Portal hypertension is a severe consequence of chronic liver diseases and is responsible for the main clinical complications of liver cirrhosis. Hepatic venous pressure gradient (HVPG) measurement is the best available method to evaluate the presence and severity of portal hypertension. Clinically significant portal hypertension is defined as an increase in HVPG to >10 mmHg. In this condition, the complications of portal hypertension might begin to appear. HVPG measurement is increasingly used in the clinical fields, and the HVPG is a robust surrogate marker in many clinical applications such as diagnosis, risk stratification, identification of patients with hepatocellular carcinoma who are candidates for liver resection, monitoring of the efficacy of medical treatment, and assessment of progression of portal hypertension. Patients who had a reduction in HVPG of ≥20% or to ≤12 mmHg in response to drug therapy are defined as responders. Responders have a markedly decreased risk of bleeding/rebleeding, ascites, and spontaneous bacterial peritonitis, which results in improved survival. This review provides clinical use of HVPG measurement in the field of liver disease.
Portal hypertension is a clinical syndrome defined by increased portal venous pressure gradient above 5 mmHg due to raised pre-, intra-, or post-hepatic resistance.
Direct measurement of portal pressure is highly invasive and no longer performed. In 1951, Myers and Taylor first used wedged hepatic venous pressure (WHVP), which estimates portal venous pressure by occlusive hepatic vein catheterization.
Nowadays, the most well documented marker for portal venous pressure is HVPG measurement. There are emerging data on the ability of HVPG to predict overall liver-related outcomes including risk for variceal hemorrhage.
This review presents the available data in the literature outlining the hemodynamic stage of liver fibrosis, methods for HVPG measurement, complications of HVPG measurement, and finally clinical applications of HVPG.
Liver biopsy is currently the standard for the assessment of hepatic fibrosis and is employed for prognostication and decision making processes. Histologically, LC is defined as a diffuse process in which the normal anatomical lobules are replaced by architecturally abnormal nodules separated by fibrous tissue.
HVPG measurement has evolved from being mainly used with diagnostic purposes to be considered a useful tool to assess the severity and prognosis of chronic liver disease and LC, including the risk of the complications such as varices bleeding, ascites, encephalopathy, or hepatorenal syndrome.
As recently highlighted,
Ripoll et al
At the non-cirrhotic stage of chronic liver disease (METAVIR F1-F3), there is no histological or clinical evidence of LC, and portal pressure is within normal range (1-5 mmHg). Compensated LC is classified based on the absence or the presence of varices and the risk of death is low.
In the normal liver, inter-connected sinusoidal network partially dissipates the pressure backup from the wedged catheter, and the WHVP is slightly lower than directly-measured portal pressure. In LC, the inter-sinusoidal communications are blocked by fibrous tissue, dissipation of pressure in the wedged vessels is insignificant and the WHVP accurately estimates portal pressure.
Patients who have severe cardiopulmonary disease, encephalopathy, or hypersensitivity to contrast dye are contraindicated in HVPG measurement. Permission and fasting for 8 hours are needed for the preparation of HVPG measurement. Equipment such as electrocardiography monitor, O2 saturation monitor, pressure recorder, pressure transducer, fluoroscopy, and ultrasonography (option) are needed. In addition, 6 French balloon catheter, puncture needle, vascular introducer, contrast dye, and local anesthetic are required for the proper measurement (
Antecubital, femoral, or right jugular veins are possible routes for insertion of catheter in HVPG measurement. In case of right jugular vein insertion, a 6 French balloon catheter is placed in the right hepatic vein through a right jugular vein puncture for measurement of the FHVP. The WHVP is measured by inflation of the balloon catheter at the right hepatic vein. Subsequently, the HVPG is determined by subtracting the FHVP from the WHVP (
Methods for accurate HVPG measurement are described
Only minor complications such as mainly transient cardiac arrhythmias, local pain, or vagal reaction have been reported and these occur infrequently (< 1% of patients) (
In the diagnosis of stage 1 compensated LC, the sensitivity and specificity of HVPG for predicting stage 1 compensated LC were 78% and 81% in 6 mmHg of HVPG, respectively.
In the study with post-liver transplant patients, there was a good correlation between liver stiffness measurement (LSM) and HVPG measurements in the overall population.
The most promising of the non-invasive tools to monitor fibrosis progression and associated portal hypertension is LSM by transient elastography.
In patients with acute variceal bleeding, the HVPG measurement provides prognostic information and therapeutic efficacy on the evolution of the bleeding episode. Most studies described that patients with variceal bleeding almost have an HVPG of >12 mmHg.
The early effects of endoscopic injection sclerotherapy (EIS) and endoscopic band ligation (EBL) on HVPG during acute bleeding have also been investigated.
The yearly incidence of variceal bleeding in cirrhosis patients is estimated at 4%, but this risk increases to 15% according to the size of varices.
In one study, HVPG was measured in 49 cirrhotic patients with varices at risk of first bleeding, continued therapy with beta-blocker or beta-blocker with isosorbide mononitrate.
Recent meta-analysis suggested that a reduction of HVPG below 12 mmHg or at least 20% from baseline reduced the risk of rebleeding and death.
Other studies have evaluated the use of acute HVPG response to beta-blocker as an alternative target instead of the reduction of HVPG at a repeat measurement in variceal bleeding prophylaxis.
Another study evaluated that EBL for the secondary prophylaxis of variceal rebleeding, combination medical therapy guided by HVPG monitoring was more effective than EBL for the secondary prophylaxis of variceal rebleeding and all non-responders would rebleed.
Preoperative portal pressure is an important predictor of hepatic decompensation in patients with cirrhosis after resection for HCC. Bruix et al
HVPG measurement has been evaluated in many prognostic studies, especially in alcoholic cirrhotics.
In patients with cirrhosis due to HBeAg-negative chronic B viral hepatitis, lamivudine monotherapy reduced HVPG especially in the presence of virologic suppression and biochemical remission.
Aside from confirmation of adequate propranolol dosing, HVPG may be needed to predict patient survival with decompensated liver cirrhosis.
It will be important to establish if a reduction in HVPG follows an improvement in liver function. If there is a survival advantage in lowering HVPG, then propranolol could be advocated for all cirrhotic patients.
HVPG measurement is safe, simple, and reproducible method to measure portal pressure. The modern paradigm considers cirrhosis as a dynamic and potentially reversible disease. It consists of two different entities, compensated and decompensated LC. Now, there are many stages in chronic liver disease. Of these stages, HVPG was more predictive of clinical decompensation of cirrhosis than histological fibrosis staging. The information obtained from HVPG may be predictive of new or recurrent bleeding and potentially can help in determining whether or not pharmacologic therapy is effective. The HVPG is the best surrogate marker in portal hypertension and should be measured in every trial involving pharmacologic therapy. In addition, patients with cirrhosis, the HVPG can predict the development of varices, ascites, encephalopathy, or other complications. A reduction in the HVPG is related to a reduction in the incidence of varices and variceal hemorrhage. Therefore HVPG measurement, besides monitoring hemodynamic effects, will mainly assess the all fields of chronic liver diseases.
This research was partly supported by Jeil Pharmaceutical CO., LTD. and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2010-0021482).
The author has no conflicts to disclose.
Area under receiver operating characteristic
endoscopic band ligation
endoscopic injection sclerotherapy
free hepatic venous pressure
hepatocellular carcinoma
hepatic venous pressure gradient
liver cirrhosis
liver stiffness measurement
model for end-stage liver disease
wedged hepatic venous pressure
Preparation of HVPG measurement.
Method for HVPG measurement. HVPG, hepatic venous pressure gradient; WHVP, wedged hepatic venous pressure; FHVP, free hepatic venous pressure.
Cases with abnormal location of HVPG catheter.
Arrhythmia (supraventricular tachycardia) is developed during catheter insertion.
Artifacts are caused by abnormal location of catheter (above) and cough (below). WHVP, wedged hepatic venous pressure; FHVP, free hepatic venous pressure.
Different stage of liver fibrosis
Classification | Stages | ||||
---|---|---|---|---|---|
METAVIR | F1-F3 | F4 | F4 | F4 | F4 |
HVPG (mmHg) | >6 mmHg | >10 mmHg | >12 mmHg | >16 mmHg | |
Clinical class | Stage 1 | Stage 2 | Stage 3 | Stage 4 | |
No cirrhosis | Compensated | Compensated | Decompensated | Decompensated | |
Varices | Variceal bleeding | Variceal bleeding | |||
Ascites | Ascites | ||||
Encephalopathy | Encephalopathy | ||||
Bacterial infection | |||||
Hepatorenal syndrome | |||||
1-yr mortality | 1% | 3% | 10-30% | 60-100% |
HVPG, hepatic venous pressure gradient.
Methods for adequate calibration and recording in the HVPG measurements
Adequate calibration and recording | |
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Use an appropriate scale. | Venous pressures have an upper range of approximately 30-40 mmHg. Therefore, scales used for arterial pressure measurements are not adequate. To be able to detect small changes, the scale should be set at 1 mmHg = 1 mm on the scale |
Use slow recording speed. | Stabilization of venous pressures should be evaluated over a period of approximately 1 min for WHVP or 15 seconds for FHVP. The appropriate speed is 5 mm/second, optimally 1-2 mm/second. Note that in a “normal” ECG with a speed of 25 mm/second, one page of tracing includes approximately 10 seconds of measurement and this is not adequate for accurate interpretation of the tracing. |
Check the accuracy of the transducer calibration by obtaining tracings of a known external pressure. | If a transducer does not calibrate exactly against a known external pressure, replace it. |
Place the transducer at the level of the right atrium (mid-axillary line). | The intravascular pressures will read higher if the transducer is lowered, but they will decrease if the transducer is raised. Record the IVC pressure on the tracing at the level of the liver (hepatic veins) before catheterizing the hepatic vein. Catheterize preferably the main right hepatic vein. |
This table is quoted from the table of reference
HVPG, hepatic venous pressure gradient; WHVP, wedged hepatic venous pressure; FHVP, free hepatic venous pressure; ECG, electrocardiogram; IVC, inferior vena cava.
Methods for accurate and reliable HVPG measurement
Actual measurement | |
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1. | Do not advance the catheter too far into the hepatic vein when measuring the pressure. The FHVP should not be more than 1 mmHg greater than the IVC pressure. Greater differences require withdrawal of the catheter closer to the IVC for an accurate measurement of FHVP. |
2. | Record the tracing for 45–60 seconds to allow the measure to stabilize. Also, continue recording when deflating the balloon to recheck the FHVP. |
3. | Obtain a mean pressure. |
4. | Repeat measurements at least three times to make sure that values obtained are reproducible. If they are not, check the wedged position of the catheter. |
5. | Check the inflated balloon for total occlusion of the hepatic vein ( |
6. | If the patient is pre-medicated, for comparative purposes, subsequent measurements should be performed under the same conditions. |
7. | Register on tracing ongoing events. For example, cough or slight movements cause artifacts that may give inaccurate readings ( |
8. | Never rely on digital readings on the screen. These are instantaneous readings and may not be representative of the correct measurement. |
This table is quoted from the table of reference.
HVPG, hepatic venous pressure gradient; WHVP, wedged hepatic venous pressure; FHVP, free hepatic venous pressure; ECG, electrocardiogram; IVC, inferior vena cava.