The Vienna General Hospital and the Medical University of Vienna kindly provides the infrastructure for the Vienna Hepatic Hemodynamic Laboratory. Previous members of the Vienna Hepatic Hemodynamic Laboratory and coworkers should be acknoweledged for their valuable input that helped to continuously improve the methodology of HVPG measurement and transjugular liver biopsy at our institution. In addition, we thank the nurses of the Division of Gastroenterology and Hepatology who are an essential part of the Vienna Hemodynamic Laboratory and continuously provide patients with excellent care.

The protocol described here complies with the guidelines of the human research ethics committee of the Medical University of Vienna.
1. Preparations
<ol>
	<li>Use a specialized room dedicated/approved for procedures using x-ray equipped with a digital x-ray fluoroscopy&#160;system (Figure 1A), a monitor system (Figure 1B), a pressure recorder and transducer (Figure 1<st...

While HVPG measurements require considerable resources and trained personal with interventional skills and expertise in the reading of pressure tracings, it improves prognostication and might guide treatment decisions, and thus, facilitates personalized medicine. In addition, the opportunity to safely obtain liver biopsy specimens via the transjugular route in the same session is another argument in favor of implementing hepatic hemodynamic laboratories at tertiary care centers. Indeed, guidelines support the use of HVPG...

Patients with cirrhosis are at risk for developing complications mostly related to portal hypertension (PHT), such as ascites or bleeding from gastric or esophageal varices1,2,3. The risk of hepatic decompensation is related to the degree of PHT2. Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard to estimate portal venous pressure in patient with cirrhosis, i.e. assessing the severity of sinusoidal&#160;portal hypertension4. An HVPG of &#8805;6 mm Hg to 9 mm Hg indicates elevated portal pressure (&#39;subclinical portal hypertension&#39;), while an HVPG &#8805;10 mm Hg defines CSPH. This protocol provides a detailed description of the equipment and the procedure and also highlights potential pitfalls and offers advice for troubleshooting.
Clinically, measurement of HVPG is indicated (i) to establish the diagnosis of sinusoidal&#160;portal hypertension, (ii) to identify patients at risk for hepatic decompensation by diagnosing CSPH (HVPG &#8805;10 mm Hg), (iii) to guide pharmacological therapy in primary or secondary prophylaxis of variceal bleeding, and (iv) to assess the risk of hepatic failure after partial hepatectomy2,4. HVPG is used as an established surrogate marker for improvement and/or worsening of liver fibrosis/function, since a decrease in HVPG translates into a clinically meaningful benefit5, whereas higher HVPG values are associated with an increased variceal bleeding risk6. Based on observations on changes in HVPG in patients under non-selective beta-blocker (NSBB) or etiological therapies, a decrease in HVPG of 10% is considered to be clinically relevant7,8.
To date, there are no alternative, non-invasive parameters reflecting the degree of portal pressure with similar accuracy as HVPG. Even if HVPG is actually an &#8216;indirect&#8217; way to measure portal pressure, it strongly correlates and thus accurately reflects &#8216;directly&#8217; measured portal pressure in patients with cirrhosis9. Importantly, HVPG measurements should be performed using a balloon catheter to maximize the assessed amount of liver parenchyma10,11,12. Although HVPG measurements are invasive, resource-intensive, and require interventional skills and expertise in interpreting the reliability and plausibility of pressure readings, this method is the current gold standard for diagnosing and monitoring portal hypertension in patients with cirrhosis13,14,15.
Simple laboratory values, such as platelet count, may help to estimate the likelihood for CSPH. However, platelet count, or non-invasive scores that include platelet count, have limited predictive value16. Imaging modalities showing splenomegaly17 or portosystemic collaterals18 in patients with cirrhosis suggest the presence of CSPH, but are not helpful for quantifying the actual degree of portal hypertension. Novel non-invasive imaging tools, such as elastography of the liver19 and/or of the spleen20 are useful for ruling-in or ruling-out the presence of CSPH. Still, none of the available methods is able to directly measure dynamic changes in portal pressure21.
The prognostic value of HVPG has been underlined by several landmark studies, showing that a HVPG &#8805;10 mm Hg (i.e. CSPH) is predictive for the formation of varices8 (and for the development of complications related to portal hypertension22, while a (pharmacologically-induced) decrease of HVPG modulates the respective risk of variceal growth23 and decompensation7. HVPG-response is the only established surrogate for the effectiveness of NSBBs in preventing (recurrent) variceal bleeding. If HVPG decreases to a value of &#8804;12 mm Hg or is reduced by &#8805;10-20% during NSBB treatment, patients are protected from variceal bleeding and survival is increased24,25. Similarly, HVPG-response also decreases the incidence of ascites and related complications in patients with compensated cirrhosis5,26. Several studies have provided evidence supporting the use of HVPG-guided therapy27,28,29,30,31,32. Thus, in centers with sufficient experience, HVPG-response may&#160;guide treatment decisions, facilitating personalized medicine for patients with portal hypertension.
Moreover, measuring of HVPG might serve as a surrogate endpoint for proof-of-concept studies assessing the effectiveness of novel treatments for cirrhosis and/or portal hypertension being translated from bench to bedside, such as sorafenib33,34, simvastatin35,36, taurine37, or emricasan38. Ultimately, measurements of HVPG can also provide important prognostic information about the risk for development of HCC39 and for liver failure post hepatic resection40.
The infrastructure to measure HVPG should be readily available at secondary and tertiary care centers. Since the technique of HVPG measurement requires specialized training and equipment, it seems rational for academic and transplant centers to establish a hepatic hemodynamic laboratory, facilitating state-of-the-art diagnosis and management of portal hypertension. Large volume centers perform several hundred HVPG measurements per year. Based on our experience, sufficient expertise to perform accurate HVPG measurements is usually obtained after 50-100 supervised HVPG measurements.

<table border="0" cellpadding="0" cellspacing="0" style="width:1628px;" width="1627">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:315px;">10 mL Luer-Lock syringe</td>
			<td style="width:335px;">Braun</td>
			<td style="width:317px;">REF 4617100V, LOT 17G03C8</td>
			<td style="width:661px;">Luer-Lock Syringe for connection with the aspiration biopsy set</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">10 mL Syringe 2x</td>
			<td>Braun</td>
			<td style="width:317px;">REF 4606108V</td>
			<td>Snonpyrogenic, nontoxic 10 mL syringe</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">10 F liver biopsy&#160; introducer sheath set</td>
			<td>Cook Medical</td>
			<td style="width:317px;">REF RCFW-10.0-38, REF G07600</td>
			<td>Percutaneous Sheath Introducer Set (TJBX), 10F Port, 13cm, Check-Flo Performer Introducer</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">18 G needle for biopsy introducer sheat</td>
			<td>Arrow International</td>
			<td style="width:317px;">REF AN-04318</td>
			<td>Introducer Needle for TJBX Set, 18 G, 6.35 cm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">21 G needle</td>
			<td>Henke Sass Wolf</td>
			<td style="width:317px;">REF 0086, Fine-Ject 21Gx2&#34;</td>
			<td>Sterile injeciton needle, 21 Gx2&#34;, 0.8 x 50 mm, for local anesthesia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">3-way channels</td>
			<td>Becton Dickinson</td>
			<td style="width:317px;">BD Connecta Luer-Lok, REF 39402</td>
			<td>Three way channel with Luer-Lok connection system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">7.5 F catheter introducer sheath set</td>
			<td>Arrow International</td>
			<td style="width:317px;">REF SI_09875-E</td>
			<td>Percutaneous Sheath Introducer Set, 7.5 F Port</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Aspiration TJLBX set</td>
			<td>Cook Medical</td>
			<td style="width:317px;">REF RMT-16-51.0-TJL, REF G20521</td>
			<td>TJ Liver Access and Biopsy Needle Set (Aspiration Set), 9 F-45 cm, 16 G-50.5 cm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Balloon catheter</td>
			<td>Gerhard Pejcl Medizintechnik Austria</td>
			<td style="width:317px;">REF 500765B</td>
			<td>Ferlitsch HVPG Catheter, 7F-65cm, Balloon:2.5mL, Pressure 50-90 kPa, GW: 0.032&#34;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Blade 11 scalpel</td>
			<td>Medi-Safe Surgicals</td>
			<td style="width:317px;">MS Safety Scalpel REF /Batch 18012424</td>
			<td>11 blade safety scalpels, retractable, single use, 10 scalpels per package</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Blunt tip fill needle</td>
			<td>Becton Dickinson</td>
			<td style="width:317px;">REF 303129</td>
			<td>Sterile blunt tip fill needle, single use</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Contrast media (dye)</td>
			<td>Dr. Franz K&#246;hler Chemie GmbH, Bensheim, GER</td>
			<td style="width:317px;">ZNR 1-24112</td>
			<td>Peritrast 300 mg Iod/mL, 50 mL, contrastmedia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Core TJLBX set</td>
			<td>Cook Medical</td>
			<td style="width:317px;">REF RMT-14XT-50.5-LABS-100, REF G08285</td>
			<td>TJ Needle Introducer and Bx-Needle 7 F-53.5 cm, 14 G-53.5 cm/20 mm, 18 G-60 cm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Digital x-ray fluoroscope system</td>
			<td>Siemens</td>
			<td style="width:317px;">Model No 07721710</td>
			<td>ARCADIS Varic, mobile x-ray fluoroscope system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Disinfectant solution</td>
			<td>Gebro Pharma</td>
			<td style="width:317px;">1-20413</td>
			<td>Isozid-H</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Face mask</td>
			<td>MSP Medizintechnik GmbH</td>
			<td style="width:317px;">REF HSO36984</td>
			<td>Surgical face mask from double fleece, with tie, 50 pieces</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Guide wire for biopsy introducer sheat</td>
			<td>Arrow International</td>
			<td style="width:317px;">REF AW-14732</td>
			<td>Marked Spring-Wire Guide, TJBX Set, 0.032&#34;, 0.81 mm, 68 cm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Infusion line</td>
			<td>Rosstec Medical Products b Cardea GmbH &#38; Co</td>
			<td style="width:317px;">REF 220010, 100m</td>
			<td>Infusion line, Luer-Lok for connection of balloon catheter and pressure transducer</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Lidocaine 2%</td>
			<td>Gebro Pharma</td>
			<td style="width:317px;">Xylanaest, ZNR 17.792, 20mg/1mL (2%)</td>
			<td>Sterile vials Xylanest including 2% Lidocain hydrochloride for local anesthesia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Midazolame</td>
			<td>Roche</td>
			<td style="width:317px;">Dormicum, ZNr 1-18809, Midazolam 5mg/5mL</td>
			<td>Sterile vials Dormicum including Midazolam for sedation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Monitor system</td>
			<td>Datex-Ohmeda by GE</td>
			<td style="width:317px;">Type F-CMREC1</td>
			<td>Patient monitoring system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Patient bench</td>
			<td>Silerlen-MAQET</td>
			<td style="width:317px;">Model No 7474.00A</td>
			<td>Mobile patient bench for x-ray fluoroscopy</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Pressure bag</td>
			<td>Ethox Corp</td>
			<td style="width:317px;">REF 4005</td>
			<td>Pressure Infuser Bag 500 mL</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Pressure recorder</td>
			<td>Edwards Lifesciences</td>
			<td style="width:317px;">Ref T001631A, Lot 61202039</td>
			<td>TruWave 3 cc/150 cm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Pressure transducer</td>
			<td>Edwards Lifesciences TM</td>
			<td style="width:317px;">REF T001631A</td>
			<td>Pressure Monitoring Set (1x), 3 cc/150 cm, TruWave TM</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;">Recording software&#160;</td>
			<td>Datex Ohmeda by GE</td>
			<td style="width:317px;">Software S/5 is property of Instrumentarium Corp of Datex-Ohmeda TM</td>
			<td>Datex-Ohmeda S/5TM Collect - Software to record pressure tracings of the patient monitor system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile coat</td>
			<td>Lohmann &#38; Rauscher International GmbH &#38; Co</td>
			<td style="width:317px;">REF 19351</td>
			<td>Surgical Gown, Different sizes, e.g. L-130 cm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile gauze</td>
			<td>Hartmann</td>
			<td style="width:317px;">REF 401798, 10x10cm gauze</td>
			<td>10 x 10 cm sterile gauze, 10 pieces per package</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile gloves</td>
			<td>Meditrade</td>
			<td style="width:317px;">REF 9021</td>
			<td>Gentle Skin sterile gloves, different sizes, e.g. 7.5</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile saline solution</td>
			<td>Fresenius Kabi</td>
			<td style="width:317px;">NaCl 0.9%, B009827 REV 03</td>
			<td>Physiologic Saline Solution 0.9% NaCl, 309 mosmol/L, pH-Wert: 4.5-7.0</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile saline vessel</td>
			<td>KLS Martin</td>
			<td style="width:317px;">REF K8A,&#160; 18/10 Jonas</td>
			<td>Sterilizable Metal Vessel for sterile saline</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile table cover</td>
			<td>Hartmann</td>
			<td style="width:317px;">REF 2502208</td>
			<td>Table Cover, Foliodrape 150 x 100 cm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile towel</td>
			<td>BARRIER by M&#246;lnlycke Health Care</td>
			<td style="width:317px;">REF 706900</td>
			<td>Adhesive OP-Towel, 100 x 100 cm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile US probe cover sheath</td>
			<td>Websinger</td>
			<td style="width:317px;">REF 07014</td>
			<td>Sterile ultrasound probe cover, 20 x 60 cm, inluding two sterie adhesive tapes</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Stiff guidewire</td>
			<td>Cook Medical</td>
			<td style="width:317px;">REF TSMG-35-180-4-LES, G46729</td>
			<td>Lunderquist Extra Stiff Wire Guide, 0.035&#34;-.89 mm, 180 cm, 4 cm flexible tip</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Surgical cap</td>
			<td>BARRIER by M&#246;lnlycke Health Care</td>
			<td style="width:317px;">REF 620500, PCS 100, Colour Green</td>
			<td>Surgical Cap</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Ultrasound device</td>
			<td>FUJIFILM SonoSite</td>
			<td style="width:317px;">Model M-Turbo, REF P17000-17</td>
			<td>Mobile ultrasound system</td>
		</tr>
	</tbody>
</table>

measurement of the hepatic venous pressure gradient and transjugular liver biopsy

Here we provide a detailed protocol describing the clinical procedure of hepatic venous pressure gradient (HVPG) measurement in patients with advanced chronic liver disease followed by an instruction for transjugular biopsy. Under local anesthesia and ultrasound guidance, a catheter introducer sheath is placed in the right internal jugular vein. Using&#160;fluoroscopic guidance, a balloon catheter is advanced into the inferior vena cava (IVC) and inserted into a large hepatic vein. Correct and sufficient wedge position of the catheter is ensured by injecting contrast media while the balloon is blocking the outflow of the cannulated hepatic vein. After calibrating the external pressure transducer, continuous pressure recordings are obtained with triplicate recordings of the wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP). The difference between FHVP and WHVP is referred to as HVPG, with values &#8805;10 mm Hg indicating clinically significant portal hypertension (CSPH). Before removing the catheter, pressure readings obtained in the IVC at the same level, as well as the right atrial pressure are recorded.
Finally, a transjugular liver biopsy can be obtained via the same vascular route. Different systems are available; however, core biopsy needles are preferred over aspiration needles, especially for cirrhotic livers. Again, under fluoroscopic guidance a biopsy needle introducer sheath is advanced into an hepatic vein. Next, the transjugular biopsy needle is gently advanced through the introducer sheath: (i) in case of aspiration biopsy, the needle is advanced into the liver parenchyma under aspiration and then removed quickly, or (ii) in case of a core biopsy, the cutting-mechanism is triggered inside the parenchyma. Several separate passages can be safely performed to obtain sufficient liver specimens via transjugular biopsy. In experienced hands, the combination of these procedures takes about 30-45 min.

In compensated patients with well-preserved liver function (i.e. without any history of hepatic decompensation, such as ascites or variceal bleeding) the measured HVPG values might be normal or in the range of subclinical portal hypertension (HVPG 6&#8211;9 mm Hg). However, compensated patients might develop CSPH (HVPG &#8805;10 mm Hg) which indicates an increased risk for developing varices or hepatic decompensation. In turn, patients with esophageal or gastric varices, HVPG is usually in the range of CSPH, if not patie...

Watch this Scientific Journal Video about Measurement of the Hepatic Venous Pressure Gradient and Transjugular Liver Biopsy at JoVE.com

Measurement of the Hepatic Venous Pressure Gradient and Transjugular Liver Biopsy

Here, we present a protocol for measurement of hepatic venous pressure gradient (HVPG),the gold standard to diagnose clinically significant portal hypertension. Moreover, we describe how to perform a transjugular liver biopsy within the same session.

Here we provide a detailed protocol describing the clinical procedure of hepatic venous pressure gradient (HVPG) measurement in patients with advanced ...

Diagnosing portal hypertension in patients with advanced chronic liver disease has important prognostic implications. Assessing the severity and treatment response allows for individualized treatment approaches in these patients. Measurement of the hepatic venous pressure gradient, or HVPG, is the gold standard for diagnosing of portal hypertension in patients with advanced chronic liver disease.The prognostic value of HVPG and the clinical benefits of a decrease in HVPG have been established over a broad spectrum of etiologies of advanced chronic liver disease and also disease severity. HVPG measurement provides important insights into the complex interplay between portal hypertension and the related pathophysiological mechanisms that drive the development of clinical events in cirrhosis. Before placement, flush the balloon catheter with contrast medium and inflate and deflate the balloon several times with the catheter tips submerged in saline to check the integrity of the instrument.No air bubbles should occur. Moisten the outside of the balloon catheter with additional sterile saline solution before inserting the catheter into the vascular access sheath. Advance the catheter under fluoroscopic guidance into the inferior cava vein, or IVC, using slight rotations to align the tip of the catheter toward the back of the patient to advance from the right atrium to the IVC.To advance the catheter from the IVC into the hepatic vein, repeatedly moved the tip of the balloon catheter to the right toward the suspected area of the junction of the hepatic veins and the IVC to obtain access to the hepatic veins. Advance the catheter to a stable position that allows repeat measurement of the free hepatic venous pressure at a two to four centimeter distance from the opening of the junction into the IVC with sufficient space for the inflated balloon. Confirming its efficient wedge position of the balloon catheter in the hepatic vein is critical for obtaining reliable readings.This is confirmed by dye injection and the fluoroscopy. To check the adequacy of the vein occlusion, inflate the balloon with about two milliliters of air and about five milliliters of contrast dye until the hepatic vein distal to the inflated balloon can be visualized. Observe the stasis of the contrast medium and exclude any wash out due to insufficient occlusion of the venous lumen by the balloon or the presence of shunts.Then deflate the balloon and flush the lumen of the catheter with saline. To assess the hepatic venous pressure gradient, use an infusion line to connect to the vascular lumen of the balloon catheter to the pressure transducer and begin recording the free hepatic venous pressure with the tip of the balloon two to four centimeters from the opening of the hepatic vein to the IVC. The wave form of the curve of the free hepatic venous pressure gradient might show slight oscillations related to the heartbeat.Inflate the balloon and continue recording the wedge hepatic venous pressure until the measurement becomes a stable horizontal line with no variations over time. After repeating the free and wedge hepatic venous pressures at least three times record pressure in the IVC at the level of the ostium of the hepatic vein as well as the right atrial pressure. Before beginning the biopsy procedure, flush the biopsy needle introducer sheath with sterile saline.Check the system for smooth access and advance the biopsy needle introducer sheath into a hepatic vein as demonstrated for the balloon catheter. Gently advance the 16 gauge needle through the biopsy needle introducer sheath into the hepatic vein. To load the transjugular core liver biopsy needle, pull the grip until the shooting mechanism is loaded.Advance the core biopsy set through the biopsy needle until the tip of the core biopsy set approaches the end of the biopsy needle in the hepatic vein. Instruct the patient to hold their breath and advance the core biopsy set into the liver parenchyma. Pull the trigger of the shooting mechanism to perform the core biopsy and advise the patient to breathe normally.Remove the needle without removing the needle introducer sheath and harvest the liver sample. When all of the biopsies have been obtained inject five to 10 milliliters of contrast medium over the catheter introducer sheath to rule out perforation of the liver capsule and remove the biopsy needle introducer sheath. In a cirrhotic patient with varices or with portal hypertensive ascites, the HPVG values are expected to be at least greater to or equal to 10 millimeters of mercury.In this example, the continuous green line indicates the recorded free hepatic venous pressure of five millimeters of mercury and discontinuous red line indicates the recorded wedged hepatic venous pressure of 26 millimeters of mercury. Thus, the calculated hepatic venous pressure gradient in this patient is 21 millimeters of mercury which indicates clinically significant portal hypertension Major complications of HVPG measurement and transjugular liver biopsy are rare and mainly related to the central venous access. Here, the use of ultrasound guided central venous access will largely reduce the risk of these complications.Adequate training of central venous access development is critical to reduce the risk of major complications of HPVG measurement. Non-invasive tests are not sufficiently accurate for assessing the severity of portal hypertension in patients with CSPH and have limited accuracy for monitoring the evolution of portal hypertension after etiologically and medical therapies.

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Research

JoVE Journal

Medicine

18.4K vistas.  Medical University of Vienna. Diagnosing portal hypertension in patients with advanced chronic liver disease has important prognostic implications. Assessing the severity and treatment response allows for individualized treatment approaches in these patients. Measurement of the hepatic venous pressure gradient, or HVPG, is the gold standard for diagnosing of portal hypertension in patients with advanced chronic liver disease.The prognostic value of HVPG and the clinical benefits of a decrease in HVPG have been esta...