of portal hypertension in cirrhosis. Clin Gastroenterol Hepatol 2008 Oct;6(10):1129-1134. 14. Siringo S, Bolondi L, Gaiani S, Sofia S, Zironi G, Rigamonti A, et al. Timing of the first variceal hemorrhage in cirrhotic patients: prospective evaluation of Doppler flowmetry, endoscopy and clinical parameters. Hepatology 1994 Jul;20(1 Pt 1):66-73. 15. Zocco MA, Di SE, De CR, Novi M, Ainora ME, Ponziani F, et al. Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development. J Hepatol 2009 Oct;51(4):682-689. 16. Platt JF, Ellis JH, Rubin JM, Merion RM, Lucey MR. Renal duplex Doppler ultrasonography: a noninvasive predictor of kidney dysfunction and hepatorenal failure in liver disease. Hepatology 1994 Aug;20(2):362-369. 17. Maroto A, Gines A, Salo J, Claria J, Gines P, Anibarro L, et al. Diagnosis of functional kidney failure of cirrhosis with Doppler sonography: prognostic value of resistive index. Hepatology 1994 Oct;20(4 Pt 1):839-844. 18. Nompleggi DJ, Farraye FA, Singer A, Edelman RR, Chopra S. Hepatic schistosomiasis: report of two cases and literature review. Am J Gastroenterol 1991 Nov;86(11):1658-1664. 19. Hashiguchi M, Okamura T, Yoshimoto K, Ono N, Imamura R, Yakushiji K, et al. Demonstration of reversed flow in segmental branches of the portal vein with hand-held color Doppler ultrasonography after hematopoietic stem cell transplantation. Bone Marrow Transplant 2005 Dec;36(12):1071-1075.

20. Bolondi L, Gandolfi L, Arienti V, Caletti GC, Corcioni E, Gasbarrini G, et al. Ultrasonography in the diagnosis of portal hypertension: diminished response of portal vessels to respiration. Radiology 1982 Jan;142(1):167-172. 21. Schepis F, Camma C, Niceforo D, Magnano A, Pallio S, Cinquegrani M, et al. Which patients with cirrhosis should undergo endoscopic screening for esophageal varices detection? Hepatology 2001 Feb;33(2):333-338. 22. Zoli M, Dondi C, Marchesini G, Cordiani MR, Melli A, Pisi E. Splanchnic vein measurements in patients with liver cirrhosis: a casecontrol study. J Ultrasound Med 1985 Dec;4(12):641-646. 23. Goyal AK, Pokharna DS, Sharma SK. Ultrasonic measurements of portal vasculature in diagnosis of portal hypertension. A controversial subject reviewed. J Ultrasound Med 1990 Jan;9(1):45-48. 24. Zironi G, Gaiani S, Fenyves D, Rigamonti A, Bolondi L, Barbara L. Value of measurement of mean portal flow velocity by Doppler flowmetry in the diagnosis of portal hypertension. J Hepatol 1992 Nov;16(3):298-303. 25. Haag K, Rossle M, Ochs A, Huber M, Siegerstetter V, Olschewski M, et al. Correlation of duplex sonography findings and portal pressure in 375 patients with portal hypertension. AJR Am J Roentgenol 1999 Mar;172(3):631-635. 26. Gaiani S, Bolondi L, Li BS, Zironi G, Siringo S, Barbara L. Prevalence of spontaneous hepatofugal portal flow in liver cirrhosis. Clinical and endoscopic correlation in 228 patients. Gastroenterology 1991 Jan;100(1):160-167. 27. Berzigotti A, Gilabert R, Abraldes JG, Nicolau C, Bru C, Bosch J, et al. Noninvasive prediction of clinically significant portal hypertension and esophageal varices in patients with compensated liver cirrhosis. Am J Gastroenterol 2008 May;103(5):1159-1167. 28. Vizzutti F, Arena U, Rega L, Romanelli RG, Colagrande S, Cuofano S, et al. Performance of Doppler ultrasound in the prediction of severe portal hypertension in hepatitis C virus-related chronic liver disease. Liver Int 2007 Dec;27(10):1379-1388. 29. Bolognesi M, Sacerdoti D, Merkel C, Gerunda G, Maffei-Faccioli A, Angeli P, et al. Splenic Doppler impedance indices: influence of different portal hemodynamic conditions [see comments]. Hepatology 1996 May;23(5):1035-1040. 30. Piscaglia F, Donati G, Serra C, Muratori R, Solmi L, Gaiani S, et al. Value of splanchnic Doppler ultrasound in the diagnosis of portal hypertension. Ultrasound Med Biol 2001 Jul;27(7):893-899.

31. Sacerdoti D, Merkel C, Bolognesi M, Amodio P, Angeli P, Gatta A. Hepatic arterial resistance in cirrhosis with and without portal vein thrombosis: relationships with portal hemodynamics. Gastroenterology 1995 Apr;108(4):1152-1158. 32. Vilgrain V, Lebrec D, Menu Y, Scherrer A, Nahum H. Comparison between ultrasonographic signs and the degree of portal hypertension in patients with cirrhosis. Gastrointest Radiol 1990;15(3):218-222. 33. Sabba C, Weltin GG, Cicchetti DV, Ferraioli G, Taylor KJ, Nakamura T, et al. Observer variability in echo-Doppler measurements of portal flow in cirrhotic patients and normal volunteers. Gastroenterology 1990 Jun;98(6):1603-1611. 34. Iwao T, Toyonaga A, Oho K, Tayama C, Masumoto H, Sakai T, et al. Value of Doppler ultrasound parameters of portal vein and hepatic artery in the diagnosis of cirrhosis and portal hypertension [see comments]. Am J Gastroenterol 1997 Jun;92(6):1012-1017. 35. Blomley MJ, Lim AK, Harvey CJ, Patel N, Eckersley RJ, Basilico R, et al. Liver microbubble transit time compared with histology and Child-Pugh score in diffuse liver disease: a cross sectional study. Gut 2003 Aug;52(8):1188-1193. 36. Berzigotti A, Nicolau C, Bellot P, Abraldes JG, Gilabert R, Garcia-Pagan JC, et al. Evaluation of regional hepatic perfusion (RHP) by contrast-enhanced ultrasound in patients with cirrhosis. J Hepatol 2010 Dec 15.